Section 2 Insecticides

*Trends in Integrated Insect Pest Management*

seeding beech (*Fagus sylvatica*) patches.

[38] Rastegar J, Sakenin H, Khodaparast SH, Havaskary M. On a collection of Braconidae (Hymenoptera) from East Azarbaijan and vicinity, Iran. Calodema.

[39] Zargar M, Talebi AA, Hajghanbar H, Papp J. A study on the genus *Bracon fabricius* (Hymenoptera: Braconidae) in North Central Iran with four new records for Iranian fauna. Entomofauna:

[40] Guler Y, Cagatay N. Systematical

Zeitschrift fur Entomologie.

studies on the genus *Bracon (Glabrobracon)* (Hymenoptera, Braconidae: Braconinae) in Ankara province. Turkish Journal of Zoology.

2015;**36**(32):425-440

2001;**25**:275-286

[37] Oboyski PT. The Systematics, Evolution, and Ecology of Hawaiian Cydia (Lepidoptera: Tortricidae) [thesis]. Berkeley: University of

Ecology. 1987;**68**:260-265

California. 2011; 123 pp

2012;**226**:1-4

[29] Elzinga JA. The effects of habitat fragmentation on a tri-trophic system: *Silene latifolia*, *Hadena bicruris* and its parasitoids [thesis]. Netherlands: Utrecht University; 2005. 184 pp

[30] Elzinga JA, Nouhuys S, Leeuwen DJ, Biere A. Distribution and colonization ability of three parasitoids and their herbivorous host in a fragmented landscape. Basic and Applid Ecology.

[31] Valipour J, Vahedi HA, Zamani AA. An outline on biology and behavior of *Bracon variator* Nees, 1812 (Hym.: Braconidae), an ectoparasitoid of *Cydia johanssoni* Aarvik and Karsholt, 1993 (Lepidoptera: Tortricidae) from Iran. Biharean. Biologist. 2017;**11**(1):15-19

[32] Valipour J, Vahedi HA, Zamani AA. Preliminary morphological study of developmental stages of *Cydia johanssoni* Aarvik and Karsholt (Lep: Tortricidae) on the stinking bean trefoil, *Anagyris foetida* L. (Leguminosae) in Iran. Journal of Applied Environmental and Biological Sciences. 2015;**5**(7):299-304

[33] Ramirez N, Traveset A. Predispersal

[34] Zhang J, Drummond FA, Liebman M, Hartke A. Insect predation of seeds and plant population dynamics. Maine Agricultural and Forest Experiment Station Technical Bulletin. 1997;**163**

[35] Nielsen BO. Beech seeds as an ecosystem component. Oikos.

[36] Nilsson SG, Wastljung U. Seed predation and cross pollination in mast

1977;**29**:268-274

seed-predation by insects in the Venezuelan central plain: Overall patterns and traits that influence its biology and taxonomic groups. Perspectives in Plant Ecology, Evolution and Systematics. 2010;**12**(3):193-209

2005;**14**:1-14

Ichneumonoidea). Zoologische Verhandelingen Leiden. 1990;**258**:1-95

**16**

**19**

**Chapter 2**

**Abstract**

**1. Introduction**

*domestica*

Defence against Oxidative

Stress and Insecticides in *Musca* 

This review is looking at the way *Musca domestica* defends itself against harmful molecules. One of the most notable enemies is against oxidative stress. Over the years there were reports that indicated the development of resistance on range of pesticides that are used against the flies. Researches have demonstrated that there are several functional protein molecules which contribute directly or indirectly as a response to oxidative stress and resistance against insecticides. As currently, the whole genome sequencing of the organisms has enabled future study to be conducted in evaluating the behaviour of the targeted protein/enzyme in response to

An estimated 150,000 of species of Diptera have been described [1], and houseflies (*Musca domestica*) are one of the wonderfully evolved organism. A notorious vector, houseflies are associated with more than 100 pathogens [2], and resistance towards insecticides of houseflies have been reported all over the world. According to Scott et al., *Musca domestica* is suitable as a model organism for resistance studies and development of new insecticides. The knowledge on cellular metabolism in recent years has been expanded to understand the metabolic aspect of oxidative stress. In *Musca domestica* alone, a few families of proteins have been more or less associated with oxidative stress response: glutathione S-transferases (GST) [3–5],

Naturally houseflies' main ecosystem role is to decompose and recycle organic material. Houseflies are synanthropic insect in urban areas where high densities of human waste are their food source [10, 11]. It has been known to be vectors of various diseases of over 30 bacteria, protozoan, viruses and helminth eggs [12]. It also transfers viruses such as polioviruses [13] and *Coxackie* viruses, as well as numerous bacteria such as *Campylobacter jejuni*, *Helicobacter pylori* [14], *Salmonella* sp. [14], *Listeria* sp., *Yersinia pseudotuberculosis* [15], *Shigella* sp. [16], *Escherichia coli* [17], and *Vibrio* sp. [13]. Flies may also be vectors of protozoan flies such as *Giardia* and

*Tan Yong Hao, Siti Nasuha Hamzah and Zazali Alias*

oxidative stress and intake of insecticides in the flies.

**Keywords:** *Musca domestica*, oxidative stress, insecticide resistance

superoxide dismutase (SOD) [6] and glutathione peroxidases [7–9].

**2.** *M. domestica* **response towards insecticide**

## **Chapter 2**

## Defence against Oxidative Stress and Insecticides in *Musca domestica*

*Tan Yong Hao, Siti Nasuha Hamzah and Zazali Alias*

## **Abstract**

This review is looking at the way *Musca domestica* defends itself against harmful molecules. One of the most notable enemies is against oxidative stress. Over the years there were reports that indicated the development of resistance on range of pesticides that are used against the flies. Researches have demonstrated that there are several functional protein molecules which contribute directly or indirectly as a response to oxidative stress and resistance against insecticides. As currently, the whole genome sequencing of the organisms has enabled future study to be conducted in evaluating the behaviour of the targeted protein/enzyme in response to oxidative stress and intake of insecticides in the flies.

**Keywords:** *Musca domestica*, oxidative stress, insecticide resistance

## **1. Introduction**

An estimated 150,000 of species of Diptera have been described [1], and houseflies (*Musca domestica*) are one of the wonderfully evolved organism. A notorious vector, houseflies are associated with more than 100 pathogens [2], and resistance towards insecticides of houseflies have been reported all over the world. According to Scott et al., *Musca domestica* is suitable as a model organism for resistance studies and development of new insecticides. The knowledge on cellular metabolism in recent years has been expanded to understand the metabolic aspect of oxidative stress. In *Musca domestica* alone, a few families of proteins have been more or less associated with oxidative stress response: glutathione S-transferases (GST) [3–5], superoxide dismutase (SOD) [6] and glutathione peroxidases [7–9].

## **2.** *M. domestica* **response towards insecticide**

Naturally houseflies' main ecosystem role is to decompose and recycle organic material. Houseflies are synanthropic insect in urban areas where high densities of human waste are their food source [10, 11]. It has been known to be vectors of various diseases of over 30 bacteria, protozoan, viruses and helminth eggs [12]. It also transfers viruses such as polioviruses [13] and *Coxackie* viruses, as well as numerous bacteria such as *Campylobacter jejuni*, *Helicobacter pylori* [14], *Salmonella* sp. [14], *Listeria* sp., *Yersinia pseudotuberculosis* [15], *Shigella* sp. [16], *Escherichia coli* [17], and *Vibrio* sp. [13]. Flies may also be vectors of protozoan flies such as *Giardia* and

*Entamoeba* [16] and eggs of several tapeworms [18]. In 2010, there were further proof on transmission of Newcastle disease virus (NDV—*Paramyxoviridae*), a highly infectious virus shed in the faeces in infectious birds [19] with *Musca domestica* as vector in both field and laboratory. More recently, *Musca domestica* were also reported to carry antibiotic-resistant bacteria such as methicillin-resistant *Staphylococcus* and ticarcilin-resistant *Pseudomonas* [20], which possess threat in hospitals and healthcare facilities [18]. Flies are causing 6 million cases of childhood blindness each year (http://www.who.int/topics/trachoma/en/). *Musca domestica* also create implications in economical ways, and costs of pesticides were estimated at more than US\$200 million yearly in the United States [21] and US\$1.6 million in 1998 [22].

The types of insecticides used to control houseflies on field are adulticides and larvicides (www.flycontrol.norvatis.com). Adulticides are carbamates (e.g. propoxur and methomyl), organophosphates (e.g. fenitrophon, azamethiphos and dimethoate), pyrethroids (e.g. cyfluthrin, deltamethrin and permethrin) and recently neonicotinoids (e.g. imidacloprid, thiamethoxam). Larvicides are insect growth regulators (IGRs) (e.g. triflumuron, diflubenzuron, cyromazine [23], and novaluron and juvenile hormone synthetic analogues (e.g. methoprene, fenoxycarb, pyriproxyfen [23] (www.flycontrol.novartis.com). Since the first case of DDT resistance is reported on the housefly [24], resistance of adult *Musca domestica* towards various insecticides in various sites (agricultural, wild and urban) is a fast-growing global issue. There has been an increasing resistance profile report from various places in the world.

In the United Kingdom, a resistance risk assessment done by [25] showed that although farmers claimed they had reduced using insecticides (a measure to reduce selective stress on field housefly strains), there was no sign of decrease of housefly resistance towards piperonyl butoxide synergized pyrethrins. Flies with high fenitrothion and dimethoate resistance were also discovered in Denmark [26]. In 1997, an increase in pyrethroid-resistant strains and widespread of azamethiphosresistant strains in 21 different farms all over Denmark were confirmed [27]. In Argentina, a first insecticide survey was reported [28]. Several *Musca domestica* populations were found to be permethrin-, dichlorovinyl dimethyl phosphate (an organophosphate)- and cyromazine-resistant. In the neighbouring Brazil, [29] led a first evaluation of cyromazine resistance of houseflies in five different sites, and three out of the five sites indicated cyromazine resistance. There was a report suggesting the occurrence of insecticide tolerance in tsunami-hit villages in India [30]. With hygiene at minimum provision, immediate fly control was imposed by spraying 76% dichlorvos, and LD90 of adult housefly was 3.5–3.9 times higher than the flies from control sites. As in the United States, in a study tested against nine insecticides, the fly strains showed high resistances in tetrachlorvinphos, permethrin and cyfluthrin [31], while in southeastern Nebraska, houseflies are shown to be moderately resistant to permethrin yet extremely resistant to stirofos and methoxychlor [32]. Deltamethrin-resistant flies were discovered in urban garbage dump of cities of Beijing, Tianjin and Zhangjiakou [33].

In Malaysia, [34] resistance of housefly from a garbage dump, poultry farm and agricultural farm was evaluated. It was shown that garbage dump and poultry farm fly samples were more resistant than agricultural farm. It was also shown that two poultry farms in the state of Penang against malathion, propoxur and DDT, with resistance ratio, have been found with strong correlations against relative humidity, which is a first in field discovery [35]. However, on housefly larvae, resistance assessment has been relatively scarce with only a handful of feeding and toxicity tests done. A report on an increase in diflubenzuron resistance and new-found cyromazine resistant strain was also obtained [36]. A dip test-emergence test of *Musca domestica* third instar larvae on eucalyptol extracts has been done [37] with LD50 values of 118 mg/fly and 177 mg/fly on male and female flies, respectively.

**21**

*Defence against Oxidative Stress and Insecticides in* Musca domestica

In an oxidative stress-induced insecticide resistance research, rats [38–40], humans [41], fresh water fish *Brycon cephalus* [42] and black tiger shrimp *Penaeus monodon* [43] have been used as models to investigate insecticide inflicted oxidative stress. Insecticides including pyrethroids [44, 45], organophosphates [46–48] and organochlorines [49] have known to be inducing oxidative stress. It was reported that there were changes in activities of the antioxidative enzymes such as superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase and in GSH level changes both in the liver and erythrocyte homogenate [39]. Molecular resistances are consisted of target site resistance and metabolic-based resistance [50]. Yet, most of the works, as far as *Musca domestica* is concerned, have been more in top-down approach. While genome sequencing was still ongoing for that time being, specific gene family is identified and sequenced before getting into expression studies. With other fly species such as the dipteran *Drosophila melanogaster* and *Anopheles* genome as comparable reference database, it was also concluded three groups of gene superfamilies are involved in metabolic-based resistance [51], i.e.

glutathione S-transferases, cytochrome P450 and acetylcholinesterase.

of resistances of P450, GSTs, and acetylcholinesterases [56, 57].

It was suggested that aerobic organisms survive due to their evolved antioxidant

capability [58]. Catalase (EC 1.11.1.6) was discovered in tobacco extracts [59]. Catalase detoxifies H2O2 into water and oxygen [60]. Catalase is one of the welldescribed enzymes, and it is a class of enzyme including the iron-heme enzyme, catalase-peroxidases and a small group of manganese enzymes [61]. Superoxide dismutase (EC 1.15.1.1) is a well-known enzyme against oxidative stress. SOD1, the first superoxide dismutase to be identified, uses free radical as a substrate [62]. A metalloenzyme, superoxide dismutase catalyses the dismutation of superoxide anion (O2<sup>−</sup>) to hydrogen peroxide and oxygen, as the first defence line against oxidative stress [63]. They are also known to exhibit additional peroxidase activity when hydrogen peroxide level is at its large. It has been suggested that the removal of superoxide

**3.1 Enzymatic removal of cellular hydrogen peroxide**

In cytochrome P450, [52] it was revealed that three P450 genes, CYP4D4v2, CYP4G2, and CYP 6A38, were up-regulated in response to permethrin treatment on permethrin-resistant ALHF strains. By using PCR technology, constant overexpression of CYP 6A1, CYP 6D1 and CYP 6D3 in neocotinoid-resistant strains in Denmark during thiomethoxam challenge was demonstrated [53]. CYP6D1 was also found to be implicating more than 5000-fold of cypermethrin resistance in Learn pyrethroidresistant strain found in New York [54]. Significant increase in non-specific esterases and glutathione S-transferases activities were also evaluated [34]. A remarkable drop on GST activity has been reported on a DDT-resistant strain 698ab [27]. Point mutation was reported as the cause of insecticide sensitivity in the case of acetylcholinesterases (E.C 3.1.1.7) [55]. As far as metabolic-based resistance is concerned, there are still much more questions to be addressed. A study [31] stated that there is very little knowledge about the mechanism of the pyrethroid resistance (monooxygenase/ CYP450), although pathways have been elucidated via genomic means. There was a significant correlation between kdr allele (i.e. genes reducing the sensitivity of the nervous system to pyrethroids) frequencies and the levels of knockdown resistance by deltamethrin via a PCR-based assay [33]. It was also demonstrated that a behavioural resistance might be playing a role in contributing such resistance and such traits are still being inherited in the field [25]. The upregulation mediated by changes to transacting factors reveals that these mechanisms were underlying in some cases

**3. Impact of oxidative stress-induced resistance**

*DOI: http://dx.doi.org/10.5772/intechopen.87952*

## **3. Impact of oxidative stress-induced resistance**

*Trends in Integrated Insect Pest Management*

*Entamoeba* [16] and eggs of several tapeworms [18]. In 2010, there were further proof on transmission of Newcastle disease virus (NDV—*Paramyxoviridae*), a highly infectious virus shed in the faeces in infectious birds [19] with *Musca domestica* as vector in both field and laboratory. More recently, *Musca domestica* were also reported to carry antibiotic-resistant bacteria such as methicillin-resistant *Staphylococcus* and ticarcilin-resistant *Pseudomonas* [20], which possess threat in hospitals and healthcare facilities [18]. Flies are causing 6 million cases of childhood blindness each year (http://www.who.int/topics/trachoma/en/). *Musca domestica* also create implications in economical ways, and costs of pesticides were estimated at more than US\$200 mil-

The types of insecticides used to control houseflies on field are adulticides and larvicides (www.flycontrol.norvatis.com). Adulticides are carbamates (e.g. propoxur and methomyl), organophosphates (e.g. fenitrophon, azamethiphos and dimethoate), pyrethroids (e.g. cyfluthrin, deltamethrin and permethrin) and recently neonicotinoids (e.g. imidacloprid, thiamethoxam). Larvicides are insect growth regulators (IGRs) (e.g. triflumuron, diflubenzuron, cyromazine [23], and novaluron and juvenile hormone synthetic analogues (e.g. methoprene, fenoxycarb, pyriproxyfen [23] (www.flycontrol.novartis.com). Since the first case of DDT resistance is reported on the housefly [24], resistance of adult *Musca domestica* towards various insecticides in various sites (agricultural, wild and urban) is a fast-growing global issue. There has been an increasing resistance profile report from various places in the world.

In the United Kingdom, a resistance risk assessment done by [25] showed that although farmers claimed they had reduced using insecticides (a measure to reduce selective stress on field housefly strains), there was no sign of decrease of housefly resistance towards piperonyl butoxide synergized pyrethrins. Flies with high fenitrothion and dimethoate resistance were also discovered in Denmark [26]. In 1997, an increase in pyrethroid-resistant strains and widespread of azamethiphosresistant strains in 21 different farms all over Denmark were confirmed [27]. In Argentina, a first insecticide survey was reported [28]. Several *Musca domestica* populations were found to be permethrin-, dichlorovinyl dimethyl phosphate (an organophosphate)- and cyromazine-resistant. In the neighbouring Brazil, [29] led a first evaluation of cyromazine resistance of houseflies in five different sites, and three out of the five sites indicated cyromazine resistance. There was a report suggesting the occurrence of insecticide tolerance in tsunami-hit villages in India [30]. With hygiene at minimum provision, immediate fly control was imposed by spraying 76% dichlorvos, and LD90 of adult housefly was 3.5–3.9 times higher than the flies from control sites. As in the United States, in a study tested against nine insecticides, the fly strains showed high resistances in tetrachlorvinphos, permethrin and cyfluthrin [31], while in southeastern Nebraska, houseflies are shown to be moderately resistant to permethrin yet extremely resistant to stirofos and methoxychlor [32]. Deltamethrin-resistant flies were discovered in urban garbage

In Malaysia, [34] resistance of housefly from a garbage dump, poultry farm and agricultural farm was evaluated. It was shown that garbage dump and poultry farm fly samples were more resistant than agricultural farm. It was also shown that two poultry farms in the state of Penang against malathion, propoxur and DDT, with resistance ratio, have been found with strong correlations against relative humidity, which is a first in field discovery [35]. However, on housefly larvae, resistance assessment has been relatively scarce with only a handful of feeding and toxicity tests done. A report on an increase in diflubenzuron resistance and new-found cyromazine resistant strain was also obtained [36]. A dip test-emergence test of *Musca domestica* third instar larvae on eucalyptol extracts has been done [37] with LD50 values of 118 mg/fly and 177 mg/fly on male and female flies, respectively.

lion yearly in the United States [21] and US\$1.6 million in 1998 [22].

dump of cities of Beijing, Tianjin and Zhangjiakou [33].

**20**

In an oxidative stress-induced insecticide resistance research, rats [38–40], humans [41], fresh water fish *Brycon cephalus* [42] and black tiger shrimp *Penaeus monodon* [43] have been used as models to investigate insecticide inflicted oxidative stress. Insecticides including pyrethroids [44, 45], organophosphates [46–48] and organochlorines [49] have known to be inducing oxidative stress. It was reported that there were changes in activities of the antioxidative enzymes such as superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase and in GSH level changes both in the liver and erythrocyte homogenate [39]. Molecular resistances are consisted of target site resistance and metabolic-based resistance [50]. Yet, most of the works, as far as *Musca domestica* is concerned, have been more in top-down approach. While genome sequencing was still ongoing for that time being, specific gene family is identified and sequenced before getting into expression studies. With other fly species such as the dipteran *Drosophila melanogaster* and *Anopheles* genome as comparable reference database, it was also concluded three groups of gene superfamilies are involved in metabolic-based resistance [51], i.e. glutathione S-transferases, cytochrome P450 and acetylcholinesterase.

In cytochrome P450, [52] it was revealed that three P450 genes, CYP4D4v2, CYP4G2, and CYP 6A38, were up-regulated in response to permethrin treatment on permethrin-resistant ALHF strains. By using PCR technology, constant overexpression of CYP 6A1, CYP 6D1 and CYP 6D3 in neocotinoid-resistant strains in Denmark during thiomethoxam challenge was demonstrated [53]. CYP6D1 was also found to be implicating more than 5000-fold of cypermethrin resistance in Learn pyrethroidresistant strain found in New York [54]. Significant increase in non-specific esterases and glutathione S-transferases activities were also evaluated [34]. A remarkable drop on GST activity has been reported on a DDT-resistant strain 698ab [27]. Point mutation was reported as the cause of insecticide sensitivity in the case of acetylcholinesterases (E.C 3.1.1.7) [55]. As far as metabolic-based resistance is concerned, there are still much more questions to be addressed. A study [31] stated that there is very little knowledge about the mechanism of the pyrethroid resistance (monooxygenase/ CYP450), although pathways have been elucidated via genomic means. There was a significant correlation between kdr allele (i.e. genes reducing the sensitivity of the nervous system to pyrethroids) frequencies and the levels of knockdown resistance by deltamethrin via a PCR-based assay [33]. It was also demonstrated that a behavioural resistance might be playing a role in contributing such resistance and such traits are still being inherited in the field [25]. The upregulation mediated by changes to transacting factors reveals that these mechanisms were underlying in some cases of resistances of P450, GSTs, and acetylcholinesterases [56, 57].

## **3.1 Enzymatic removal of cellular hydrogen peroxide**

It was suggested that aerobic organisms survive due to their evolved antioxidant capability [58]. Catalase (EC 1.11.1.6) was discovered in tobacco extracts [59]. Catalase detoxifies H2O2 into water and oxygen [60]. Catalase is one of the welldescribed enzymes, and it is a class of enzyme including the iron-heme enzyme, catalase-peroxidases and a small group of manganese enzymes [61]. Superoxide dismutase (EC 1.15.1.1) is a well-known enzyme against oxidative stress. SOD1, the first superoxide dismutase to be identified, uses free radical as a substrate [62]. A metalloenzyme, superoxide dismutase catalyses the dismutation of superoxide anion (O2<sup>−</sup>) to hydrogen peroxide and oxygen, as the first defence line against oxidative stress [63]. They are also known to exhibit additional peroxidase activity when hydrogen peroxide level is at its large. It has been suggested that the removal of superoxide

anion will reduce SOD alternate toxic behaviour [6]. Copper-zinc and manganese SODs scavenge and dismutate superoxide anion in mitochondrial electron transport systems. It was demonstrated that a manganese superoxide dismutase-deficient yeast thrived in hyperoxia conditions (95% oxygen, 5% carbon dioxide) under the removal of electron transport system [64]. A copper-zinc SOD1 in baker's yeast was characterized at the intermembrane space of mitochondria [65].

Glutathione peroxidase (EC 1.11.1.9) utilizes reduced glutathione (GSH) to decompose hydrogen peroxide [66–68]. This enzyme was discovered [66] and identified as selenocysteine enzymes at first [69], better known as GPx1. Later, more selenocysteines were identified such as GPxs-GPx2, GPx3, and GPx4 [70]. It was also found in mammals [68, 71]. Later, a catalytic cysteine residue on rat was discovered [72], known as GPx5, and followed by GPx6 [73] which is a selenocysteine proteins in humans but not in rats or mice [74]. Mammalians GPx7 and GPx8 were the last to be elucidated but have a low GPx activity [75].

Peroxiredoxins (EC 1.11.1.15) are another group of enzymes worth mentioning when discussing about oxidative stress in cellular organisms. Peroxiredoxins are a family of antioxidant enzymes [76]. Highly specific in reducing hydrogen peroxide [77], its cysteine residue makes up the active site of peroxiredoxins, which in turn are being oxidized into sulfenic acid and recycled back to thiol, via sulfiredoxins [78]. They also control cytokine-induced peroxide levels which, in turn, mediate signal transduction in mammalian cells [79].

## **4. Oxidative stress-related proteins in** *Musca domestica*

There are several possible candidates of oxidative stress defence proteins. Those are superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferases, GSSG reductase, thiol transferases, gamma-glutamylcysteine synthetase, and glucose-6-phosphate dehydrogenase. Oxidative stress hypothesis is evident on aging and has always been raising questions from researchers. *Musca domestica* [80], *Drosophila melanogaster* [81, 82] and *Caenorhabditis elegans* [83] are made as model tested on hyperoxia conditions. Aging is resulted from oxidative damage from cellular macromolecules [81]. It was stated that the main prediction of this hypothesis is that the rate of aging cannot be slowed down without corresponding attenuation of oxidative damage/stress [84].

GST gene family and their isoforms have been discovered to participate in oxidative stress pathway. Overexpression and peroxidase activity of GSTs in peroxide treatment were observed [85]. Other than oxidative stress resistance, GSTs detoxify xenobiotics, protect from tissue damage, participate in Jun-kinase signaling pathway and act as non-catalytic carrier proteins (ligandins) in the intracellular transport of hydrophobic compounds [3–5]. Glutathione synthetase (GSHs) are responsible in the antioxidant defence as the dominant non-protein sulphhydryls in the cell [86] forming conjugates non-enzymatically or more by the catalysis and mediation of GSTs. H2O2 oxidizes thiolate group in cysteine residues (-S-) into thiols (-SOH), which is present in the exposing active site. Reaction against peroxidants is also energy-consuming due to the inhibition of oxidative phosphorylation [87] and deprives energy to maintain the recycling of NADPH during pentose phosphate pathway and glucose 6-phosphate dehydrogenase, making cells hyperglycaemic [88] and able to topple the condition of cell redox levels in levels of lactate/pyruvate ratio [89]. Most of the cases above were investigated towards organophosphates and pyrethroids. In cadmium ion treatment, concentration ranging from 0.2 to 5 mM in the medium, widely known to enhance reactive oxygen species in cell, increases the levels of superoxide dismutase [90]. Lowering the intake of selenium

**23**

*Defence against Oxidative Stress and Insecticides in* Musca domestica

against insecticides in *Musca domestica* is better understood.

Fundamental Research Grant (FRGS: FP052-2014A).

via diet increases the events of a peroxidative injury. The group further purified the selenium-independent glutathione peroxidase [8] and suggested this enzyme and the related pathways should be in the picture during the investigation of insect antioxidant defence system. There was no direct research work on peroxiredoxins with relation to houseflies, and its mechanisms and activities in vivo are not much of knowledge. However, it was discovered that there was no increase in catalase activity even though the diet of selenium in *Musca domestica* was lowered [7]. Another investigation [9] in houseflies revealed that the total inhibition of catalase also did not affect the survival of the flies, although slight increase in the level of

Despite such remarkable immunity and rising insecticide tolerance exhibited by *Musca domestica*, and being such prominence as model for biochemistry and insect physiology, no genome project has been launched till 2009 [2]. More importantly, to the best of our knowledge, only a handful of *Musca domestica*-related proteomic work has been reported. However, in this last 5 years, there is an increasing interest unravelling the inner molecular workings of this insect. A genome project was launched [2], and a full genome of *Musca domestica* was successfully sequenced [91]. The sequenced genome is 691 MB, and some gene sequences notably 771 putative immune-related, 86 CYP450-related, and 33 glutathione S-transferase and 92 are predicted to have esterase activities. In comparison, this genome contained a plethora of shared and novel sequences than its *Drosophila* counterparts, supporting the fact of an exemplary ability of *Musca domestica* of associating closely with numerous amounts of pathogens living in a septic environment. Pioneering transcriptomic works have been done on *Musca domestica* larvae, by massive cDNA parallel pyrosequencing [92]. Thus with the help of recent advancement, a better insight on the mechanisms that are associated with oxidative stress and resistance

The work has been funded by the University of Malaya Postgraduate Research

Fund (PPP: PV091/2011A) and Ministry of Higher Education under the

*DOI: http://dx.doi.org/10.5772/intechopen.87952*

SOD activity was observed.

**5. Conclusion**

**Acknowledgements**

#### *Defence against Oxidative Stress and Insecticides in* Musca domestica *DOI: http://dx.doi.org/10.5772/intechopen.87952*

via diet increases the events of a peroxidative injury. The group further purified the selenium-independent glutathione peroxidase [8] and suggested this enzyme and the related pathways should be in the picture during the investigation of insect antioxidant defence system. There was no direct research work on peroxiredoxins with relation to houseflies, and its mechanisms and activities in vivo are not much of knowledge. However, it was discovered that there was no increase in catalase activity even though the diet of selenium in *Musca domestica* was lowered [7]. Another investigation [9] in houseflies revealed that the total inhibition of catalase also did not affect the survival of the flies, although slight increase in the level of SOD activity was observed.

## **5. Conclusion**

*Trends in Integrated Insect Pest Management*

ized at the intermembrane space of mitochondria [65].

were the last to be elucidated but have a low GPx activity [75].

**4. Oxidative stress-related proteins in** *Musca domestica*

signal transduction in mammalian cells [79].

ing attenuation of oxidative damage/stress [84].

anion will reduce SOD alternate toxic behaviour [6]. Copper-zinc and manganese SODs scavenge and dismutate superoxide anion in mitochondrial electron transport systems. It was demonstrated that a manganese superoxide dismutase-deficient yeast thrived in hyperoxia conditions (95% oxygen, 5% carbon dioxide) under the removal of electron transport system [64]. A copper-zinc SOD1 in baker's yeast was character-

Glutathione peroxidase (EC 1.11.1.9) utilizes reduced glutathione (GSH) to decompose hydrogen peroxide [66–68]. This enzyme was discovered [66] and identified as selenocysteine enzymes at first [69], better known as GPx1. Later, more selenocysteines were identified such as GPxs-GPx2, GPx3, and GPx4 [70]. It was also found in mammals [68, 71]. Later, a catalytic cysteine residue on rat was discovered [72], known as GPx5, and followed by GPx6 [73] which is a selenocysteine proteins in humans but not in rats or mice [74]. Mammalians GPx7 and GPx8

Peroxiredoxins (EC 1.11.1.15) are another group of enzymes worth mentioning when discussing about oxidative stress in cellular organisms. Peroxiredoxins are a family of antioxidant enzymes [76]. Highly specific in reducing hydrogen peroxide [77], its cysteine residue makes up the active site of peroxiredoxins, which in turn are being oxidized into sulfenic acid and recycled back to thiol, via sulfiredoxins [78]. They also control cytokine-induced peroxide levels which, in turn, mediate

There are several possible candidates of oxidative stress defence proteins. Those are superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferases, GSSG reductase, thiol transferases, gamma-glutamylcysteine synthetase, and glucose-6-phosphate dehydrogenase. Oxidative stress hypothesis is evident on aging and has always been raising questions from researchers. *Musca domestica* [80], *Drosophila melanogaster* [81, 82] and *Caenorhabditis elegans* [83] are made as model tested on hyperoxia conditions. Aging is resulted from oxidative damage from cellular macromolecules [81]. It was stated that the main prediction of this hypothesis is that the rate of aging cannot be slowed down without correspond-

GST gene family and their isoforms have been discovered to participate in oxidative stress pathway. Overexpression and peroxidase activity of GSTs in

peroxide treatment were observed [85]. Other than oxidative stress resistance, GSTs detoxify xenobiotics, protect from tissue damage, participate in Jun-kinase signaling pathway and act as non-catalytic carrier proteins (ligandins) in the intracellular transport of hydrophobic compounds [3–5]. Glutathione synthetase (GSHs) are responsible in the antioxidant defence as the dominant non-protein sulphhydryls in the cell [86] forming conjugates non-enzymatically or more by the catalysis and mediation of GSTs. H2O2 oxidizes thiolate group in cysteine residues (-S-) into thiols (-SOH), which is present in the exposing active site. Reaction against peroxidants is also energy-consuming due to the inhibition of oxidative phosphorylation [87] and deprives energy to maintain the recycling of NADPH during pentose phosphate pathway and glucose 6-phosphate dehydrogenase, making cells hyperglycaemic [88] and able to topple the condition of cell redox levels in levels of lactate/pyruvate ratio [89]. Most of the cases above were investigated towards organophosphates and pyrethroids. In cadmium ion treatment, concentration ranging from 0.2 to 5 mM in the medium, widely known to enhance reactive oxygen species in cell, increases the levels of superoxide dismutase [90]. Lowering the intake of selenium

**22**

Despite such remarkable immunity and rising insecticide tolerance exhibited by *Musca domestica*, and being such prominence as model for biochemistry and insect physiology, no genome project has been launched till 2009 [2]. More importantly, to the best of our knowledge, only a handful of *Musca domestica*-related proteomic work has been reported. However, in this last 5 years, there is an increasing interest unravelling the inner molecular workings of this insect. A genome project was launched [2], and a full genome of *Musca domestica* was successfully sequenced [91]. The sequenced genome is 691 MB, and some gene sequences notably 771 putative immune-related, 86 CYP450-related, and 33 glutathione S-transferase and 92 are predicted to have esterase activities. In comparison, this genome contained a plethora of shared and novel sequences than its *Drosophila* counterparts, supporting the fact of an exemplary ability of *Musca domestica* of associating closely with numerous amounts of pathogens living in a septic environment. Pioneering transcriptomic works have been done on *Musca domestica* larvae, by massive cDNA parallel pyrosequencing [92]. Thus with the help of recent advancement, a better insight on the mechanisms that are associated with oxidative stress and resistance against insecticides in *Musca domestica* is better understood.

## **Acknowledgements**

The work has been funded by the University of Malaya Postgraduate Research Fund (PPP: PV091/2011A) and Ministry of Higher Education under the Fundamental Research Grant (FRGS: FP052-2014A).

*Trends in Integrated Insect Pest Management*

## **Author details**

Tan Yong Hao1 , Siti Nasuha Hamzah<sup>2</sup> and Zazali Alias1,3\*

1 Faculty of Science, Institute of Biological Sciences, University of Malaya, Kuala Lumpur, Malaysia

2 School of Biological Sciences, Universiti Sains Malaysia, Pulau Pinang, Malaysia

3 University of Malaya Halal Research Centre (UMHRC), University of Malaya, Kuala Lumpur, Malaysia

\*Address all correspondence to: alias@um.edu.my

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**25**

*Defence against Oxidative Stress and Insecticides in* Musca domestica

*Part B: Comparative Biochemistry*.

[9] Allen RG, Farmer KJ, Sohal RS. Effect of catalase inactivation on levels of inorganic peroxides, superoxide dismutase, glutathione, oxygen consumption and life span in adult houseflies (*Musca domestica*). Biochemical Journal.

[10] Dahlem G. House fly (*Musca domestica*). In: Resh V, Carde R, editors. Encyclopedia on Insects. 1st ed. Vol. 1. San Diego: CA Academic Press; 2003.

[11] Marshall S. Insects: Their Natural History and Diversity. Buffalo, New York: Firefly Books Ltd; 2006

[12] Greenberg B, Kowalski JA, Klowden MJ. Factors affecting the transmission

resistance to colonization and bacterial interference. Infection and Immunity.

[13] Kettle DS. Muscidae (houseflies, stableflies). In: Kettle DS, editor. Medical and Veterinary Entomology. Wallingford: CAB International; 1990.

[14] Grubel P, Hoffman JS, Chong FK, Burstein NA, Mepani C, Cave D. Vector potential of houseflies (Musca domestica) for Helicobacter pylori. Journal of Clinical Microbiology.

[15] Zurek L, Denning SS, Schal C, Watson DW. Vector competence of *Musca domestica* (Diptera: Muscidae) for *Yersinia pseudotuberculosis*. Journal of Medical Entomology. 2001;**38**:333-335

[16] Ugbogu OC, Nwachukwu NC, Ogbuagu MN. Isolation of *Salmonella* and *Shigella* species from houseflies

of salmonella by flies: Natural

1989;**94**(2):323-332

1983;**216**(2):503-506

pp. 532-534

1970;**2**:800-809

pp. 223-240

1997;**35**:1300-1303

*DOI: http://dx.doi.org/10.5772/intechopen.87952*

[1] Thompson FC. Biosystematic Database of World Diptera. 2004. Retrieved from: www.diptera.org Trachoma. (n.d.). In: World Health Organization's website. Retrieved from: http://www.who.int/topics/

[2] Scott JG, Liu N, Kristensen M, Clark AG. A case for sequencing the genome of *Musca domestica* (Diptera: Muscidae). Journal of Medical Entomology. 2009;**46**(2):175-182

S-transferases and prevention of cellular free radical damage. Free Radical Research. 1998;**28**:647-668

[4] Strange RC, Jones PW, Fryer AA. Glutathione S-transferase: Genetics and role in toxicology. Toxicology Letters.

[5] Yin Z, Ivanov VN, Habelhah H, Tew K, Ronai Z. Glutathione S-transferase elicits protection against H2O2-induced cell death via coordinated regulation of stress kinases. Cancer Research.

[6] den Hartog GJM, Haenen GRMM, Vegt E, van der Vijgh WJF, Bast A. Superoxide dismutase: The balance between prevention and induction of oxidative damage. Chemico-Biological

[7] Simmons TW, Jamail IS, Lockshin RA. The effect of selenium deficiency on peroxidative injury in the house fly, Musca domestica: A role for glutathione peroxidase. FEBS Letters.

[8] Simmons TW, Jamail IS, Lockshin RA. Selenium-independent glutathione peroxidase activity associated with glutathione S-transferase from the housefly. *Musca domestica.* 

*Comparative Biochemistry and Physiology* 

Interactions. 2003;**145**:33-39

1987;**218**(2):251-254

[3] Ketterer B. Glutathione

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*Defence against Oxidative Stress and Insecticides in* Musca domestica *DOI: http://dx.doi.org/10.5772/intechopen.87952*

## **References**

*Trends in Integrated Insect Pest Management*

**24**

**Author details**

Kuala Lumpur, Malaysia

Kuala Lumpur, Malaysia

, Siti Nasuha Hamzah<sup>2</sup>

\*Address all correspondence to: alias@um.edu.my

provided the original work is properly cited.

and Zazali Alias1,3\*

1 Faculty of Science, Institute of Biological Sciences, University of Malaya,

2 School of Biological Sciences, Universiti Sains Malaysia, Pulau Pinang, Malaysia

3 University of Malaya Halal Research Centre (UMHRC), University of Malaya,

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

Tan Yong Hao1

[1] Thompson FC. Biosystematic Database of World Diptera. 2004. Retrieved from: www.diptera.org Trachoma. (n.d.). In: World Health Organization's website. Retrieved from: http://www.who.int/topics/ trachoma/en/

[2] Scott JG, Liu N, Kristensen M, Clark AG. A case for sequencing the genome of *Musca domestica* (Diptera: Muscidae). Journal of Medical Entomology. 2009;**46**(2):175-182

[3] Ketterer B. Glutathione S-transferases and prevention of cellular free radical damage. Free Radical Research. 1998;**28**:647-668

[4] Strange RC, Jones PW, Fryer AA. Glutathione S-transferase: Genetics and role in toxicology. Toxicology Letters. 2000;**15**:357-363

[5] Yin Z, Ivanov VN, Habelhah H, Tew K, Ronai Z. Glutathione S-transferase elicits protection against H2O2-induced cell death via coordinated regulation of stress kinases. Cancer Research. 2000;**60**:4053-4057

[6] den Hartog GJM, Haenen GRMM, Vegt E, van der Vijgh WJF, Bast A. Superoxide dismutase: The balance between prevention and induction of oxidative damage. Chemico-Biological Interactions. 2003;**145**:33-39

[7] Simmons TW, Jamail IS, Lockshin RA. The effect of selenium deficiency on peroxidative injury in the house fly, Musca domestica: A role for glutathione peroxidase. FEBS Letters. 1987;**218**(2):251-254

[8] Simmons TW, Jamail IS, Lockshin RA. Selenium-independent glutathione peroxidase activity associated with glutathione S-transferase from the housefly. *Musca domestica. Comparative Biochemistry and Physiology*  *Part B: Comparative Biochemistry*. 1989;**94**(2):323-332

[9] Allen RG, Farmer KJ, Sohal RS. Effect of catalase inactivation on levels of inorganic peroxides, superoxide dismutase, glutathione, oxygen consumption and life span in adult houseflies (*Musca domestica*). Biochemical Journal. 1983;**216**(2):503-506

[10] Dahlem G. House fly (*Musca domestica*). In: Resh V, Carde R, editors. Encyclopedia on Insects. 1st ed. Vol. 1. San Diego: CA Academic Press; 2003. pp. 532-534

[11] Marshall S. Insects: Their Natural History and Diversity. Buffalo, New York: Firefly Books Ltd; 2006

[12] Greenberg B, Kowalski JA, Klowden MJ. Factors affecting the transmission of salmonella by flies: Natural resistance to colonization and bacterial interference. Infection and Immunity. 1970;**2**:800-809

[13] Kettle DS. Muscidae (houseflies, stableflies). In: Kettle DS, editor. Medical and Veterinary Entomology. Wallingford: CAB International; 1990. pp. 223-240

[14] Grubel P, Hoffman JS, Chong FK, Burstein NA, Mepani C, Cave D. Vector potential of houseflies (Musca domestica) for Helicobacter pylori. Journal of Clinical Microbiology. 1997;**35**:1300-1303

[15] Zurek L, Denning SS, Schal C, Watson DW. Vector competence of *Musca domestica* (Diptera: Muscidae) for *Yersinia pseudotuberculosis*. Journal of Medical Entomology. 2001;**38**:333-335

[16] Ugbogu OC, Nwachukwu NC, Ogbuagu MN. Isolation of *Salmonella* and *Shigella* species from houseflies

(*Musca domestica* L.) in Utru, Nigeria. The African Journal of Biotechnology. 2006;**5**:1090-1091

[17] Szalanski AL, Owens CB, Mckay T, Steelman CD. Detection of *Campylobacter* and *Escherichia coli* O157:H7 from filth flies by polymerase chain reaction. Medical and Veterinary Entomology. 2004;**18**:241-246

[18] Graczyk TK, Knight R, Gilman RH, Cranfield MR. The role of non biting flies in the epidemiology of human infectious diseases. Microbes and Infection. 2001;**3**:231-235

[19] Barin A, Arabkhazaeli F, Rahbari S, Madani SA. The housefly, *Musca domestica*, as a possible mechanical vector of Newcastle disease virus in the laboratory and field. Medical and Veterinary Entomology. 2010;**24**:88-90

[20] Boulesteix G, Le Dantec P, Chevalier B, Dieng M, Niang B, Diatta B. Role of Musca domestica in the transmission of multiresistant bacteria in the centres of intensive care setting in a sub-Saharan Africa. Annales Francaises d'Anesthésie et de Réanimation. 2005;**24**:361-365

[21] Geden CJ, Arends JJ, Axtell RC, Barnard DR, Gaydon DM, Hickle LA, Hogstette JA, Jones WF, Mullens BA, Nolan Jr. MP, Petersen JJ, and Sheppard DC. Economic significance of poultry. In: Geden CJ, and Hogsette JA, editors, Research and extension needs for integrated pest management for arthropods of veterinary importance: Proceedings of a Workshop in Lincoln; 12-14 April 1994; Nebraska Gainesville, Florida: Center for Medical, Agricultural, and Veterinary Entomology USDA-ARS; pp. 1-328

[22] Crespo DC, Lecuona RE, Hogsette JA. Biological control: An important component in integrated management of *Musca domestica* (Diptera: Muscidae) in caged layer poultry houses in Buenos Aires. Biological Control. 1998;**13**:16-24

[23] Kočišová A, Petrovský M, Toporčák J, Novák P. The potential of some insect growth regulators in housefly (*Musca domestica*) control. Biologia. 2004;**59**:661-668

[24] Saccà GS. Estenza di *mosche domestiche* resistenti al DDT. Rivista di Parassitologia. 1947;**8**:127-128

[25] Learmount J, Chapman P, Macnicoll A. Impact of an insecticide resistance strategy for house fly (Diptera: Muscidae) control in intensive animal units in the United Kingdom. Journal of Economic Entomology. 2002;**95**(6):1245-1250

[26] Keiding J. The House Fly—Biology and Control. Geneva: World Health Organization; 1986

[27] Kristensen M. Glutathione S-transferase and insecticide resistance in laboratory strains and field populations of *Musca domestica*. Journal of Economic Entomology. 2005;**98**(4):1341-1348

[28] Acevedo GR, Zapater M, Toloza AC. Insecticide resistance of house fly, *Musca domestica* (L.) from Argentina. Parasitology Research. 2009;**105**:489-493

[29] Pinto MC, Prado APD. Resistance of *Musca domestica* L. populations to cyromazine (insect growth regulator) in Brazil. Memórias do Instituto Oswaldo Cruz. 2001;**96**(5):729-732

[30] Srinivasan R, Jambulingam P, Gunasekaran K, Boopathidoss P. Tolerance of housefly, *Musca domestica* L. (Diptera: Muscidae) to dichlorvos (76% EC) an insecticide used for fly control in the tsunami-hit coastal villages of southern India. Acta Tropica. 2008;**105**:187-190

[31] Scott JG, Alefantis TG, Kaufman PE, Rutz DA. Insecticide resistance in house flies from caged-layer poultry

**27**

*Defence against Oxidative Stress and Insecticides in* Musca domestica

intoxicated with chlorfenvinphos in low doses. Polish Journal of Environmental

Studies. 1999;**8**:234-236

2003;**12**:417-423

[39] Lukaszewicz-Hussain A, Moniuszko-Jakoniuk J. Organophosphate insecticide chlorfenvinphos affects enzymatic and nonenzymatic antioxidants in erythrocytes and serum of rats. Polish Journal of Environmental Studies.

[40] El-Demerdash FM. Lipid peroxidation, oxidative stress and acetylcholinesterase in rat brain exposed to organophosphate and pyrethroid insecticides. Food and Chemical Toxicology. 2011;**49**:1346-1352

[41] Ranjbar A, Solhi H, Mashayekhi FJ, Susanabdi A, Rezaie A, Abdollahi M. Oxidative stress in acute human poisoning with organophosphorus insecticides; a case control study. Environmental Toxicology and Pharmacology. 2005;**20**:88-91

[42] Monteiro DA, Rantin FT, Kalinin AL. The effects of selenium on oxidative stress biomarkers in the freshwater characid fish matrinxã, *Brycon cephalus* (Günther, 1869)

exposed to organophosphate insecticide Folisuper 600 BR® (methyl parathion).

Comparative Biochemistry and Physiology (Part C). 2009;**149**:40-49

[43] Dorts J, Silvestrea F, Huynh TT, Tybergheina AE, Nguyen TP, Kestemonta P. Oxidative stress, protein carbonylation and heat shock proteins in the black tiger shrimp, Penaeus monodon, following exposure to endosulfan and deltamethrin. Environmental Toxicology and Pharmacology. 2009;**28**:302-310

[44] Giray B, Gürbay A, Hincal F. Cypermethrin-induced oxidative stress in rat brain and liver is prevented by vitamin E or allopurinol. Toxicology

Letters. 2001;**118**:139-146

*DOI: http://dx.doi.org/10.5772/intechopen.87952*

(Diptera: Muscidae) from Southeastern Nebraska beef cattle feedlots to selected insecticides. Journal of Economic Entomology. 2003;**96**(3):1016-1020

facilities. Pest Management Science.

[32] Marçon PCRG, Thomas GD, Siegfried BD, Campbell JB, Skoda SR. Resistance status of house flies

[33] Cao XM, Song FL, Zhao TY, Dong YD, Sun CHX, Lui BL. Survey of deltamethrin resistance in house flies (*Musca domestica*) from urban garbage dumps in northern China. Environmental Entomology.

[34] Nazni WA, Ursula MP, Lee HL, Sa'diyah I. Susceptibility of Musca domestica L. (Diptera: Muscidae) from various breeding sites to commonly used insecticides. Journal of Vector

Ecology. 1999;**24**(1):54-60

[35] Bong LJ, Zairi J. Temporal

[36] Kristensen M, Jespersen JB. Larvicide resistance in *Musca domestica* (Diptera: Muscidae) populations in Denmark and

strains. Journal of Economic Entomology. 2003;**96**(4):1300-1306

2004;**46**(2):97-101

[37] Sukontason KL, Boonchu N, Sukontason K, Choochote W. Effects of eucalyptol on housefly (Diptera: Muscidae) and blow fly (Diptera: Calliphoridae). Revista do Instituto de Medicina Tropical de São Paulo.

[38] Lukaszewicz-Hussain A, Moniuszko-Jakoniuk J. Activities of superoxide dismutase and catalase in erythrocytes and concentration of malondialdehyde in serum of rats

fluctuations of insecticides resistance in *Musca domestica* Linn. (Diptera: Muscidae) in Malaysia. Tropical Biomedicine. 2010;**27**(2):317-325

establishment of resistant laboratory

2000;**56**:147-153

2006;**35**(1):1-9

*Defence against Oxidative Stress and Insecticides in* Musca domestica *DOI: http://dx.doi.org/10.5772/intechopen.87952*

facilities. Pest Management Science. 2000;**56**:147-153

*Trends in Integrated Insect Pest Management*

(*Musca domestica* L.) in Utru, Nigeria. The African Journal of Biotechnology. [23] Kočišová A, Petrovský M, Toporčák J, Novák P. The potential of some insect growth regulators in housefly (*Musca domestica*) control. Biologia.

[25] Learmount J, Chapman P, Macnicoll A. Impact of an insecticide resistance strategy for house fly (Diptera: Muscidae) control in intensive animal units in the United Kingdom. Journal of Economic Entomology.

[26] Keiding J. The House Fly—Biology and Control. Geneva: World Health

[27] Kristensen M. Glutathione S-transferase and insecticide resistance in laboratory strains and field populations of *Musca domestica*. Journal of Economic Entomology.

[28] Acevedo GR, Zapater M, Toloza AC. Insecticide resistance of house fly, *Musca domestica* (L.) from Argentina. Parasitology Research.

[29] Pinto MC, Prado APD. Resistance of *Musca domestica* L. populations to cyromazine (insect growth regulator) in Brazil. Memórias do Instituto Oswaldo

[24] Saccà GS. Estenza di *mosche domestiche* resistenti al DDT. Rivista di

Parassitologia. 1947;**8**:127-128

2002;**95**(6):1245-1250

Organization; 1986

2005;**98**(4):1341-1348

2009;**105**:489-493

2008;**105**:187-190

Cruz. 2001;**96**(5):729-732

[30] Srinivasan R, Jambulingam P, Gunasekaran K, Boopathidoss P. Tolerance of housefly, *Musca domestica* L. (Diptera: Muscidae) to dichlorvos (76% EC) an insecticide used for fly control in the tsunami-hit coastal villages of southern India. Acta Tropica.

[31] Scott JG, Alefantis TG, Kaufman PE, Rutz DA. Insecticide resistance in house flies from caged-layer poultry

2004;**59**:661-668

[17] Szalanski AL, Owens CB, Mckay T, Steelman CD. Detection of *Campylobacter* and *Escherichia coli* O157:H7 from filth flies by polymerase chain reaction. Medical and Veterinary

Entomology. 2004;**18**:241-246

Infection. 2001;**3**:231-235

[18] Graczyk TK, Knight R, Gilman RH, Cranfield MR. The role of non biting flies in the epidemiology of human infectious diseases. Microbes and

[19] Barin A, Arabkhazaeli F, Rahbari S, Madani SA. The housefly, *Musca domestica*, as a possible mechanical vector of Newcastle disease virus in the laboratory and field. Medical and Veterinary Entomology. 2010;**24**:88-90

[20] Boulesteix G, Le Dantec P, Chevalier B, Dieng M, Niang B, Diatta B. Role of Musca domestica in the transmission of multiresistant bacteria in the centres of intensive care setting in a sub-Saharan Africa. Annales Francaises d'Anesthésie et de Réanimation. 2005;**24**:361-365

[21] Geden CJ, Arends JJ, Axtell RC, Barnard DR, Gaydon DM, Hickle LA, Hogstette JA, Jones WF, Mullens BA, Nolan Jr. MP, Petersen JJ, and Sheppard DC. Economic significance of poultry. In: Geden CJ, and Hogsette JA, editors, Research and extension needs for integrated pest management for arthropods of veterinary importance:

Proceedings of a Workshop in Lincoln; 12-14 April 1994; Nebraska Gainesville, Florida: Center for Medical, Agricultural, and Veterinary Entomology USDA-ARS; pp. 1-328

[22] Crespo DC, Lecuona RE, Hogsette JA. Biological control: An important component in integrated management of *Musca domestica* (Diptera: Muscidae) in caged layer poultry houses in Buenos Aires. Biological Control. 1998;**13**:16-24

2006;**5**:1090-1091

**26**

[32] Marçon PCRG, Thomas GD, Siegfried BD, Campbell JB, Skoda SR. Resistance status of house flies (Diptera: Muscidae) from Southeastern Nebraska beef cattle feedlots to selected insecticides. Journal of Economic Entomology. 2003;**96**(3):1016-1020

[33] Cao XM, Song FL, Zhao TY, Dong YD, Sun CHX, Lui BL. Survey of deltamethrin resistance in house flies (*Musca domestica*) from urban garbage dumps in northern China. Environmental Entomology. 2006;**35**(1):1-9

[34] Nazni WA, Ursula MP, Lee HL, Sa'diyah I. Susceptibility of Musca domestica L. (Diptera: Muscidae) from various breeding sites to commonly used insecticides. Journal of Vector Ecology. 1999;**24**(1):54-60

[35] Bong LJ, Zairi J. Temporal fluctuations of insecticides resistance in *Musca domestica* Linn. (Diptera: Muscidae) in Malaysia. Tropical Biomedicine. 2010;**27**(2):317-325

[36] Kristensen M, Jespersen JB. Larvicide resistance in *Musca domestica* (Diptera: Muscidae) populations in Denmark and establishment of resistant laboratory strains. Journal of Economic Entomology. 2003;**96**(4):1300-1306

[37] Sukontason KL, Boonchu N, Sukontason K, Choochote W. Effects of eucalyptol on housefly (Diptera: Muscidae) and blow fly (Diptera: Calliphoridae). Revista do Instituto de Medicina Tropical de São Paulo. 2004;**46**(2):97-101

[38] Lukaszewicz-Hussain A, Moniuszko-Jakoniuk J. Activities of superoxide dismutase and catalase in erythrocytes and concentration of malondialdehyde in serum of rats intoxicated with chlorfenvinphos in low doses. Polish Journal of Environmental Studies. 1999;**8**:234-236

[39] Lukaszewicz-Hussain A, Moniuszko-Jakoniuk J. Organophosphate insecticide chlorfenvinphos affects enzymatic and nonenzymatic antioxidants in erythrocytes and serum of rats. Polish Journal of Environmental Studies. 2003;**12**:417-423

[40] El-Demerdash FM. Lipid peroxidation, oxidative stress and acetylcholinesterase in rat brain exposed to organophosphate and pyrethroid insecticides. Food and Chemical Toxicology. 2011;**49**:1346-1352

[41] Ranjbar A, Solhi H, Mashayekhi FJ, Susanabdi A, Rezaie A, Abdollahi M. Oxidative stress in acute human poisoning with organophosphorus insecticides; a case control study. Environmental Toxicology and Pharmacology. 2005;**20**:88-91

[42] Monteiro DA, Rantin FT, Kalinin AL. The effects of selenium on oxidative stress biomarkers in the freshwater characid fish matrinxã, *Brycon cephalus* (Günther, 1869) exposed to organophosphate insecticide Folisuper 600 BR® (methyl parathion). Comparative Biochemistry and Physiology (Part C). 2009;**149**:40-49

[43] Dorts J, Silvestrea F, Huynh TT, Tybergheina AE, Nguyen TP, Kestemonta P. Oxidative stress, protein carbonylation and heat shock proteins in the black tiger shrimp, Penaeus monodon, following exposure to endosulfan and deltamethrin. Environmental Toxicology and Pharmacology. 2009;**28**:302-310

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*DOI: http://dx.doi.org/10.5772/intechopen.87952*

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I. Superoxide dismutase: An enzymic function for erythrocuprein. The

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O. Biochemical evidence for free radical-induced lipid peroxidation as a mechanism for subchronic toxicity of malathion in blood and liver of rats. Human and Experimental Toxicology.

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Kebryaeezadeh A, Hosseini R, Sabzevari

1999;**19**:67-72

2003;**22**:205-211

2006;**9**(1):23-28

2010;**98**(2):145-150

**28**

[63] Fridovich I. Superoxide radical and superoxide dismutases. Annual Review of Biochemistry. 1995;**64**:97-112

[64] Guidot DM, McCord JM, Wright RM, Repine JE. Absence of electron transport (Rho 0 state) restores growth of a manganesesuperoxide dismutase-deficient Saccharomyces cerevisiae in hyperoxia. Evidence for electron transport as a major source of superoxide generation in vivo. The Journal of Biological Chemistry. 1993;**268**:26699-26703

[65] Sturtz LA, Diekert K, Jensen LT, Lill R, Culotta VC. A fraction of yeast Cu, Zn-superoxide dismutase and its metallochaperone, CCS, localize to the intermembrane space of mitochondria: A physiological role for SOD1 in guarding against mitochondrial oxidative damage. The Journal of Biological Chemistry. 2001;**276**:38084-38089

[66] Mills GC. Hemoglobin catabolism. Glutathione peroxidase, an erythrocyte enzyme which protects hemoglobin from oxidative breakdown. The Journal of Biological Chemistry. 1957;**266**:20752-20760

[67] Forstrom JW, Zakowski JJ, Tappel AL. Identification of the catalytic site of rat liver glutathione peroxidase as selenocysteine. Biochemistry. 1978;**17**(13):2639-2644

[68] Ursini F, Maiorino M, Gregolin C. The selenoenzyme phospholipid hydroperoxide glutathione peroxidase. Biochimica et Biophysica Acta. 1985;**839**:62-70

[69] Chance B, Sies H, Boveris A. Hydroperoxide metabolism in mammalian organs. Physiological Reviews. 1979;**59**:527-605

[70] Chu FF, Doroshow JH, Esworthy RS. Expression characterization, and tissue-distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI. The Journal of Biological Chemistry. 1993;**268**:2571-2576

[71] Takahashi K, Avissar N, Whitin J, Cohen H. Purification and characterization of human plasma glutathione peroxidase: A selenoglycoprotein distinct from the known cellular enzyme. Archives of Biochemistry and Biophysics. 1987;**256**:677-686

[72] Ghyselinck NB, Dufaure JP. A mouse cDNA sequence for epididymal androgen regulated proteins related to glutathione peroxidase. Nucleic Acids Research. 1990;**18**:7144

[73] Dear TN, Campbell K, Rabbitts TH. Molecular cloning of putative odorant-binding and odorant metabolizing proteins. Biochemistry. 1991;**30**:10376-10382

[74] Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, Guigó R, et al. Characterization of mammalian selenoproteomes. Science. 2003;**300**:1439-1443

[75] Brigelius-Flohe R, Maiorino M. Glutathione peroxidases. Biochimica et Biophysica Acta. 1830;**2012**:3289-3303

[76] Kim K, Kim IH, Lee KY, Rhee SG, Stadtman ER. The isolation and purification of a specific "protector" protein which inhibits enzyme inactivation by a thiol/Fe(III)/O2 mixed-function oxidation system. The Journal of Biological Chemistry. 1988;**263**:4704-4711

[77] Peskin AV, Low FM, Paton LN, Maghzal GJ, Hampton MB, Winterbourn CC. The high reactivity of peroxiredoxin 2 with H2O2 is not

reflected in its reaction with other oxidants and thiol reagents. The Journal of Biological Chemistry. 2007;**282**(16):11885-11892

[78] Woo HA, Jeong W, Chang TS, Park KJ, Park SJ, Yang JS, et al. Reduction of cysteine sulfinic acid by sulfiredoxin is specific to 2-cys peroxiredoxins. The Journal of Biological Chemistry. 2005;**280**:3125-3128

[79] Hofmann B, Hecht HJ, Flohé L. Peroxiredoxins. Biological Chemistry. 2002;**383**(3-4):347

[80] Yan LJ, Levine RL, Sohal R. Effects of aging and hyperoxia on oxidative damage to cytochrome c in the housefly, *Musca domestica*. Free Radical Biology and Medicine. 2000;**29**(1):90-97

[81] Magwere T, West M, Riyahi K, Murphy MP, Smith RAJ, Partridge L. The effects of exogenous antioxidants on lifespan and oxidative stress resistance in *Drosophila melanogaster*. Mechanisms of Ageing and Development. 2005;**127**:356-370

[82] Rebrin I, Sohal R. Comparison between the effects of aging and hyperoxia on glutathione redox state and protein mixed disulfides in *Drosophila melanogaster*. Mechanisms of Ageing and Development. 2006;**127**:869-874

[83] Leiers B, Kampkötter A, Grevelding CG, Link CD, Johnson TE, Henkle Dührsen K. A stressresponsive glutathione S-transferase confers resistance to oxidative stress in Caenorhabditis elegans. Free Radical Biology and Medicine. 2003;**34**(11):1405-1415

[84] Sohal RS, Weindruch R. Oxidative stress, caloric restriction, and aging. Science. 1996;**273**:59-63

[85] Veal EA, Toone WM, Jones N, Morgan BA. Distinct roles

for glutathione S-transferases in the oxidative stress response in *Schizosaccharomyces pombe*. The Journal of Biological Chemistry. 2002;**277**(38):35523-35531

[86] Ketterer B. The role of nonenzymatic reactions of glutathione in xenobiotic mechanism. Drug Metabolism Reviews. 1982;**13**:161-187

**Chapter 3**

**Abstract**

moths [4, 5].

**31**

*Muhammad Imran*

Neonicotinoid Insecticides:

Pollination is the fundamental requirement for healthier fruit set. More than 90% of flowering plant species in the hot and humid regions required pollination. Many plants species required animal pollination. Among these animals, insects play a vital role in pollination, and among the major insect pollinators, hymenopterans, honeybees, and bumblebees are regarded as the best pollinators of the crops around the world. Declining population of these important pollinators day by day is a major threat, and this declining is due to a variety of stressors. Among these possible reasons including environmental conditions, parasites, predators, malnutrition, and diseases, many researchers pointed finger at pesticides as playing a major role especially neonicotinoid. Neonicotinoids move in the environment and can be found throughout the areas where they are not applied. Neonicotinoids can drift offsite directly exposing bees and contaminate nontargeted areas when applied as spray. During plant uptake, neonicotinoid spreads through plant tissues and disrupts the physiology of pollen eaters, nectar feeders, and the insects that feed upon plant tissues. Therefore, the use of neonicotinoid is the major reason for the decline of bees in the world. So it is requested to all farmers and researchers to

**Keywords:** pollinators, honeybees, bumblebees, insecticides, Neonicotinoid

Consideration on sustainable growth generally agrees that environment still harbors much kind of living things that are potentially and unswervingly significant to mankind. Their lucrative utilize is now pending for the discovery of their worth or the formulation of how they should be propagated. There are about 25,000 species of bees [1] recognized in the world and only few play an important role in pollination producing fruits and seeds. Most of the world wide plant species depend upon animal pollination for their fertilization [2]. Among animal pollinators (any animal which transfer pollen between plants enabling fertilization and sexual reproduction from anther of male flower part to the stigma of female flower) insects provide better service of pollination [3]. Insect pollinators include bees (honey bees, bumblebees and solitary bees), flies (Carrion flies, flesh flies and hover flies), pollen wasp, ants, mosquitoes, beetles, butterflies and

Among these major insect pollinators; hymenopterans, honey bees and bumblebees are regarded as the best pollinators of the crops around the world. It has been

A Threat to Pollinators

please find ways to kill pests not pollinators.

**1. Economic importance of pollinators**

[87] Milatovic D, Gupta RC, Aschner M. Anticholinesterase toxicity, oxidative stress. The Scientific World Journal. 2006;**6**:295-310

[88] Rahimi R, Abdollahi M. A review on the mechanisms involved in hyperglycemia induced by organophosphorus pesticides. Pesticide Biochemistry and Physiology. 2007;**88**:115-121

[89] Lukaszewicz-Hussain A, Moniuszko-Jakoniuk J. Procesy glikolityczne w wa˛trobie szczurawzatruciu chlorfenwinfosem. Medycyna Pracy. 1997;**48**:580-583

[90] Dabas A, Nagpure NS, Kumar R, Kushwaha B, Kumar P, Lakra WS. Assessment of tissue-specific effect of cadmium on antioxidant defense system and lipid peroxidation in freshwater murrel, Channa punctatus. Fish Physiology and Biochemistry. 2012;**38**(2):469-482

[91] Scott JG, Warren WC, Beukeborn LW, Bopp D, Clark AG, Giers SD, et al. Genome of the house fly, *Musca domestica* L., a global vector of diseases with adaptations to a septic environment. Genome Biology. 2014;**15**:466

[92] Liu F, Tang T, Sun L, Priya TAJ. Transcriptomic analysis of the housefly (*Musca domestica*) larva using massively parallel pyrosequencing. Molecular Biology Reports. 2012;**39**:1927-1934

## **Chapter 3**

*Trends in Integrated Insect Pest Management*

reflected in its reaction with other oxidants and thiol reagents. The Journal of Biological Chemistry. 2007;**282**(16):11885-11892

for glutathione S-transferases in the oxidative stress response in *Schizosaccharomyces pombe*. The Journal of Biological Chemistry. 2002;**277**(38):35523-35531

[86] Ketterer B. The role of

2006;**6**:295-310

2007;**88**:115-121

2012;**38**(2):469-482

2014;**15**:466

nonenzymatic reactions of glutathione in xenobiotic mechanism. Drug Metabolism Reviews. 1982;**13**:161-187

[87] Milatovic D, Gupta RC, Aschner M. Anticholinesterase toxicity, oxidative stress. The Scientific World Journal.

Pesticide Biochemistry and Physiology.

szczurawzatruciu chlorfenwinfosem. Medycyna Pracy. 1997;**48**:580-583

[90] Dabas A, Nagpure NS, Kumar R, Kushwaha B, Kumar P, Lakra WS. Assessment of tissue-specific effect of cadmium on antioxidant defense system and lipid peroxidation in freshwater murrel, Channa punctatus. Fish Physiology and Biochemistry.

[91] Scott JG, Warren WC, Beukeborn LW, Bopp D, Clark AG, Giers SD, et al. Genome of the house fly, *Musca domestica* L., a global vector of diseases with adaptations to a septic environment. Genome Biology.

[92] Liu F, Tang T, Sun L, Priya TAJ. Transcriptomic analysis of the housefly (*Musca domestica*) larva using massively parallel pyrosequencing.

Molecular Biology Reports.

2012;**39**:1927-1934

[88] Rahimi R, Abdollahi M. A review on the mechanisms involved in hyperglycemia induced by organophosphorus pesticides.

[89] Lukaszewicz-Hussain A, Moniuszko-Jakoniuk J. Procesy glikolityczne w wa˛trobie

[78] Woo HA, Jeong W, Chang TS, Park KJ, Park SJ, Yang JS, et al. Reduction of cysteine sulfinic acid by sulfiredoxin is specific to 2-cys peroxiredoxins. The Journal of Biological Chemistry.

[79] Hofmann B, Hecht HJ, Flohé

L. Peroxiredoxins. Biological Chemistry.

[80] Yan LJ, Levine RL, Sohal R. Effects of aging and hyperoxia on oxidative damage to cytochrome c in the housefly, *Musca domestica*. Free Radical Biology and Medicine. 2000;**29**(1):90-97

[81] Magwere T, West M, Riyahi K, Murphy MP, Smith RAJ, Partridge L. The effects of exogenous antioxidants

on lifespan and oxidative stress resistance in *Drosophila melanogaster*.

[82] Rebrin I, Sohal R. Comparison between the effects of aging and hyperoxia on glutathione redox state and protein mixed disulfides in *Drosophila melanogaster*. Mechanisms

Mechanisms of Ageing and Development. 2005;**127**:356-370

of Ageing and Development.

[83] Leiers B, Kampkötter A, Grevelding CG, Link CD, Johnson TE, Henkle Dührsen K. A stressresponsive glutathione S-transferase confers resistance to oxidative stress in Caenorhabditis elegans. Free Radical Biology and Medicine.

2003;**34**(11):1405-1415

Science. 1996;**273**:59-63

[85] Veal EA, Toone WM, Jones N, Morgan BA. Distinct roles

[84] Sohal RS, Weindruch R. Oxidative stress, caloric restriction, and aging.

2006;**127**:869-874

2005;**280**:3125-3128

2002;**383**(3-4):347

**30**

## Neonicotinoid Insecticides: A Threat to Pollinators

*Muhammad Imran*

### **Abstract**

Pollination is the fundamental requirement for healthier fruit set. More than 90% of flowering plant species in the hot and humid regions required pollination. Many plants species required animal pollination. Among these animals, insects play a vital role in pollination, and among the major insect pollinators, hymenopterans, honeybees, and bumblebees are regarded as the best pollinators of the crops around the world. Declining population of these important pollinators day by day is a major threat, and this declining is due to a variety of stressors. Among these possible reasons including environmental conditions, parasites, predators, malnutrition, and diseases, many researchers pointed finger at pesticides as playing a major role especially neonicotinoid. Neonicotinoids move in the environment and can be found throughout the areas where they are not applied. Neonicotinoids can drift offsite directly exposing bees and contaminate nontargeted areas when applied as spray. During plant uptake, neonicotinoid spreads through plant tissues and disrupts the physiology of pollen eaters, nectar feeders, and the insects that feed upon plant tissues. Therefore, the use of neonicotinoid is the major reason for the decline of bees in the world. So it is requested to all farmers and researchers to please find ways to kill pests not pollinators.

**Keywords:** pollinators, honeybees, bumblebees, insecticides, Neonicotinoid

#### **1. Economic importance of pollinators**

Consideration on sustainable growth generally agrees that environment still harbors much kind of living things that are potentially and unswervingly significant to mankind. Their lucrative utilize is now pending for the discovery of their worth or the formulation of how they should be propagated. There are about 25,000 species of bees [1] recognized in the world and only few play an important role in pollination producing fruits and seeds. Most of the world wide plant species depend upon animal pollination for their fertilization [2]. Among animal pollinators (any animal which transfer pollen between plants enabling fertilization and sexual reproduction from anther of male flower part to the stigma of female flower) insects provide better service of pollination [3]. Insect pollinators include bees (honey bees, bumblebees and solitary bees), flies (Carrion flies, flesh flies and hover flies), pollen wasp, ants, mosquitoes, beetles, butterflies and moths [4, 5].

Among these major insect pollinators; hymenopterans, honey bees and bumblebees are regarded as the best pollinators of the crops around the world. It has been

introduced globally due to its economic importance of honey production (honey bee) and pollination of the crops [5]. Bees are known to pollinate among 71 most familiar crops out of hundred plant species that accounts for 90% of world's food supply [6]. However, honey bees and bumblebees are the principal pollinators of the crops and it has been used successfully as pollinators in crop systems around the world [7, 8].

population dynamics of these important pollinators. There are many reason behind the decreasing population of these important pollinators such as bats, beetles, flies birds and bees, the main reasons behind this are habitat destruction [17, 18] and the introduction chemicals sprayed on crops in form of pesticides [11, 19]. Monitoring programs of NASS led by the USDA have documented the decline in managed bee's population since 1947, making them the most important example of pollinator decline in North America [11, 20]. Reasons behind the decline of these important pollinators including managed and wild bees are of mites that feed on honeybee larvae and adult body making them weak, pathogens, use of antibiotics to control these pathogen and pesticides [21–23]. Among these all factors pesticides paly vial role for the declining of population. A huge amount of these pesticides are sprayed on crops for the control of insect pest that damage crops, and bees are non-target organism on these sprayed crops. When bees visit on these sprayed crops to collect pollen and nectar become contaminated. Among these pesticides many are neurotoxic in nature such as parathion, diazinon, and carbaryl play vial role in population

However, the population of honeybee is declining day by day due to intemperate uses of pesticides [8]. Generally the bees are exposed to these pesticides; which are either used to control the parasitic mites and the pathogens attacked in the hives or to control the diseases and pest in the crops on which the bees are visited for pollen and nectar [21]. The experiments conducted in Europe and the United States found the miscellaneous range of pesticides on healthy and unhealthy bee's colonies along with their pollen, honey and bee waxes [12]. One possible cause of distressing bee mortality is the use of very active systemic insecticide called neonicotinoids [19].

Neonicotinoids; systemic insecticides, easily soluble in water but slowly break in the environment. These insecticides are absorbed by the plants through roots system and become the part of plant. The photo-degradation, half-life of neonicotinoids is about 30 4 days when exposed to sunlight [24]. It is highly toxic to insects as compare to mammals and birds because they are unable to cross the blood-brain barrier due to the lack of a charged nitrogen atom and the uncharged molecule can penetrate the insect blood–brain barrier [25]. It is derived from nicotine, which is accountable for bees decline and are highly selective neuro-active insecticides [26]. Neonicotinoids were introduced into the market in 1990 [27]. This new class of

insecticide is neurotoxic, includes imidacloprid, thiamethoxam, dinotefuran, nitenpyram, acetamiprid, thiacloprid and clothianidin [28]. The first commercial neonicotinoid was imidacloprid meanwhile clothianidin and thiamethoxam were

Neonicotinoids are systemic poisons acquire by plants through their root system and they may endured in the plants for weeks to months and mostly depends on the abiotic conditions and application rate [29, 30]. Neonicotinoids are used to protect a variety of vegetables, fruits, and major crops like corn, cotton, potato, rice, etc. against sucking insects like aphids, whiteflies, thrips, leaf- and plant hoppers [31]. In Pakistan, these insecticides are recommended for the control of sucking pests of cotton, as they are most effective against thrips, jassid, and whitefly [32, 33].

The insecticides having the neonicotinoid compounds were applied on 140 different crops in more than 120 countries around the world. The excessive use of the neonicotinoids has been reported as the major factor in declining of both domestic and wild bees. Neonicotinoids are broad spectrum insecticides and are moderately

the first two introduced insecticides in early 2000s in the market [27].

**4. Neonicotinoid, a real threat to pollinators**

*Neonicotinoid Insecticides: A Threat to Pollinators DOI: http://dx.doi.org/10.5772/intechopen.88814*

decline [21].

**33**

Many fields of current agriculture hang on pollinators. In each pollination season, these important pollinators mostly honey bees, bumblebees and native bees bring billions of U.S dollars in economic value. In several esteems, they play as a key role in the world economy [9]. But it is very important to know the real value of these important little creatures. About \$230 and \$580 billion U.S. dollars' worth of annual worldwide food production depend on the direct influence of these important pollinators [10].

Managed bees (domesticated bees by the beekeeper) are the greatest regarded pollinators in relations of agricultural economics. These pollinators (honeybees and bumblebees) can deliver pollination to almost any crop. Almond crop is entirely reliant upon honey bee pollination. Without these pollinators, yield for many fruit crops including watermelon, squash, blueberries and other fruits would be greatly reduced [11, 12]. According to the statistic presented by USDA, a honeybee colony value 100 times more to the public than to the beekeeper it mean that the value they deliver extends well beyond their actual price. Bee's pollination has aided make vegetables, nuts and fruits more accessible to consumers. There are many others species of insects called as wild species like leaf cutter bees, mason bees, alfalfa bees are not documented for their input to current agriculture. But these pollinating insects provide supplement to managed bees colonies but also pollinate some crops more professionally than their managed bees. Throughout blooming season honeybees and other native insects partner to deliver pollination for many crops. Although the economic values of their pollination is much less than managed bees, but the role of wild bees is important [11].

#### **2. Ecosystem essentials**

Preserving our indigenous flora, including wild for example bluebells, poppies, cornflowers and, along with trees, also be contingent on pollinator populations. This is much closer relationship between the declining of pollinator's population and the plant they pollinate and this relationship goes parallel throughout the world [13, 14]. It is estimated that in Europe and UK about 76% of plants that are pollinated by or called as liked by bumblebees have declined in recent decades. Pollinator's population declines spell bad news for previously declining wildflowers, which are pollinated mostly by insects and among them one fourth are endangered. In short wildlife also depends on these important pollinators, declining of wild flora means declining of wildlife including birds their shelter. Even though the insects themselves provide a significant link in the food chain as prey for other insects, birds and other animals that feed on insect [15, 16].

#### **3. Current declines in pollinator populations**

To maintain the plant genetic diversity pollination is very important for plant reproduction [12]. Due to its important role in agriculture many scientist worked on *Neonicotinoid Insecticides: A Threat to Pollinators DOI: http://dx.doi.org/10.5772/intechopen.88814*

introduced globally due to its economic importance of honey production (honey bee) and pollination of the crops [5]. Bees are known to pollinate among 71 most familiar crops out of hundred plant species that accounts for 90% of world's food supply [6]. However, honey bees and bumblebees are the principal pollinators of the crops and it has been used successfully as pollinators in crop systems around the

Many fields of current agriculture hang on pollinators. In each pollination season, these important pollinators mostly honey bees, bumblebees and native bees bring billions of U.S dollars in economic value. In several esteems, they play as a key role in the world economy [9]. But it is very important to know the real value of these important little creatures. About \$230 and \$580 billion U.S. dollars' worth of annual worldwide food production depend on the direct influence of these impor-

Managed bees (domesticated bees by the beekeeper) are the greatest regarded pollinators in relations of agricultural economics. These pollinators (honeybees and bumblebees) can deliver pollination to almost any crop. Almond crop is entirely reliant upon honey bee pollination. Without these pollinators, yield for many fruit crops including watermelon, squash, blueberries and other fruits would be greatly reduced [11, 12]. According to the statistic presented by USDA, a honeybee colony value 100 times more to the public than to the beekeeper it mean that the value they deliver extends well beyond their actual price. Bee's pollination has aided make vegetables, nuts and fruits more accessible to consumers. There are many others species of insects called as wild species like leaf cutter bees, mason bees, alfalfa bees are not documented for their input to current agriculture. But these pollinating insects provide supplement to managed bees colonies but also pollinate some crops more professionally than their managed bees. Throughout blooming season honey-

bees and other native insects partner to deliver pollination for many crops.

plant they pollinate and this relationship goes parallel throughout the world [13, 14]. It is estimated that in Europe and UK about 76% of plants that are pollinated by or called as liked by bumblebees have declined in recent decades. Pollinator's population declines spell bad news for previously declining wildflowers, which are pollinated mostly by insects and among them one fourth are endangered. In short wildlife also depends on these important pollinators, declining of wild flora means declining of wildlife including birds their shelter. Even though the insects themselves provide a significant link in the food chain as prey for other insects,

but the role of wild bees is important [11].

birds and other animals that feed on insect [15, 16].

**3. Current declines in pollinator populations**

**2. Ecosystem essentials**

**32**

Although the economic values of their pollination is much less than managed bees,

Preserving our indigenous flora, including wild for example bluebells, poppies, cornflowers and, along with trees, also be contingent on pollinator populations. This is much closer relationship between the declining of pollinator's population and the

To maintain the plant genetic diversity pollination is very important for plant reproduction [12]. Due to its important role in agriculture many scientist worked on

world [7, 8].

tant pollinators [10].

*Trends in Integrated Insect Pest Management*

population dynamics of these important pollinators. There are many reason behind the decreasing population of these important pollinators such as bats, beetles, flies birds and bees, the main reasons behind this are habitat destruction [17, 18] and the introduction chemicals sprayed on crops in form of pesticides [11, 19]. Monitoring programs of NASS led by the USDA have documented the decline in managed bee's population since 1947, making them the most important example of pollinator decline in North America [11, 20]. Reasons behind the decline of these important pollinators including managed and wild bees are of mites that feed on honeybee larvae and adult body making them weak, pathogens, use of antibiotics to control these pathogen and pesticides [21–23]. Among these all factors pesticides paly vial role for the declining of population. A huge amount of these pesticides are sprayed on crops for the control of insect pest that damage crops, and bees are non-target organism on these sprayed crops. When bees visit on these sprayed crops to collect pollen and nectar become contaminated. Among these pesticides many are neurotoxic in nature such as parathion, diazinon, and carbaryl play vial role in population decline [21].

However, the population of honeybee is declining day by day due to intemperate uses of pesticides [8]. Generally the bees are exposed to these pesticides; which are either used to control the parasitic mites and the pathogens attacked in the hives or to control the diseases and pest in the crops on which the bees are visited for pollen and nectar [21]. The experiments conducted in Europe and the United States found the miscellaneous range of pesticides on healthy and unhealthy bee's colonies along with their pollen, honey and bee waxes [12]. One possible cause of distressing bee mortality is the use of very active systemic insecticide called neonicotinoids [19].

## **4. Neonicotinoid, a real threat to pollinators**

Neonicotinoids; systemic insecticides, easily soluble in water but slowly break in the environment. These insecticides are absorbed by the plants through roots system and become the part of plant. The photo-degradation, half-life of neonicotinoids is about 30 4 days when exposed to sunlight [24]. It is highly toxic to insects as compare to mammals and birds because they are unable to cross the blood-brain barrier due to the lack of a charged nitrogen atom and the uncharged molecule can penetrate the insect blood–brain barrier [25]. It is derived from nicotine, which is accountable for bees decline and are highly selective neuro-active insecticides [26].

Neonicotinoids were introduced into the market in 1990 [27]. This new class of insecticide is neurotoxic, includes imidacloprid, thiamethoxam, dinotefuran, nitenpyram, acetamiprid, thiacloprid and clothianidin [28]. The first commercial neonicotinoid was imidacloprid meanwhile clothianidin and thiamethoxam were the first two introduced insecticides in early 2000s in the market [27]. Neonicotinoids are systemic poisons acquire by plants through their root system and they may endured in the plants for weeks to months and mostly depends on the abiotic conditions and application rate [29, 30]. Neonicotinoids are used to protect a variety of vegetables, fruits, and major crops like corn, cotton, potato, rice, etc. against sucking insects like aphids, whiteflies, thrips, leaf- and plant hoppers [31]. In Pakistan, these insecticides are recommended for the control of sucking pests of cotton, as they are most effective against thrips, jassid, and whitefly [32, 33].

The insecticides having the neonicotinoid compounds were applied on 140 different crops in more than 120 countries around the world. The excessive use of the neonicotinoids has been reported as the major factor in declining of both domestic and wild bees. Neonicotinoids are broad spectrum insecticides and are moderately

to highly effective and toxic to bees that depends upon the presence of active ingredient in the insecticides [34]. Neonicotinoids are mainly used in seed and soil treatment and sometimes they also directly applied to plant foliage [27]. Many of the neonicotinoids are highly toxic to the insect pollinators and also to the honey bees. It changes the behavior that results in the behavioral disturbances, orientation difficulties and impairment of social activities [35–41].

Among distinctive behaviors of honey bees, foraging is one of idiosyncratic behavior of the *Apis mellifera*. This type of behavior is like an association between the bee

After World War II, we started using pesticides on a large scale, and this became necessary because of the monocultures that put out a feast for crop pest. Recently, researchers from Penn State University has started looking at the pesticides residue in the loads of pollen that bees carry home as food, and they have found that every batch of pollen that honeybee collects has at least six detectable pesticides in it, and this includes every class of insecticides, herbicides, fungicides and even inert and unlabeled ingredients that are part of the pesticides formulation that can be more

toxic than the active ingredient. One of these classes of insecticides, the

neonicotinoids is making headlines around the world right now you have probably heard about it. This is the new class of insecticides, it move through the plant so that a crop pest, a leaf eating insect would take a bite of plant and get a lethal dose and die. In most agricultural settings, on most of our farms it's only the seed that's coated with insecticides and so a smaller concentration move through the plant and gets into the pollen and nectar, and if a bee consumes this lower dose either nothing happens or the bee becomes intoxicated and disoriented and she may not find her

Every one of us needs to behave a little bit more like a bee society, and insect society, where each of our individual actions can contribute to grand solution and emergent property. So let the small act of planting flowers and keeping them free of pesticides be the driver to large scale change. Please find the ways to kill pest

Department of Entomology, University of the Poonch, Rawalakot,

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*Address all correspondence to: imran.bees@gmail.com

colonies and the ambient environment [59].

*Neonicotinoid Insecticides: A Threat to Pollinators DOI: http://dx.doi.org/10.5772/intechopen.88814*

**5.1 Strategies to conserve the pollinators**

**5. Conclusion**

way to home.

not bees.

**Author details**

Muhammad Imran

**35**

Azad Jammu and Kashmir, Pakistan

provided the original work is properly cited.

Neonicotinoids also affects the CNS (central nervous system) of the insects as it binds agonistically to the post-synaptic nicotinic acetylcholine receptors that results in the spontaneous discharge of nerve impulses and eventual failure of the neuron to propagate any signal [42]. The neonicotinoids and their metabolites have the capability to persistent in the soil and aquatic sediments [43] and their persistence at shallow depths could increase the chances of aquatic life and other wildlife including honey bees could get exposed to the insecticide [44].

The neonicotinoids are considered to be most effective insecticide other than organophosphates and carbamates [45]. Imidacloprid is the most widely used insecticide and has drawn more attention on the health of bees than other neonicotinoids. More than 400 products of this insecticides accounting for about 15th of the globally insecticide marketed [46]. Honeybees are exposed to neonicotinoids in different ways from ingestion, contact and inhalation [47]. The pollen foragers which are different from the nectar foragers; they do not consume pollen by itself but it brings to the hives to consumed for the nurse bees and larvae hence the nurse bees and larvae exposed to neonicotinoids and their metabolites [48].

The forager bees used honey from their hive before they leave for foraging. It depends upon the distance that it will travel from their hive to foraging field, the forager bees have to consume more or less amount of nectar or honey from their hive for energy and foraging. Therefore the foragers may ingest more or less amount of residues of neonicotinoids [49]. The colony become contaminated when the worker bees come into contact with pollen or nectar contaminated with neonicotinoid and transport them to the hive, where they are normally observed in honey and bee bread [50, 51]. Bee hives made up of trees treated with neonicotinoids could have residues which may cause trouble for bees [52]. Oral route of neonicotinoid uptake is highest in forager honeybees, winter honeybees and larvae [53, 54]. Serious pests of citrus in Pakistan and other Asian countries are mostly control by using various classes of neonicotinoids. The foraging bees visiting citrus flowers get exposed to the residues of neonicotinoids which are responsible for damaging their physiology [55].

Neonicotinoids increased worker mortality and queenlessness over time. The toxicity of the neonicotinoids increases when it encountered with fungicides. In corn growing areas, the health of honey bees are reduced when are exposed to neonicotinoids in the field [56]. The irretrievable and cumulative damage to central nervous system of insects is often caused by neonicotinoid insecticides. There is no safe level of neonicotinoids and even only a very minute quantity of these systemic poisons could have long lasting drastic effects [57]. The activities of the acetyl cholinesterase is increased by the thiamethoxam at each developmental stages of the insects and the activities of glutathione-S- transferase and carboxyl esterase para increases at the pupal stages and reduced the survival of larvae and pupa that results in the decreasing of percentage emergence of honeybees [58]. The effects of thiamethoxam cause the reduction of forager bees returning to the hive [59]. When honey bees are exposed to a sub-lethal doses of imidacloprid and clothianidin that results in the reduction of foraging activities as well as longer foraging flights [60]. The bees become detract when it became exposed to nonlethal doses to thiamethoxam and causes high mortality at levels that may collapse the colony.

Among distinctive behaviors of honey bees, foraging is one of idiosyncratic behavior of the *Apis mellifera*. This type of behavior is like an association between the bee colonies and the ambient environment [59].

## **5. Conclusion**

to highly effective and toxic to bees that depends upon the presence of active ingredient in the insecticides [34]. Neonicotinoids are mainly used in seed and soil treatment and sometimes they also directly applied to plant foliage [27]. Many of the neonicotinoids are highly toxic to the insect pollinators and also to the honey bees. It changes the behavior that results in the behavioral disturbances, orientation

Neonicotinoids also affects the CNS (central nervous system) of the insects as it binds agonistically to the post-synaptic nicotinic acetylcholine receptors that results in the spontaneous discharge of nerve impulses and eventual failure of the neuron to propagate any signal [42]. The neonicotinoids and their metabolites have the capability to persistent in the soil and aquatic sediments [43] and their persistence at shallow depths could increase the chances of aquatic life and other wildlife

The neonicotinoids are considered to be most effective insecticide other than organophosphates and carbamates [45]. Imidacloprid is the most widely used insecticide and has drawn more attention on the health of bees than other neonicotinoids. More than 400 products of this insecticides accounting for about

neonicotinoids in different ways from ingestion, contact and inhalation [47]. The pollen foragers which are different from the nectar foragers; they do not consume pollen by itself but it brings to the hives to consumed for the nurse bees and larvae hence the nurse bees and larvae exposed to neonicotinoids and their

The forager bees used honey from their hive before they leave for foraging. It depends upon the distance that it will travel from their hive to foraging field, the forager bees have to consume more or less amount of nectar or honey from their hive for energy and foraging. Therefore the foragers may ingest more or less amount of residues of neonicotinoids [49]. The colony become contaminated when

neonicotinoid and transport them to the hive, where they are normally observed in

Neonicotinoids increased worker mortality and queenlessness over time. The toxicity of the neonicotinoids increases when it encountered with fungicides. In corn growing areas, the health of honey bees are reduced when are exposed to neonicotinoids in the field [56]. The irretrievable and cumulative damage to central nervous system of insects is often caused by neonicotinoid insecticides. There is no safe level of neonicotinoids and even only a very minute quantity of these systemic poisons could have long lasting drastic effects [57]. The activities of the acetyl cholinesterase is increased by the thiamethoxam at each developmental stages of the insects and the activities of glutathione-S- transferase and carboxyl esterase para increases at the pupal stages and reduced the survival of larvae and pupa that results in the decreasing of percentage emergence of honeybees [58]. The effects of thiamethoxam cause the reduction of forager bees returning to the hive [59]. When honey bees are exposed to a sub-lethal doses of imidacloprid and clothianidin that results in the reduction of foraging activities as well as longer foraging flights [60].

neonicotinoids could have residues which may cause trouble for bees [52]. Oral route of neonicotinoid uptake is highest in forager honeybees, winter honeybees and larvae [53, 54]. Serious pests of citrus in Pakistan and other Asian countries are mostly control by using various classes of neonicotinoids. The foraging bees visiting citrus flowers get exposed to the residues of neonicotinoids which are responsible

the worker bees come into contact with pollen or nectar contaminated with

honey and bee bread [50, 51]. Bee hives made up of trees treated with

The bees become detract when it became exposed to nonlethal doses to

thiamethoxam and causes high mortality at levels that may collapse the colony.

15th of the globally insecticide marketed [46]. Honeybees are exposed to

difficulties and impairment of social activities [35–41].

*Trends in Integrated Insect Pest Management*

metabolites [48].

**34**

for damaging their physiology [55].

including honey bees could get exposed to the insecticide [44].

After World War II, we started using pesticides on a large scale, and this became necessary because of the monocultures that put out a feast for crop pest. Recently, researchers from Penn State University has started looking at the pesticides residue in the loads of pollen that bees carry home as food, and they have found that every batch of pollen that honeybee collects has at least six detectable pesticides in it, and this includes every class of insecticides, herbicides, fungicides and even inert and unlabeled ingredients that are part of the pesticides formulation that can be more toxic than the active ingredient. One of these classes of insecticides, the neonicotinoids is making headlines around the world right now you have probably heard about it. This is the new class of insecticides, it move through the plant so that a crop pest, a leaf eating insect would take a bite of plant and get a lethal dose and die. In most agricultural settings, on most of our farms it's only the seed that's coated with insecticides and so a smaller concentration move through the plant and gets into the pollen and nectar, and if a bee consumes this lower dose either nothing happens or the bee becomes intoxicated and disoriented and she may not find her way to home.

## **5.1 Strategies to conserve the pollinators**

Every one of us needs to behave a little bit more like a bee society, and insect society, where each of our individual actions can contribute to grand solution and emergent property. So let the small act of planting flowers and keeping them free of pesticides be the driver to large scale change. Please find the ways to kill pest not bees.

## **Author details**

Muhammad Imran Department of Entomology, University of the Poonch, Rawalakot, Azad Jammu and Kashmir, Pakistan

\*Address all correspondence to: imran.bees@gmail.com

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

## **References**

[1] Michener CD. The Bees of the World. Baltimore: John Hopkins, London Press; 2000. p. 873

[2] Fulton M, Hodges SA. Floral isolation between *Aquilegia formosa* and *A. pubescens*. Proceedings of the Royal Society of London. 1999;**266**:2247-2252

[3] Hodges SA, Whittall JB, Fulton M, Yang JY. Genetics of floral traits influencing reproductive isolation between Aquilegia *formosa* and *A. pubescens*. American Naturalist. 2002; **159**:51-60

[4] Moreti ACCC, Silva ECA, Alves MLTMF. Observações sobre a polinização entomófila da cultura da soja (Glycine max Merril). Boletim da Indústria Animal. 1998;**55**:91-94

[5] Winfree R, Williams NM, Gaines H, Ascher JS, Kremen C. Wild bee pollinators provide the majority of crop visitation across land-use gradients in New Jersey and Pennsylvania, USA. Journal of Applied Ecology. 2008;**45**: 793-802

[6] Gallaia N, Sallesc JM, Setteled J, Vaissierea BE. Economic valuation of the vulnerability of world agriculture confronted with pollinator decline. Ecological Economics. 2009;**68**:810-821

[7] Artz DR, Hsu CI, Nault B. Influence of honey bee, *Apis mellifera*, hives and field size on foraging activity of native bee species in pumpkin fields. Environmental Entomology. 2011;**40**: 1144-1158

[8] Morse RA, Calderone NW. The value of honey bee as pollinator of U.S. crops. Bee Culture. 2000;**128**:1-15

[9] Kremen C, Williams NM, Aizen MA, Herren BG, LeBuhn G, Minckley R, et al. Pollination and other ecosystem services produced by mobile organisms:

A conceptual framework for the effects of land-use change. Ecology Letters. 2007;**10**:299-314

Serrano'. Ecological Applications. 1994;**4**:

*Neonicotinoid Insecticides: A Threat to Pollinators DOI: http://dx.doi.org/10.5772/intechopen.88814*

> [28] Jeschke JM. Across islands and continents, mammals are more

[29] Bromilow RH, Chamberlain K, Evans AA. Physiochemical aspects of phloem transclucation of herbicides. Weed Science. 1990;**38**:305-314

[30] Laurent FM, Rathahao E. Distribution of imidacloprid in sunflowers (*Helianthus annuus*) following seed treatment. Journal of Agricultural Food Chemistry. 2003;**51**:

[31] Elbert A, Haas M, Springer B, Thielertf W, Nauen R. Applied aspects of neonicotinoid uses in crop protection. Pest Management Science. 2008;**64**:

[32] Bethke AJ, Redak RA. Effect of imidacloprid on the silver leaf whitefly, *Bemisia argentifolii* bellows and Perring (Homoptera: Aleyrodidae), and whitefly parasitism. Annals of Applied

Biology. 2008;**130**:397-407

[33] Lopez JR, Jr D, Fritz BK,

Science. 2008;**12**:188-194

2011;**59**:2897-2908

Latheef MA, Lan Y, Martin DE, et al. Evaluation of toxicity of selected insecticides against thrips on cotton in laboratory bioassays. Journal of Cotton

[34] Jeschke P, Nauen R, Schindler M, Elbert A. Overview of the status and global strategy for neonicotinoids. Journal of Agricultural Food Chemistry.

[35] Guez D, Suchail S, Gauthier M, Maleszka R, Belzunces LP. Contrasting effects of imidacloprid on habituation in 7- and 8- day - old honeybees (*Apis mellifera*). Neurobiology Learning

Memory. 2001;**76**:183-191

[36] Bortolotti L, Montanari R, Marcelino J, Medrzycki P, Aini S, Porrini C. Effects of sub-lethal

8005-8010

1099-1105

successful invaders than birds. Diversity and Distributions. 2008;**14**:913-916

[19] Kevan PG. Forest application of the insecticide fenitrothion and its effect on wild bee pollinators (Hymenoptera: Apoidea) of lowbush blueberries (Vaccinium spp.) in Southern New Brunswick, Canada. Biological Conservation. 1975;**7**:301-309

[20] (NASS) National Agricultural Statistics Service. Honey. Washington, D.C.: United States Department of Agriculture; 1976-2008. Available from: http://www.nass.usda.gov, Dec 2008

[21] Johansen CA, Mayer DF. Pollinator

[22] Morse RA, Flottum K. Honey Bee Pests, Predators, and Diseases. Medina, OH: A.I. Root Company; 1997. p. 454

Henderson CE, Morse RA. Tracheal mites. In: Morse RA, Flottum K, editors.

[24] Cressey D. Europe debates risk to bees. Nature. 2013;**496**:408-409

[25] Izuru Y. Nicotine to nicotinoids. In:

Honey Bee Pests, Predators, and Diseases. 3rd ed. Medina, OH: A.I. Root

Company; 1997. pp. 253-278

Yamamoto I, Casida J, editors. Nicotinoid Insecticides and the Nicotinic Acetylcholine Receptor. Springer-Verlag; 1999. pp. 3-27

[26] Cresswell JEE, Desneux N, Vangelsdrop D. Dietary traces of neonicotinoid pesticides are a cause of population declines in honeybees. Pest Management Science. 2012;**68**:819-827

[27] Tomizawa M, Casida J.

Review of Pharmacology and Toxicology. 2005;**54**:247-268

**37**

Neonicotinoid insecticide toxicology: Mechanisms of selective action. Annual

Protection: A Bee and Pesticide Handbook. Cheshire, CT: Wicwas

Press; 1990. p. 322

[23] Wilson WT, Pettis JS,

378-392

[10] Vanbergen AJ, Insect Pollinators Initiative. Threats to an ecosystem service: Pressures on pollinators. Frontiers in Ecology and the Environment. 2013;**11**:251-259

[11] Berenbaum M, Bernhardt P, Buchmann S, Calderone NW, et al. Status of Pollinators in North America. Washington, D.C: The National Academies Press; 2007. p. 322

[12] Delaplane KS, Mayer DF. Crop Pollination by Bees. New York: CABI Publishing; 2000. p. 344

[13] Morales CL, Aizen MA. Does invasion of exotic plants promote invasion of exotic flower visitors? A case study from the temperate forests of the southern Andes. Biological Invasions. 2002;**4**:87-100

[14] Parker IM. Pollinator limitation of *Cytisus scoparius* (scotch broom), an invasive exotic shrub. Ecology. 1997;**78**: 1457-1470

[15] Levine JM, Vilà M, Antonio CM, Dukes JS, Grigulis K, Lavorel S. Mechanisms underlying the impacts of exotic plant invasions. Proceedings of the Royal Society of London. Series B, Biological Sciences. 2003;**270**:775-781

[16] Richardson DM. Plant invasion ecology dispatches from the front line. Divers. Diversity and Distributions. 2004;**10**:315-319

[17] Stephen WP. Alfalfa pollination in Manitoba. Journal of Economic Entomology. 1995;**48**:543-548

[18] Aizen MA, Feinsinger P. Habitat fragmentation, native insect pollinators, and feral honey bees in argentine 'Chaco *Neonicotinoid Insecticides: A Threat to Pollinators DOI: http://dx.doi.org/10.5772/intechopen.88814*

Serrano'. Ecological Applications. 1994;**4**: 378-392

**References**

2000. p. 873

**159**:51-60

793-802

1144-1158

**36**

[1] Michener CD. The Bees of the World. Baltimore: John Hopkins, London Press;

*Trends in Integrated Insect Pest Management*

A conceptual framework for the effects of land-use change. Ecology Letters.

[10] Vanbergen AJ, Insect Pollinators Initiative. Threats to an ecosystem service: Pressures on pollinators. Frontiers in Ecology and the Environment. 2013;**11**:251-259

[11] Berenbaum M, Bernhardt P, Buchmann S, Calderone NW, et al. Status of Pollinators in North America. Washington, D.C: The National Academies Press; 2007. p. 322

[12] Delaplane KS, Mayer DF. Crop Pollination by Bees. New York: CABI

[13] Morales CL, Aizen MA. Does invasion of exotic plants promote invasion of exotic flower visitors? A case study from the temperate forests of the southern Andes. Biological Invasions. 2002;**4**:87-100

[14] Parker IM. Pollinator limitation of *Cytisus scoparius* (scotch broom), an invasive exotic shrub. Ecology. 1997;**78**:

[15] Levine JM, Vilà M, Antonio CM, Dukes JS, Grigulis K, Lavorel S. Mechanisms underlying the impacts of exotic plant invasions. Proceedings of the Royal Society of London. Series B, Biological Sciences. 2003;**270**:775-781

[16] Richardson DM. Plant invasion ecology dispatches from the front line. Divers. Diversity and Distributions.

[17] Stephen WP. Alfalfa pollination in Manitoba. Journal of Economic Entomology. 1995;**48**:543-548

[18] Aizen MA, Feinsinger P. Habitat fragmentation, native insect pollinators, and feral honey bees in argentine 'Chaco

Publishing; 2000. p. 344

1457-1470

2004;**10**:315-319

2007;**10**:299-314

[2] Fulton M, Hodges SA. Floral isolation between *Aquilegia formosa* and *A. pubescens*. Proceedings of the Royal Society of London. 1999;**266**:2247-2252

[3] Hodges SA, Whittall JB, Fulton M, Yang JY. Genetics of floral traits influencing reproductive isolation between Aquilegia *formosa* and *A. pubescens*. American Naturalist. 2002;

[5] Winfree R, Williams NM, Gaines H,

pollinators provide the majority of crop visitation across land-use gradients in New Jersey and Pennsylvania, USA. Journal of Applied Ecology. 2008;**45**:

[6] Gallaia N, Sallesc JM, Setteled J, Vaissierea BE. Economic valuation of the vulnerability of world agriculture confronted with pollinator decline. Ecological Economics. 2009;**68**:810-821

[7] Artz DR, Hsu CI, Nault B. Influence of honey bee, *Apis mellifera*, hives and field size on foraging activity of native

Environmental Entomology. 2011;**40**:

[8] Morse RA, Calderone NW. The value of honey bee as pollinator of U.S. crops.

[9] Kremen C, Williams NM, Aizen MA, Herren BG, LeBuhn G, Minckley R, et al. Pollination and other ecosystem services produced by mobile organisms:

bee species in pumpkin fields.

Bee Culture. 2000;**128**:1-15

Ascher JS, Kremen C. Wild bee

[4] Moreti ACCC, Silva ECA, Alves MLTMF. Observações sobre a polinização entomófila da cultura da soja (Glycine max Merril). Boletim da Indústria Animal. 1998;**55**:91-94

[19] Kevan PG. Forest application of the insecticide fenitrothion and its effect on wild bee pollinators (Hymenoptera: Apoidea) of lowbush blueberries (Vaccinium spp.) in Southern New Brunswick, Canada. Biological Conservation. 1975;**7**:301-309

[20] (NASS) National Agricultural Statistics Service. Honey. Washington, D.C.: United States Department of Agriculture; 1976-2008. Available from: http://www.nass.usda.gov, Dec 2008

[21] Johansen CA, Mayer DF. Pollinator Protection: A Bee and Pesticide Handbook. Cheshire, CT: Wicwas Press; 1990. p. 322

[22] Morse RA, Flottum K. Honey Bee Pests, Predators, and Diseases. Medina, OH: A.I. Root Company; 1997. p. 454

[23] Wilson WT, Pettis JS, Henderson CE, Morse RA. Tracheal mites. In: Morse RA, Flottum K, editors. Honey Bee Pests, Predators, and Diseases. 3rd ed. Medina, OH: A.I. Root Company; 1997. pp. 253-278

[24] Cressey D. Europe debates risk to bees. Nature. 2013;**496**:408-409

[25] Izuru Y. Nicotine to nicotinoids. In: Yamamoto I, Casida J, editors. Nicotinoid Insecticides and the Nicotinic Acetylcholine Receptor. Springer-Verlag; 1999. pp. 3-27

[26] Cresswell JEE, Desneux N, Vangelsdrop D. Dietary traces of neonicotinoid pesticides are a cause of population declines in honeybees. Pest Management Science. 2012;**68**:819-827

[27] Tomizawa M, Casida J. Neonicotinoid insecticide toxicology: Mechanisms of selective action. Annual Review of Pharmacology and Toxicology. 2005;**54**:247-268

[28] Jeschke JM. Across islands and continents, mammals are more successful invaders than birds. Diversity and Distributions. 2008;**14**:913-916

[29] Bromilow RH, Chamberlain K, Evans AA. Physiochemical aspects of phloem transclucation of herbicides. Weed Science. 1990;**38**:305-314

[30] Laurent FM, Rathahao E. Distribution of imidacloprid in sunflowers (*Helianthus annuus*) following seed treatment. Journal of Agricultural Food Chemistry. 2003;**51**: 8005-8010

[31] Elbert A, Haas M, Springer B, Thielertf W, Nauen R. Applied aspects of neonicotinoid uses in crop protection. Pest Management Science. 2008;**64**: 1099-1105

[32] Bethke AJ, Redak RA. Effect of imidacloprid on the silver leaf whitefly, *Bemisia argentifolii* bellows and Perring (Homoptera: Aleyrodidae), and whitefly parasitism. Annals of Applied Biology. 2008;**130**:397-407

[33] Lopez JR, Jr D, Fritz BK, Latheef MA, Lan Y, Martin DE, et al. Evaluation of toxicity of selected insecticides against thrips on cotton in laboratory bioassays. Journal of Cotton Science. 2008;**12**:188-194

[34] Jeschke P, Nauen R, Schindler M, Elbert A. Overview of the status and global strategy for neonicotinoids. Journal of Agricultural Food Chemistry. 2011;**59**:2897-2908

[35] Guez D, Suchail S, Gauthier M, Maleszka R, Belzunces LP. Contrasting effects of imidacloprid on habituation in 7- and 8- day - old honeybees (*Apis mellifera*). Neurobiology Learning Memory. 2001;**76**:183-191

[36] Bortolotti L, Montanari R, Marcelino J, Medrzycki P, Aini S, Porrini C. Effects of sub-lethal

imidacloprid doses on the homing rate and foraging activity of honey bees. Bulletin of Insectology. 2003;**56**:63-67

[37] Medrzycki P, Montanari R, Bortolotti L, Sabatini AG, Maini S, Porrini C. Effects of Imidacloprid administered in sub-lethal doses on honey bees' behaviour. Laboratory tests. In: Proceedings of the 8th International Symposium "Hazards of Pesticides to Bees", September 4–6, 2002, Bologna, Italy (Eds). Bulletin of Insectology. Vol. 56. 2003. pp. 59-62

[38] Decourtye A, Armengaud C, Renou M, Devillers J, Cluzeau S, Gauthier M, et al. Imidacloprid impairs memory and brain metabolism in the honeybee (*Apis mellifera*). Pesticide Biochemistry and Physiology. 2004;**78**: 83-92

[39] Desneux N, Decourtye A, Delpuech JM. The sublethal effects of pesticides on beneficial arthropods. Annual Review of Entomology. 2007;**52**: 81-106

[40] Hassani AKEI, Dacher M, Gary V, Lambin M, Gauthier M, Armengaud C. Effects of sublethal doses of acetamiprid and thiamethoxam on the behavior of the honeybee (*Apis mellifera*). Archives Environmental Contamination Toxicology. 2008;**54**:653-666

[41] Maini S, Medrzycki P, Porrini C. The puzzle of honey bee losses: A brief review. Bulletin of Insectology. 2010;**63**: 153-160

[42] Matsuda K, Sattelle DB. Mechanism of selective actions of neonicotinoids on insect acetylcholine receptors. In: Clark JM, Ohkawa H, editors. New Discoveries in Agrochemicals: American Chemical Society Symposium Series. Oxford, UK: Oxford University Press; 2005. pp. 172-183

[43] Doering J, Maus C, Schoening R. Residues of imidacloprid in blossom

samples of rhododendron sp after soil treatment in the field application. Environmental Chemistry. 2004;**62**: 483-494

[51] Genersch E, Ohe VDW, Kaatz H, Schroeder A, Otten C, Buechler R, et al. The German bee monitoring project: A

*Neonicotinoid Insecticides: A Threat to Pollinators DOI: http://dx.doi.org/10.5772/intechopen.88814*

> [59] Henry M, Beguin M, Requier F, Rollin O, Odoux JF, Aupinel P, et al. A common pesticide decreases foraging success and survival in honey bees.

Science. 2012;**336**:348-350

2012;**43**:218-225

[60] Schneider S, Eisenhardt D, Rademacher E. Sublethal effects of oxalic acid on *Apis mellifera*

(Hymenoptera: Apidae): Changes in behaviour and longevity. Apidologie.

periodically high winter losses of honey bee colonies. Apidologie. 2010;**41**:332-352

[52] Beekman M, Ratnieks FLW. Long range foraging by honey bees *Apis mellifera*. Functional Ecology. 2000;**14**:

[53] Chauzat MP, Faucon JP, Martel AC, Lachaize CN, Aubert M, et al. Journal of Economical Entomology. 2006;**99**:

[54] Reetz JE, Zühlke S, Spiteller M, Wallner K. Neonicotinoid insecticides translocated in guttated droplets of seedtreated maize and wheat: A threat to honeybees? Apidologie. 2011;**42**:

[55] Khan AA, Afzal M, Raza AM, Khan AM, Iqbal J, Tahir HM, et al. Toxicity of botanicals and selective insecticides to Asian citrus psylla, *Diaphorina citri* K.(Homoptera: Psyllidae) in laboratory conditions. Jokull Journal. 2013;**63**:52-72

[56] Tsvetkov N, Robert OS, Sood K, Patel HS, Malena DA, Gajiwala PH, et al. Chronic exposure to neonicotinoids reduces honey bee health near corn crops. Science. 2017;**356**:1395-1397

[57] Tennekes HA. The significance of the Druckrey-Küpfmüller equation for

neonicotinoid insecticides to arthropods

risk assessment–the toxicity of

is reinforced by exposure time. Toxicology. 2010;**276**:1-4

[58] Tavares DA, Dussaubat C, Kretzschmar A, Carvalho SM, Zacarin ECMS, Malaspina O, et al. Exposure of larvae to thiamethoxam affects the survival and physiology of the honey bee at post-embryonic stages. Environmental Pollution, Elsevier. 2017;

**229**:386-393

**39**

long term study to understand

490-496

253-262

596-606

[44] Lu Z, Jonathan K, Challis WCS. Quantum yields for direct photolysis of neonicotinoid insecticides in water: Implications for exposure to non-target aquatic organisms. Environmental Science and Technology. 2015;**2**:188-192

[45] Bonmatin JM, Marchand PA, Charvet R, Moineau I, Bengsch ER, Colin ME. Quantification of Imidacloprid uptake in maize crop. Journal of Agricultural and Food Chemistry. 2005;**53**:5336-5341

[46] Chen M, Lin T, Collins E, Lu MC. Simultaneous determination of residues in pollen and high fructose corn syrup from eight neonicotinoid insecticides by liquid chromatography-tandem mass spectrometry. Analytical and Bio analytical Chemistry. 2013;**405**: 9251-9264

[47] Girolami KM, Kahng SW, Hilker KA, Girolami PA. Differential reinforcement of high rate behavior to increase the pace of self-feeding. Behavioral Interventions. 2009;**24**:17-22

[48] Rortais A, Amold G, Halm MP, Briens TF. Modes of honey bee exposure to systemic insecticides: Estimated amounts of contaminated pollen and nectar consumed by different categories of bees in France. Apidologie. 2005;**36**: 71-83

[49] Maxim L, Slujis VD. Seed dressing systemic insecticide and honeybees. European Environment Agency. 2013; **376**:1-17

[50] Blacquiere T, Smagghe G, Van Gestel CA, Mommaerts V. Neonicotinoids in bees: A review on concentrations, side-effects and risk assessment. Ecotoxicology. 2012;**21**: 973-992

*Neonicotinoid Insecticides: A Threat to Pollinators DOI: http://dx.doi.org/10.5772/intechopen.88814*

[51] Genersch E, Ohe VDW, Kaatz H, Schroeder A, Otten C, Buechler R, et al. The German bee monitoring project: A long term study to understand periodically high winter losses of honey bee colonies. Apidologie. 2010;**41**:332-352

imidacloprid doses on the homing rate and foraging activity of honey bees. Bulletin of Insectology. 2003;**56**:63-67

*Trends in Integrated Insect Pest Management*

samples of rhododendron sp after soil treatment in the field application. Environmental Chemistry. 2004;**62**:

[44] Lu Z, Jonathan K, Challis WCS. Quantum yields for direct photolysis of neonicotinoid insecticides in water: Implications for exposure to non-target aquatic organisms. Environmental Science and Technology. 2015;**2**:188-192

[45] Bonmatin JM, Marchand PA, Charvet R, Moineau I, Bengsch ER, Colin ME. Quantification of Imidacloprid uptake in maize crop. Journal of Agricultural and Food Chemistry. 2005;**53**:5336-5341

[46] Chen M, Lin T, Collins E, Lu MC. Simultaneous determination of residues in pollen and high fructose corn syrup from eight neonicotinoid insecticides by liquid chromatography-tandem mass spectrometry. Analytical and Bio analytical Chemistry. 2013;**405**:

[47] Girolami KM, Kahng SW, Hilker KA, Girolami PA. Differential reinforcement of high rate behavior to increase the pace of self-feeding. Behavioral Interventions. 2009;**24**:17-22

[48] Rortais A, Amold G, Halm MP, Briens TF. Modes of honey bee exposure to systemic insecticides: Estimated amounts of contaminated pollen and nectar consumed by different categories of bees in France. Apidologie. 2005;**36**:

[49] Maxim L, Slujis VD. Seed dressing systemic insecticide and honeybees. European Environment Agency. 2013;

[50] Blacquiere T, Smagghe G, Van

Neonicotinoids in bees: A review on concentrations, side-effects and risk assessment. Ecotoxicology. 2012;**21**:

Gestel CA, Mommaerts V.

483-494

9251-9264

71-83

**376**:1-17

973-992

[37] Medrzycki P, Montanari R, Bortolotti L, Sabatini AG, Maini S, Porrini C. Effects of Imidacloprid administered in sub-lethal doses on honey bees' behaviour. Laboratory tests. In: Proceedings of the 8th International Symposium "Hazards of Pesticides to Bees", September 4–6, 2002, Bologna, Italy (Eds). Bulletin of Insectology. Vol.

[38] Decourtye A, Armengaud C, Renou M, Devillers J, Cluzeau S, Gauthier M, et al. Imidacloprid impairs memory and brain metabolism in the honeybee (*Apis mellifera*). Pesticide Biochemistry and Physiology. 2004;**78**:

[39] Desneux N, Decourtye A,

Environmental Contamination Toxicology. 2008;**54**:653-666

[41] Maini S, Medrzycki P, Porrini C. The puzzle of honey bee losses: A brief review. Bulletin of Insectology. 2010;**63**:

[42] Matsuda K, Sattelle DB. Mechanism of selective actions of neonicotinoids on insect acetylcholine receptors. In: Clark JM, Ohkawa H, editors. New Discoveries in Agrochemicals: American Chemical Society Symposium Series. Oxford, UK: Oxford University Press;

[43] Doering J, Maus C, Schoening R. Residues of imidacloprid in blossom

Delpuech JM. The sublethal effects of pesticides on beneficial arthropods. Annual Review of Entomology. 2007;**52**:

[40] Hassani AKEI, Dacher M, Gary V, Lambin M, Gauthier M, Armengaud C. Effects of sublethal doses of acetamiprid and thiamethoxam on the behavior of the honeybee (*Apis mellifera*). Archives

56. 2003. pp. 59-62

83-92

81-106

153-160

2005. pp. 172-183

**38**

[52] Beekman M, Ratnieks FLW. Long range foraging by honey bees *Apis mellifera*. Functional Ecology. 2000;**14**: 490-496

[53] Chauzat MP, Faucon JP, Martel AC, Lachaize CN, Aubert M, et al. Journal of Economical Entomology. 2006;**99**: 253-262

[54] Reetz JE, Zühlke S, Spiteller M, Wallner K. Neonicotinoid insecticides translocated in guttated droplets of seedtreated maize and wheat: A threat to honeybees? Apidologie. 2011;**42**: 596-606

[55] Khan AA, Afzal M, Raza AM, Khan AM, Iqbal J, Tahir HM, et al. Toxicity of botanicals and selective insecticides to Asian citrus psylla, *Diaphorina citri* K.(Homoptera: Psyllidae) in laboratory conditions. Jokull Journal. 2013;**63**:52-72

[56] Tsvetkov N, Robert OS, Sood K, Patel HS, Malena DA, Gajiwala PH, et al. Chronic exposure to neonicotinoids reduces honey bee health near corn crops. Science. 2017;**356**:1395-1397

[57] Tennekes HA. The significance of the Druckrey-Küpfmüller equation for risk assessment–the toxicity of neonicotinoid insecticides to arthropods is reinforced by exposure time. Toxicology. 2010;**276**:1-4

[58] Tavares DA, Dussaubat C, Kretzschmar A, Carvalho SM, Zacarin ECMS, Malaspina O, et al. Exposure of larvae to thiamethoxam affects the survival and physiology of the honey bee at post-embryonic stages. Environmental Pollution, Elsevier. 2017; **229**:386-393

[59] Henry M, Beguin M, Requier F, Rollin O, Odoux JF, Aupinel P, et al. A common pesticide decreases foraging success and survival in honey bees. Science. 2012;**336**:348-350

[60] Schneider S, Eisenhardt D, Rademacher E. Sublethal effects of oxalic acid on *Apis mellifera* (Hymenoptera: Apidae): Changes in behaviour and longevity. Apidologie. 2012;**43**:218-225

**41**

Section 3

Integrated Pest

Management Strategies

Section 3
