Biological and Molecular Effects of Pesticides on Human Health

*Aida Doroudian, Mahdieh Emadi, Reza Hosseinzadeh and Parvaneh Maghami*

## **Abstract**

Pesticides are widely used in agriculture and are practical and economical to improve the quality of food safety for the permanent population around the world. Even though insecticides are beneficial to cropping views, their extensive use may result in severe consequences due to their biocompatible and permanent nature. Various pesticides can cause serious health risks of direct or indirectly contaminated air, water, soil, and the general ecosystem. The effect of pesticides on blood in the mammalian cell is significant because blood can act as a target and carrier for pesticides. However, the mechanism by which they bind to biopolymers, particularly blood proteins, is not clearly understood yet. This chapter investigates the molecular effects of pesticides on biomacromolecules, especially hemoglobin.

**Keywords:** pesticides, hemoglobin, biomolecule

#### **1. Introduction**

Pesticides are an extensive range of materials to destroy, control, and protect plants from any pest, due to the wide range of applications of pesticides in agriculture, industry, and households.

They are the most common chemical that people have a risk of exposure to them. There are two groups of pesticides based on their origins: chemical pesticides and biological pesticides. Chemical pesticides act nonspecific and affect many off-target organisms, while biopesticides operate host-specific. Various pesticides are shown based on their origin or target insect and function [1]. Almost 2 million tons of pesticides are used worldwide each year, overgrowing. Pesticides directly or indirectly contaminate air, water, soil, and entire ecosystems, posing a severe threat to the health of living things [2, 3].

At present, just about 2 million tons of pesticides are used worldwide, and 47.5% belong to herbicides, 29.5% to insecticides, 17.5% to fungicides, and 5.5% to other pesticides [4]. Pesticides can enter the body in different ways, such as through direct contact, digestion, or inhalation. As pesticides enter the body, they enter the blood circulation and the entire body.

Pesticides may enter life forms totally in different ways. Due to contrasts in the digestion system and other characteristics, species, strains, and individuals may significantly

change their defenselessness to pesticides. Oceanic life forms may retain chemicals specifically from the water over respiratory organs (e.g., gills), the body surface, or utilize admissions of sullied nourishment, suspended particles, or sediments [5].

The overall passing and constant illnesses because by pesticide harm number around 1 million every year. The pesticide's high gamble bunches incorporate creation laborers, formulators, sprayers, blenders, loaders, and rural homestead laborers. During production and formulation, the chance of perils might be higher because the cycles implied are not hazard-free. In modern settings, laborers are at expanded hazard since they handle harmful synthetics, including pesticides, poisonous solvents, and inactive transporters [6].

The human well-being impacts of pesticides can happen through one of three courses: ingestion, inward breath, and skin contact that occur through pesticide items. Microorganisms in water and soil are the primary natural system of pesticides debasement. In contrast, the moment is the pesticide's digestion system when living life forms expend it as the portion of their nourishment taken up [7].

The sum of the chance of pesticide introduction depends on the harmfulness and the opening of the pesticide. Harmfulness may be a degree of how destructive or harmful a pesticide is (causing sickness or other undesirable impacts). In contrast, the introduction may be a degree of contact (length) with a pesticide. The poisonous quality is measured as a deadly dosage (LD50). The LD50 esteem is the factual assessment of a pesticide (mg/kg of body weight) that can murder 50% of the test creatures within an expressed period (24 hours to 7 days). The LD50 esteem moreover depends on the course of section of a pesticide; oral LD50 for oral ingestion, dermal LD50 for skin contact introduction, and deadly concentration (LC50) for the inward breath of fumigants and pesticide vapors [8].

Because blood is the body's central circulatory system that can transport a variety of substances to the organs; therefore, it is essential to understand the effects of pesticides on blood and hemoglobin. Investigating the effects of pesticides on biopolymers can help to understand the molecular mechanisms and the hazardous effects of these compounds. Therefore, this chapter aims to study the molecular impact of pesticides.

### **2. Effects of pesticides on cell and metabolism**

Pesticides can affect enzyme actions and metabolic pathways related to the wholecell function (**Figure 1**) [9].

A few pesticides can essentially diminish the action of NADH-dehydrogenase—the fundamental compound of the mitochondrial electron transport chain. The weakness of NADH-dehydrogenase movement by chlorpyrifos might intervene oxidative stress and neurotoxicity. In addition, pesticides can induce the generation of reactive oxygen species (ROS) and receptive nitrogen species (RNS) in cells, which at last prompts oxidative stress and harm to cell structures. Moreover, increased ROS/RNS in vertebrates during digestion and biotransformation of poisonous substances caused hepatotoxicity [9].

Low degrees of pesticides might create an assortment of biochemical changes, some of which might be answerable for the antagonistic organic impacts announced in people and creatures. The harmfulness of pesticides could influence biological organ capacities and biochemical dysfunctions. It was reported a nephrotoxic change in specialists' occupational exposure to pesticides. Changed liver enzymes, like serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST), have been accounted for among pesticide laborers presented to pesticides [10].

*Biological and Molecular Effects of Pesticides on Human Health DOI: http://dx.doi.org/10.5772/intechopen.104811*

**Figure 1.** *Pesticides: Formulates, distribution pathways, and impacts on human well-being [9].*

The interaction between different pesticides may result in numerous responses, depending on contrasts within each compound's chemical properties and modes of poisonous activity. For an improved understanding of the toxic quality of pesticide blends, it is essential to have enough knowledge of the chemical reactivity, the toxicokinetics, metabolic pathways, and the components of activity of each compound. An epidemiological view of physiologically based toxicokinetic and toxicodynamic models, factual modeling, and computational (in silico) toxicology approaches can be used to assess toxicological intelligence [11].

Toxicity effects of pesticides can happen on the activation mechanism of the enzymes at low concentrations; for instance, methyl parathion which is broadly utilized in rural fields, inhibits carbonic anhydrase (CA) and bovine erythrocytes demonstrating that fish in natural and cultural environments are powerless to this pesticide and that methyl parathion pollutions would cause fish and bovine deaths [12].

A few pesticides could regulate the action of efflux carriers or compounds engaged with xenobiotic digestion, prompting an adjustment of the bioavailability and toxicity of other xenobiotics.

Pesticides directly impact a few cell processes and essential proteins engaged with general digestion, cell development, differentiation, and endurance [13].

Moreover, specialists showed a positive connection between openness to pesticides and improvement of certain diseases, especially the brain, prostate, kidney malignant growths, and NHL and leukemia. Some of the examinations on kids observed expanded hazards of illness related to primary times of openness, pre-birth and postpregnancy, and parental openness at work. Many studies showed developed danger and dose-response connections [14].

Different studies show cytotoxicity of the most commonly used pesticides in agriculture on human cell lines. In 2014, Mesnage et al. designed a toxicity test with nine pesticides on three cell lines, including HepG2, HEK293, and JEG3. The results agreed with cytotoxicity after 24 treatments with pesticides by assessing apoptosis and necrosis [15].

Also, similar results were seen by exposing prostate epithelial WPM-Y.1 cell line with imidacloprid and herbicide glyphosate in the study of Abdel-Halim and Osman [16].

Moreover, the study by Abhishek et al. showed the toxicity of parathion methyl (PM) and carbofuran (CN) pesticides on human keratinocyte (HaCaT) cell lines through MTT assay [17].

#### **3. Molecular effects of pesticides**

Besides the effect of pesticides on cells, metabolic systems, and others, still few studies have been done in vitro and in silico analysis that demonstrates these chemical pesticides have a damaging outcome in genetic and epigenetic alterations, specifically on people who are exposed to them by DNA methylation and miRNA expression [18].

DNA methylation status and miRNAs' over-expression are linked to crucial cell and molecular pathways, leading to different human diseases [19].

Genetic susceptibility has accounted for modulating the degree of genotoxic hazard. Many investigations have shown a relationship between DNA harm and glutathione-S-transferase polymorphisms [20].

It was known that oxidative stresses because of ROS created by pesticides disrupt DNA and its repair instrument, prompting transformation and illnesses. DNA fix components help to correct the DNA harm brought about by pesticides. Hard wellbeing impacts because of pesticides range from intense to constant sicknesses, for example, malignant growth, birth absconds, neurological imperfections, reproductive deformities, and immunotoxicity [21].

Oxidative stress is a potential mechanism of toxicity that assumes a critical part in the toxicological pathway of various classes of pesticides, most likely because of their digestion or mitochondrial interruption [22].

#### **3.1 Effects of different pesticides on hemoglobin**

In explaining the destructive effect of pesticides on proteins, extensive experiments have been performed on the interaction of pesticides with hemoglobin as a vital protein.

*Biological and Molecular Effects of Pesticides on Human Health DOI: http://dx.doi.org/10.5772/intechopen.104811*

#### **Figure 2.**

*(a) Ligplot analysis of the interaction between TEPP and hemoglobin [23]. (b) Penetration of TEPP through hydrophobic pocket-3D model [23].*

#### *3.1.1 Interaction of tetraethyl pyrophosphate with hemoglobin*

TEPP1 can dissolve REC and enter red blood cells; also, it can interact with the heme prosthetic group (internal) and induce heme degradation when interacting with Hb.2

LIGPLOT analysis of this interaction (**Figure 2a**) shows that TEPP interacts hydrophobically with aromatic moieties. Docking studies also confirmed the penetration of TEPP into the hydrophobic pocket (**Figure 2b**). The increase in hydrophobicity around aromatic moieties induces a redshift of the globin moiety, as seen in the results of UV-Vis experiments (**Figure 3**).

The blue shift of the Soret (**Figure 4**) band observed is a result of the action of the pesticide on the hydrophobic pocket of Hb. Negative values of Gibbs free energy indicate spontaneous binding of TEPP to Hb. Oxygen affinity measurements and fluorescence studies have shown that this is due to the interaction of TEPP with Hb.

The concentrations of Hb variants (i.e., deoxy-Hb and metHb) increased and [oxyHb] decreased, suggesting that the oxygen transport capacity of Hb was reduced due to the formation of heme degradation products (**Figure 5**). The ATR-FTIR study showed that tetraethyl pyrophosphate could alter the secondary structure of hemoglobin by reducing the alpha-helix content [23].

#### *3.1.2 Interaction of Cartap with hemoglobin*

Carbamate insecticide has a lethal effect on the structure and function of human hemoglobin. As shown in (**Figure 6a**–**c**), changes in Hb absorption were observed in the 200–700 nm range in various concentrations of Cartap.

In addition, the absorption intensity increased at 280 nm, and a bathochromic effect was observed due to the interaction of Cartap and globin through hydrophobic interaction and the change in shape, which was confirmed by molecular docking analysis. In addition, a decrease in the Soret band and Q peak was observed,

<sup>1</sup> Tetraethyl pyrophosphate

<sup>2</sup> Hemoglobin

**Figure 3.** *Red shift in globin region of hemoglobin UV-Vis spectrum due to interaction with TEPP [23].*

**Figure 4.**

*Blue shift in Soret band of hemoglobin UV-Vis spectrum due to interaction with TEPP [23].*

indicating the affinity of hemoglobin for oxygen in the presence of turbulence in the heme medium and Cartap.

This study shows that the Cartap cause loses standard functionality and negatively affects oxygen affinity and transport. Also, based on thermodynamic analysis (**Figure 7**), HB's stability is reduced in the presence of Cartap. According to the

*Biological and Molecular Effects of Pesticides on Human Health DOI: http://dx.doi.org/10.5772/intechopen.104811*

**Figure 5.** *Formation of different hemoglobin variants due to interaction with Hb [23].*

#### **Figure 6.**

*(a) UV-Vis spectral changes and red shift in globin region due to interaction with different concentrations of Cartap hydrochloride with hemoglobin [24]. (b) UV-Vis spectral changes in the Soret region due to interaction with different concentrations of Cartap hydrochloride with hemoglobin [24]. (c) UV-Vis spectral changes and blue shift in Q bands due to interaction with different concentrations of Cartap hydrochloride with hemoglobin [24].*

molecular docking, Hb has two binding sites Cartap hydrochloride (**Figure 8**), and is effectively related to proteins through hydrogen bonding and pocket residual water keys. According to the results, hydrogen bonding and hydrophobic interactions play

**Figure 7.** *Thermal denaturation of hemoglobin upon interaction with different concentrations of Cartap hydrochloride [24].*

**Figure 8.** *Docking 3D model of the interaction between Cartap and hemoglobin [24].*

an essential role in the interaction of Cartap with HB, which can denature protein structures.

These results show that the interaction of Cartap and hemoglobin results in structural and functional changes in hemoglobin and porphyrin [24].
