Trace Elements in Environmental Problems

**79**

**Chapter 6**

**Abstract**

Trace Elements in Urban

Particulate Matters: Variations

*Emmanuel Gbenga Olumayede, B. Babalola and I. Oghenovo*

Trace elements-bound to particulate matters are often become entrained in human respiratory airway, deposited in human nasal cavity and made available for absorption by human tracheobronchial. It has been assumed that variability and bioaccessibility of elements in the serum correlate with some health and diseases. This chapter is a summary of previous works on bioaccessibility of trace elements bound to inhale particulates using different kinds of simulated body fluids. Presented also are evidences of serum variation in some respiratory diseases, such as chronic obstructive pulmonary disease (with or without hypertension), emphysema, bronchiectasis and bronchial asthma, non-tuberculose mycobacterial (NTM)

**Keywords:** trace elements, particulate matters, inhalation bioaccessibility,

tion of PM of ≤10 μm in diameter (PM10) ranges from <10 μg/m3

industries and domestic fuels combustion [2].

Since the industrial revolution, a considerable increase in air pollution has been noted. According to a World Health Organization air quality report [1], inhalation of trace elements bound to airborne particulates is worsening air pollution in cities of the world, thereby causing more than 2 million premature deaths annually. In urban centers, particulate matters are major pollutants in the atmosphere, as they present health risk to dwellers. Urban particulates are known for their heterogeneous mix with diverse natural and anthropogenic origins. The composition can vary depending on geographical location, resuspended soil, atmospheric deposition and sources, which include traffic related particles such as metallic components, eroded road pavement, building construction and demolition, and power generation [2, 3]. The mean daily concentra-

2002 the USEPA reported a range of maximal city concentrations of 25–534 μg/m3

These toxic contaminants originated mainly from the anthropogenic emission sources, through ubiquitous applications of elements in urban centers including automobile,

to 200/m3

[4]. In

[5].

in Serum Levels, Inhalation

Bioaccessibility, Health and

Disease Effects

lung disease, idiopathic pulmonary fibrosis (IPF).

respiratory fluid, health effect, disease

**1. Introduction**

#### **Chapter 6**

## Trace Elements in Urban Particulate Matters: Variations in Serum Levels, Inhalation Bioaccessibility, Health and Disease Effects

*Emmanuel Gbenga Olumayede, B. Babalola and I. Oghenovo*

#### **Abstract**

Trace elements-bound to particulate matters are often become entrained in human respiratory airway, deposited in human nasal cavity and made available for absorption by human tracheobronchial. It has been assumed that variability and bioaccessibility of elements in the serum correlate with some health and diseases. This chapter is a summary of previous works on bioaccessibility of trace elements bound to inhale particulates using different kinds of simulated body fluids. Presented also are evidences of serum variation in some respiratory diseases, such as chronic obstructive pulmonary disease (with or without hypertension), emphysema, bronchiectasis and bronchial asthma, non-tuberculose mycobacterial (NTM) lung disease, idiopathic pulmonary fibrosis (IPF).

**Keywords:** trace elements, particulate matters, inhalation bioaccessibility, respiratory fluid, health effect, disease

#### **1. Introduction**

Since the industrial revolution, a considerable increase in air pollution has been noted. According to a World Health Organization air quality report [1], inhalation of trace elements bound to airborne particulates is worsening air pollution in cities of the world, thereby causing more than 2 million premature deaths annually. In urban centers, particulate matters are major pollutants in the atmosphere, as they present health risk to dwellers. Urban particulates are known for their heterogeneous mix with diverse natural and anthropogenic origins. The composition can vary depending on geographical location, resuspended soil, atmospheric deposition and sources, which include traffic related particles such as metallic components, eroded road pavement, building construction and demolition, and power generation [2, 3]. The mean daily concentration of PM of ≤10 μm in diameter (PM10) ranges from <10 μg/m3 to 200/m3 [4]. In 2002 the USEPA reported a range of maximal city concentrations of 25–534 μg/m3 [5]. These toxic contaminants originated mainly from the anthropogenic emission sources, through ubiquitous applications of elements in urban centers including automobile, industries and domestic fuels combustion [2].

Quite a lot of researchers have investigated elemental compositions of suspended particulate matters in cities worldwide [4–9]. In most of these studies, elevated levels of trace elements have been observed in atmospheric suspended dust in most cities. For example, Okunola *et al.* [8] reported the presence of Cd, Cr, Ni, Pb, Cu, and Zn in atmospheric settling dust in Kano metropolis of Nigeria. Meanwhile, Mafuyai *et al.* [9] reported that the concentrations of some trace elements were found to be far above the standard limits prescribed by WHO for respirable dust in Jos, Nigeria. Therefore, urban dwellers are exposed to considerable amounts of these elements through inhalation of airborne particulates.

Once inhaled, these particles are deposited in the lung and thereby cause serious health effects. Ruby *et al* [10] reported that more than 80% of the binding mass of particles smaller than 2.5 μm reaches the pulmonary alveoli, where a small fraction is deposited and can stay for months to years. Zwozdziak *et al* [11] has also observed that elements deposition in human respiratory tract decreases with increase depth. Recognizing that dissolution of inhaled particulate-bound metal in the body has been observed to depend on the ability of such metal to be solubilized in body fluids [8], therefore it is only such soluble fraction of the elements which can be taken across the cell membrane through lung pathway that have direct effects on health. Hence, it is important to assess the bioaccessibility of trace elements bound to inhale particles over total metal concentration in particle's matrix.

In this chapter, we aimed to discuss the fates, mechanism of toxicity, and recent trends in assessment of bioaccessibility of trace elements. Attempt was made to understand influence of serum levels on trace elements in some respiratory disorders such as chronic obstructive pulmonary disease (COPD), bronchial asthma. This presentation will not consider routes of exposure other than inhalation of particulate matters.

#### **2. Trace elements**

Trace elements are elements present in natural materials at concentration of <1000 mgkg−1 [11]. Some of them are essential micronutrients that exist in very low concentrations in the body, forming 0.01% of the total body weight [12] while others are classified as non-essential. Generally, the major trace elements in atmospheric dust are: iron, manganese, zinc, vanadium, chromium, nickel, copper, cobalt, lead, cadmium, mercury.

#### **2.1 The roles of trace elements in biological processes**

Some trace elements are essential for human body; for cell metabolism regulation, including activation or inhibition of enzymatic reactions, and regulation of gene and membrane functions.

Many enzymes have trace elements within their structures and these trace elements act as a cofactor to them [13]. These enzymes play important roles in protection of the body by their activatory or inhibitory and antioxidant activities, with defense system molecules in diseases. For example, Iron is an important constituent of succinate dehydrogenase as well as part of heme of the haemoglobin, myoglobin and the cytochromes [14]. Zinc is involved in carbonic acid (Carbonic anhydrase) and in alcohol (alcohol dehydrogenase) formation, and in proteolysis (Carboxypeptidase, leucine, aminopeptidase etc) [15]. Copper is present in many enzymes involved in oxidation (tyrosinase, ceuloplasmin, amino oxidase, cytochrome oxidase) [16]. Changes in the levels of these trace elements decrease the

**81**

**Figure 1.**

centers.

observed.

*Trace Elements in Urban Particulate Matters: Variations in Serum Levels, Inhalation...*

with metabolic disturbance, tissue damage and infectious diseases.

efficiency of the antioxidants systems and lead to hyper-reactivity and inflamma-

Although, trace elements play important roles in various physiological processes and are crucial for functioning of the immune system. However, excessive accumulation or deficiency of some of these elements in human body may be associated

**3. Sources of particulate matters and trace elements in urban atmosphere**

Human activities have been found to contribute more to environmental pollution due to the everyday manufacturing of goods to meet the demands of the large population [19]. Particulate matters in the environment emanate from two main sources: (i) Environmental sources: this include processes like forest fires, marine water sprays, and volcanic emissions, and (ii) Human-derived sources include a variety of largely industrial sources, like cement and metals manufacturing, incinerators, power plants, refineries, smelters, and vehicular exhaust and dust. Include volcanic products, minerals which occur naturally in the environment Anthropogenic activities such as Oil, natural gas production, petroleum utilization, combustion products (ie, lead in gasoline), manufacturing/industrial wastes and byproducts; commercial products (ie, lead paint in houses), or spills thereof (ie, commercial chemicals), municipal waste incinerators, landfills, sewage sludge disposal etc. **Figure 1** illustrates the cycle of trace elements in atmosphere of urban

Meanwhile, trace elements in the atmosphere originate mainly from anthropogenic emission sources, through ubiquitous applications of elements in urban centers including automobile, industries and domestic fuels combustion [20]. Trace elements emitted in wind-blown dusts are mostly from industrial areas. Some important anthropogenic sources which significantly contribute to the atmospheric pollution in urban centers include automobile exhaust which releases lead; smelting which releases arsenic, copper and zinc; insecticides which release arsenic and burning of fossil fuels which release nickel, vanadium, mercury, selenium and tin. Other metals reported on the particles are iron (Fe), Zinc (Zn), and Nickel (Ni), and recently with the use of the catalytic converters an increase in the presence of Platinum (Pt), Paladium (Pd) and Rhodium (Rh) in the particles inhaled has been

*Cycling of trace elements in the urban atmosphere. Source: http://doi.org/10.1016/j.scitotenv.2019.13447.*

*DOI: http://dx.doi.org/10.5772/intechopen.96364*

tion in the respiratory tract [17, 18].

*Trace Elements in Urban Particulate Matters: Variations in Serum Levels, Inhalation... DOI: http://dx.doi.org/10.5772/intechopen.96364*

efficiency of the antioxidants systems and lead to hyper-reactivity and inflammation in the respiratory tract [17, 18].

Although, trace elements play important roles in various physiological processes and are crucial for functioning of the immune system. However, excessive accumulation or deficiency of some of these elements in human body may be associated with metabolic disturbance, tissue damage and infectious diseases.

#### **3. Sources of particulate matters and trace elements in urban atmosphere**

Human activities have been found to contribute more to environmental pollution due to the everyday manufacturing of goods to meet the demands of the large population [19]. Particulate matters in the environment emanate from two main sources: (i) Environmental sources: this include processes like forest fires, marine water sprays, and volcanic emissions, and (ii) Human-derived sources include a variety of largely industrial sources, like cement and metals manufacturing, incinerators, power plants, refineries, smelters, and vehicular exhaust and dust. Include volcanic products, minerals which occur naturally in the environment Anthropogenic activities such as Oil, natural gas production, petroleum utilization, combustion products (ie, lead in gasoline), manufacturing/industrial wastes and byproducts; commercial products (ie, lead paint in houses), or spills thereof (ie, commercial chemicals), municipal waste incinerators, landfills, sewage sludge disposal etc. **Figure 1** illustrates the cycle of trace elements in atmosphere of urban centers.

Meanwhile, trace elements in the atmosphere originate mainly from anthropogenic emission sources, through ubiquitous applications of elements in urban centers including automobile, industries and domestic fuels combustion [20]. Trace elements emitted in wind-blown dusts are mostly from industrial areas. Some important anthropogenic sources which significantly contribute to the atmospheric pollution in urban centers include automobile exhaust which releases lead; smelting which releases arsenic, copper and zinc; insecticides which release arsenic and burning of fossil fuels which release nickel, vanadium, mercury, selenium and tin. Other metals reported on the particles are iron (Fe), Zinc (Zn), and Nickel (Ni), and recently with the use of the catalytic converters an increase in the presence of Platinum (Pt), Paladium (Pd) and Rhodium (Rh) in the particles inhaled has been observed.

*Trace Elements and Their Effects on Human Health and Diseases*

Quite a lot of researchers have investigated elemental compositions of suspended particulate matters in cities worldwide [4–9]. In most of these studies, elevated levels of trace elements have been observed in atmospheric suspended dust in most cities. For example, Okunola *et al.* [8] reported the presence of Cd, Cr, Ni, Pb, Cu, and Zn in atmospheric settling dust in Kano metropolis of Nigeria. Meanwhile, Mafuyai *et al.* [9] reported that the concentrations of some trace elements were found to be far above the standard limits prescribed by WHO for respirable dust in Jos, Nigeria. Therefore, urban dwellers are exposed to considerable amounts of these elements through inhalation of airborne particulates.

Once inhaled, these particles are deposited in the lung and thereby cause serious health effects. Ruby *et al* [10] reported that more than 80% of the binding mass of particles smaller than 2.5 μm reaches the pulmonary alveoli, where a small fraction is deposited and can stay for months to years. Zwozdziak *et al* [11] has also observed that elements deposition in human respiratory tract decreases with increase depth. Recognizing that dissolution of inhaled particulate-bound metal in the body has been observed to depend on the ability of such metal to be solubilized in body fluids [8], therefore it is only such soluble fraction of the elements which can be taken across the cell membrane through lung pathway that have direct effects on health. Hence, it is important to assess the bioaccessibility of trace elements bound to

In this chapter, we aimed to discuss the fates, mechanism of toxicity, and recent trends in assessment of bioaccessibility of trace elements. Attempt was made to understand influence of serum levels on trace elements in some respiratory disorders such as chronic obstructive pulmonary disease (COPD), bronchial asthma. This presentation will not consider routes of exposure other than inhalation of

Trace elements are elements present in natural materials at concentration of <1000 mgkg−1 [11]. Some of them are essential micronutrients that exist in very low concentrations in the body, forming 0.01% of the total body weight [12] while others are classified as non-essential. Generally, the major trace elements in atmospheric dust are: iron, manganese, zinc, vanadium, chromium, nickel, copper,

Some trace elements are essential for human body; for cell metabolism regulation, including activation or inhibition of enzymatic reactions, and regulation of

Many enzymes have trace elements within their structures and these trace elements act as a cofactor to them [13]. These enzymes play important roles in protection of the body by their activatory or inhibitory and antioxidant activities, with defense system molecules in diseases. For example, Iron is an important constituent of succinate dehydrogenase as well as part of heme of the haemoglobin, myoglobin and the cytochromes [14]. Zinc is involved in carbonic acid (Carbonic anhydrase) and in alcohol (alcohol dehydrogenase) formation, and in proteolysis (Carboxypeptidase, leucine, aminopeptidase etc) [15]. Copper is present in many enzymes involved in oxidation (tyrosinase, ceuloplasmin, amino oxidase, cytochrome oxidase) [16]. Changes in the levels of these trace elements decrease the

inhale particles over total metal concentration in particle's matrix.

**80**

particulate matters.

**2. Trace elements**

cobalt, lead, cadmium, mercury.

gene and membrane functions.

**2.1 The roles of trace elements in biological processes**

#### **4. Routes of exposure and safety limit of some trace elements**

For a better understanding of the significances of trace element in human health, it is important to have some knowledge of their routes of exposure. Human are exposed to trace elements in the environment through different routes including ingestion, inhalation of dusts, gases, aerosols and dermal absorption (through skin). The main routes of exposure to trace elements bound to particulate matter (PM) in urban centers include occupational exposure through activities listed below for some specific elements such as:

#### **4.1 Cadmium (Cd)**

Cd is an environmentally widespread toxic element. It is classified as a group I carcinogen by IARC (International Agency for Research on Cancer) and has been associated with lung cancer [21]. The modes of human exposure are contamination food, drinking water, occupational or by inhalation in polluted air. Occupational exposure to cadmium primarily takes place in industrial factories such as zinc smelters, battery manufacturing and metal-recovering factories, cadmium-refining companies, production units for paint and pigment. The threshold safety cadmium exposure level has been set at 2.5 μg/kg body weight per week [21]. Cadmium (Cd) exposure is known to induce pulmonary damage such as emphysema and lung cancer [22].

#### **4.2 Lead (Pb)**

Worldwide, lead in atmosphere originates from human activities following its uses as; gasoline additive, paints, cosmetics, ceramic glaze, etc. [23]. Lead enters the human body by ingestion or inhalation. According to the WHO-OSHA, the established safety standard for blood lead in workers is 40 μg/dL. However, it has been suggested that the criterion for elevated blood levels in children is too high in adults therefore recommended a new set of guidelines levels >15 μg/dL [24].

#### **4.3 Manganese (Mn)**

Atmospheric Manganese originated from gasoline additive, methylcyclopentadienyl manganese tricarbonyl (MMT) is a putative modulator of dopamine biology (the primary target of Mn neurotoxicity) [25].

#### **4.4 Chromium (Cr)**

Chromium is widely used in the industry for the production of stainless steel, chromium plating, and spray-painting. According to World Health Organization (WHO) [26], the long term exposure of Cr (VI) levels of over 0.1 ppm causes respiratory problems, liver and kidney damage, and carcinogenicity. According to epidemiological studies, the hexavalent form [Cr (VI)] of this metal, appears to be drastically toxic and carcinogenic, thus it has been classified as carcinogenic to humans by the IARC [27].

#### **4.5 Aluminum (Al)**

Aluminum and its compounds [28] are released into the atmosphere during activities such as aluminum mining, processing, production and recovery. The skin,

**83**

airways [41].

*Trace Elements in Urban Particulate Matters: Variations in Serum Levels, Inhalation...*

nose, lung and gastrointestinal tract is a route for the uptake of aluminum in the body [29]. Therefore, people close to industrial areas may be exposed to aluminum

Elemental arsenic is a metalloid that exists in valency states; trivalent ASIII,

include; occupational, environmental and medicinal sources. The safety level of arsenic has been lowered from 50 ppb to 10 ppb by United State Environmental Protection Agency [30]. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. All the potential pathways of its exposure seem to have adverse effect on human health [31]. Arsenic exposure has been

Vanadium is a major transition element that is released primarily by the burning of fossil fuels, including petroleum, oil, coal, tar, bitumen, and asphaltite. Among Vanadium compounds, Vanadium pentoxide is highly toxic [33]. The IARC classi-

Occupational studies of workers exposed to zinc by inhalation (usually in the presence of other trace elements such as copper, lead, arsenic, and chromium) have

**5. Behavior, fate, and effects of trace elements in the respiratory tract**

The fate and behavior of trace elements in respiratory tract are fundamental to understanding of their health effects and in recent time has become a key aspect of

Particulate matters are inhaled during breathing. Upon inhalation, deposition of the particles in the lung may occur through five different mechanisms: sedimentation (gravity), inertial impaction, interception (particle-surface contact), electrostatic deposition, and diffusion. These mechanisms generally occur in different regions of the respiratory tract [36, 37]. Human respiratory tract can be divided into the upper respiratory region (nasal airway, pharynx and larynx), the lower respiratory region (trachea and bronchi) and the alveolar region. **Figure 2a** shows the particle size distribution in human respiratory tract. Meanwhile **Figure 2(b**) llustrates the health risk of trace elements and bioaccessibility questions. The extent of particle deposition in the lung is determined by the physicochemical properties of the particles, such as size, shape, density, and surface chemistry [38] (see **Figure 2a**). Breathing conditions, like ventilation rate, mouth or nose breathing, and airway geometry are other factors that affect particle deposition [39]. The transportation of particles into the lung can be explained by their aerodynamic diameter [40]. Meanwhile, materials with an aerodynamic diameter below 5 μm are predominantly deposited in the alveolar regions of the

in the environment. The main sources of exposure to arsenic

*DOI: http://dx.doi.org/10.5772/intechopen.96364*

through inhalation of airborne particulates.

repeatedly associated with lung carcinogenesis [32].

not implicated zinc as a risk factor for cancer [35].

**5.1 The respiratory tract and deposition of PM in the lung**

potential health risk assessment.

fied it as a possible carcinogen to humans (Group 2B) in 2003 [34].

**4.6 Arsenic (As)**

pentavalent As<sup>v</sup>

**4.7 Vanadium**

**4.8 Zinc**

*Trace Elements in Urban Particulate Matters: Variations in Serum Levels, Inhalation... DOI: http://dx.doi.org/10.5772/intechopen.96364*

nose, lung and gastrointestinal tract is a route for the uptake of aluminum in the body [29]. Therefore, people close to industrial areas may be exposed to aluminum through inhalation of airborne particulates.

#### **4.6 Arsenic (As)**

*Trace Elements and Their Effects on Human Health and Diseases*

for some specific elements such as:

**4.1 Cadmium (Cd)**

cancer [22].

**4.2 Lead (Pb)**

levels >15 μg/dL [24].

**4.3 Manganese (Mn)**

**4.4 Chromium (Cr)**

**4.5 Aluminum (Al)**

(the primary target of Mn neurotoxicity) [25].

**4. Routes of exposure and safety limit of some trace elements**

For a better understanding of the significances of trace element in human health, it is important to have some knowledge of their routes of exposure. Human are exposed to trace elements in the environment through different routes including ingestion, inhalation of dusts, gases, aerosols and dermal absorption (through skin). The main routes of exposure to trace elements bound to particulate matter (PM) in urban centers include occupational exposure through activities listed below

Cd is an environmentally widespread toxic element. It is classified as a group I carcinogen by IARC (International Agency for Research on Cancer) and has been associated with lung cancer [21]. The modes of human exposure are contamination food, drinking water, occupational or by inhalation in polluted air. Occupational exposure to cadmium primarily takes place in industrial factories such as zinc smelters, battery manufacturing and metal-recovering factories, cadmium-refining companies, production units for paint and pigment. The threshold safety cadmium exposure level has been set at 2.5 μg/kg body weight per week [21]. Cadmium (Cd) exposure is known to induce pulmonary damage such as emphysema and lung

Worldwide, lead in atmosphere originates from human activities following its uses as; gasoline additive, paints, cosmetics, ceramic glaze, etc. [23]. Lead enters the human body by ingestion or inhalation. According to the WHO-OSHA, the established safety standard for blood lead in workers is 40 μg/dL. However, it has been suggested that the criterion for elevated blood levels in children is too high in adults therefore recommended a new set of guidelines

Atmospheric Manganese originated from gasoline additive, methylcyclopentadienyl manganese tricarbonyl (MMT) is a putative modulator of dopamine biology

Chromium is widely used in the industry for the production of stainless steel, chromium plating, and spray-painting. According to World Health Organization (WHO) [26], the long term exposure of Cr (VI) levels of over 0.1 ppm causes respiratory problems, liver and kidney damage, and carcinogenicity. According to epidemiological studies, the hexavalent form [Cr (VI)] of this metal, appears to be drastically toxic and carcinogenic, thus it has been classified as carcinogenic to humans by the

Aluminum and its compounds [28] are released into the atmosphere during activities such as aluminum mining, processing, production and recovery. The skin,

**82**

IARC [27].

Elemental arsenic is a metalloid that exists in valency states; trivalent ASIII, pentavalent As<sup>v</sup> in the environment. The main sources of exposure to arsenic include; occupational, environmental and medicinal sources. The safety level of arsenic has been lowered from 50 ppb to 10 ppb by United State Environmental Protection Agency [30]. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. All the potential pathways of its exposure seem to have adverse effect on human health [31]. Arsenic exposure has been repeatedly associated with lung carcinogenesis [32].

#### **4.7 Vanadium**

Vanadium is a major transition element that is released primarily by the burning of fossil fuels, including petroleum, oil, coal, tar, bitumen, and asphaltite. Among Vanadium compounds, Vanadium pentoxide is highly toxic [33]. The IARC classified it as a possible carcinogen to humans (Group 2B) in 2003 [34].

#### **4.8 Zinc**

Occupational studies of workers exposed to zinc by inhalation (usually in the presence of other trace elements such as copper, lead, arsenic, and chromium) have not implicated zinc as a risk factor for cancer [35].

#### **5. Behavior, fate, and effects of trace elements in the respiratory tract**

The fate and behavior of trace elements in respiratory tract are fundamental to understanding of their health effects and in recent time has become a key aspect of potential health risk assessment.

#### **5.1 The respiratory tract and deposition of PM in the lung**

Particulate matters are inhaled during breathing. Upon inhalation, deposition of the particles in the lung may occur through five different mechanisms: sedimentation (gravity), inertial impaction, interception (particle-surface contact), electrostatic deposition, and diffusion. These mechanisms generally occur in different regions of the respiratory tract [36, 37]. Human respiratory tract can be divided into the upper respiratory region (nasal airway, pharynx and larynx), the lower respiratory region (trachea and bronchi) and the alveolar region. **Figure 2a** shows the particle size distribution in human respiratory tract. Meanwhile **Figure 2(b**) llustrates the health risk of trace elements and bioaccessibility questions. The extent of particle deposition in the lung is determined by the physicochemical properties of the particles, such as size, shape, density, and surface chemistry [38] (see **Figure 2a**). Breathing conditions, like ventilation rate, mouth or nose breathing, and airway geometry are other factors that affect particle deposition [39]. The transportation of particles into the lung can be explained by their aerodynamic diameter [40]. Meanwhile, materials with an aerodynamic diameter below 5 μm are predominantly deposited in the alveolar regions of the airways [41].

**Figure 2.**

*(a) Dust particle sizes distribution in human respiratory tract (b) human health risk and bioaccessibility questions.*

**Figure 3.** *Glutathione-trace element complex.*

When trace elements are absorbed through respiratory tract, it is transported in blood bound to metallothionen [42]. **Figure 3** shows an example of such complex, where they form complex with glutathione. This is then followed by alteration of homeostasis [43], thus directly increasing the oxidative stress and lipid peroxidation.

#### **5.2 Mechanisms of inhaled trace elements toxicity**

A primary mechanism for most trace elements toxicity is their effects on cells which has been ascribed to the oxidative stress promoting actions, as observed in *in vivo* [44] and most importantly, the inactivation of enzyme systems by binding to sulfhydryl groups [45] of proteins. The mechanisms of their actions include genetic change reactions; reactive oxygen free radicals and adduct formations, oxidative stress, and inflammation [46].

#### *5.2.1 Reactive oxygen species (ROS) generation*

Reactive oxygen species (ROS) such as superoxide, hydroxyl radical, nitric oxide radical are byproducts of metabolic processes. External substances such as smoke,

**85**

*Trace Elements in Urban Particulate Matters: Variations in Serum Levels, Inhalation...*

cigerate, pesticides and inhalation of trace elements -bound particulate matters can also cause the formation of free radicals in the body. Trace elements in particulate matters have been reported to cause oxidative stress. For example, pentavalent form of vanadium is reported to cause ROS generation, thus induce oxidative stress, DNA damage, and activation of hypoxia signaling [47]. Oxidation stress is a phenomenon caused by an imbalance between production and accumulation of oxygen reactive species in cell and tissues and the ability of a biological system to detoxify these reactive products [48]. Cadmium causes liver damage mainly by induction ROS inducing lipoperoxidation via Fenton reaction [49]. The increment of ROS induces DNA damage, proteins oxidation and lipid peroxidation. Copper ions are well suited to facilitate formation of ROS that can damage biomolecules, including DNA and chromatin.

The genetic changes reaction of trace elements involves: formation of DNA-protein cross-links, single and double strand DNA breaks [49, 50]. The reaction of elemental ions with nucleic acid lead to a variety of dramatic effects on the nucleic acid structure e.g. crosslinking of polymer strands, degradation to oligomer and monomers, stabilization or destabilization, and the mispairing of bases. For example, Copper can directly bind with high affinity to DNA molecule; this binding can modify the conformational structure of DNA promoting carcinogenesis [51]. Cadmium also produces genotoxicity by the production of DNA single strand breaks and damage and competes for binding at sites (specifically with a zinc finger motifs that are important in gene regulation, enzyme activity, or maintenance of genomic stability [52]).

In toxicological study, the potential health risks of individual elements bound to inhale particulate matter depend on particle size, inhalability, bioavailability/ bioaccessibility, exposure dose and deposition/retention in respiratory tract [53, 54]. Recently, it was emphasized that bio-toxicities of trace metals depend not only on the concentration as expressed by total amount, but also on their geochemical fractions and bioavailability [55]. Bioavailability is the fraction of total elements that can enter the human systemic circulation and exert toxicity on the organs [56]. Meanwhile, bioaccessibility refers to the fraction of contaminant that may become available for absorption *e.g.*, solubilized in the respiratory tract fluid or volatilized into inhaled air and released from the matrix in a topically absorbable form. Bioaccessibility (%) can be defined as the ratio of soluble fraction of trace elements in simulated lung fluids

The dissolution of particulate-bound metal in the body has been observed to depend on the ability of such element to be bioaccessible (solubilized) in body fluids after inhalation [57]. Different particulate-bound elemental species behaves differently in human body after inhalation and deposition, depending on their bioaccessibility in lung fluids. In general, high bioaccessible elements are easily taken up by the lung fluids and get introduced to human circulatory system. Recognizing that only soluble fraction of the metals which can be taken across the cell membrane through lung pathway has more direct effects on health. Thus, bioaccessibility of trace elements bound to inhale particles over total metal concentration in particle's matrix is being considered important for assessment of the overall health risk

*DOI: http://dx.doi.org/10.5772/intechopen.96364*

*5.2.2 DNA adducts formation*

(SLF) to the total concentrations.

**5.3 Concept of bioavailability and bioaccessibility**

*5.3.1 Bioaccessibility of trace elements bound to particulate matter*

associated with inhalation of particulate matters.

*Trace Elements in Urban Particulate Matters: Variations in Serum Levels, Inhalation... DOI: http://dx.doi.org/10.5772/intechopen.96364*

cigerate, pesticides and inhalation of trace elements -bound particulate matters can also cause the formation of free radicals in the body. Trace elements in particulate matters have been reported to cause oxidative stress. For example, pentavalent form of vanadium is reported to cause ROS generation, thus induce oxidative stress, DNA damage, and activation of hypoxia signaling [47]. Oxidation stress is a phenomenon caused by an imbalance between production and accumulation of oxygen reactive species in cell and tissues and the ability of a biological system to detoxify these reactive products [48]. Cadmium causes liver damage mainly by induction ROS inducing lipoperoxidation via Fenton reaction [49]. The increment of ROS induces DNA damage, proteins oxidation and lipid peroxidation. Copper ions are well suited to facilitate formation of ROS that can damage biomolecules, including DNA and chromatin.

#### *5.2.2 DNA adducts formation*

*Trace Elements and Their Effects on Human Health and Diseases*

When trace elements are absorbed through respiratory tract, it is transported in blood bound to metallothionen [42]. **Figure 3** shows an example of such complex, where they form complex with glutathione. This is then followed by alteration of homeostasis [43], thus directly increasing the oxidative stress and lipid

*(a) Dust particle sizes distribution in human respiratory tract (b) human health risk and bioaccessibility* 

A primary mechanism for most trace elements toxicity is their effects on cells which has been ascribed to the oxidative stress promoting actions, as observed in *in vivo* [44] and most importantly, the inactivation of enzyme systems by binding to sulfhydryl groups [45] of proteins. The mechanisms of their actions include genetic change reactions; reactive oxygen free radicals and adduct formations, oxidative

Reactive oxygen species (ROS) such as superoxide, hydroxyl radical, nitric oxide radical are byproducts of metabolic processes. External substances such as smoke,

**5.2 Mechanisms of inhaled trace elements toxicity**

**84**

peroxidation.

*Glutathione-trace element complex.*

**Figure 3.**

**Figure 2.**

*questions.*

stress, and inflammation [46].

*5.2.1 Reactive oxygen species (ROS) generation*

The genetic changes reaction of trace elements involves: formation of DNA-protein cross-links, single and double strand DNA breaks [49, 50]. The reaction of elemental ions with nucleic acid lead to a variety of dramatic effects on the nucleic acid structure e.g. crosslinking of polymer strands, degradation to oligomer and monomers, stabilization or destabilization, and the mispairing of bases. For example, Copper can directly bind with high affinity to DNA molecule; this binding can modify the conformational structure of DNA promoting carcinogenesis [51]. Cadmium also produces genotoxicity by the production of DNA single strand breaks and damage and competes for binding at sites (specifically with a zinc finger motifs that are important in gene regulation, enzyme activity, or maintenance of genomic stability [52]).

#### **5.3 Concept of bioavailability and bioaccessibility**

In toxicological study, the potential health risks of individual elements bound to inhale particulate matter depend on particle size, inhalability, bioavailability/ bioaccessibility, exposure dose and deposition/retention in respiratory tract [53, 54]. Recently, it was emphasized that bio-toxicities of trace metals depend not only on the concentration as expressed by total amount, but also on their geochemical fractions and bioavailability [55]. Bioavailability is the fraction of total elements that can enter the human systemic circulation and exert toxicity on the organs [56]. Meanwhile, bioaccessibility refers to the fraction of contaminant that may become available for absorption *e.g.*, solubilized in the respiratory tract fluid or volatilized into inhaled air and released from the matrix in a topically absorbable form. Bioaccessibility (%) can be defined as the ratio of soluble fraction of trace elements in simulated lung fluids (SLF) to the total concentrations.

#### *5.3.1 Bioaccessibility of trace elements bound to particulate matter*

The dissolution of particulate-bound metal in the body has been observed to depend on the ability of such element to be bioaccessible (solubilized) in body fluids after inhalation [57]. Different particulate-bound elemental species behaves differently in human body after inhalation and deposition, depending on their bioaccessibility in lung fluids. In general, high bioaccessible elements are easily taken up by the lung fluids and get introduced to human circulatory system. Recognizing that only soluble fraction of the metals which can be taken across the cell membrane through lung pathway has more direct effects on health. Thus, bioaccessibility of trace elements bound to inhale particles over total metal concentration in particle's matrix is being considered important for assessment of the overall health risk associated with inhalation of particulate matters.


*Trace Elements and Their Effects on Human Health and Diseases*

**Table 1.**

**87**

**6.2 Bronchial asthma**

*Trace Elements in Urban Particulate Matters: Variations in Serum Levels, Inhalation...*

fluids (SALF), which is simply a modification of Gamble's solution.

Emerging studies [58–60] have shown risk assessment using bioaccessibility presents better understanding of the fate of trace elements upon inhalation by children and adults. However, one of the challenges for environmental toxicologist has been development of fluid with properties similar to human tracheobronchial fluids, so as to enable systematic investigation into bioaccessibility and lung deposition of particles in respiratory tracts [61]. Several fluids have been explored to mimic human respiratory tract fluids in investigation of trace elements bioaccessibility. These range from the traditional Gamble's solution to simulated artificial lung

In one of such previous study, [62] reported that pulmonary bioaccessible fraction of Pb and Cd were relatively high (69 and 74% respectively) when lung stimulating solution (artificial lysosome fluid, ALF) was used to extract fine particles. Similarly, [63–67] reported higher bioaccessibility for Cd (88 ± 6.4% for PM10 and 91 ± 6.6% for PM2.5) when ALF was used as extraction fluid compared to Gamble's solution. Tang *et al* [64] reported that As, Pb, V and Mn showed higher inhalation bioaccessibility extracted by the artificial lysosomal fluid (ALF); while V, As, Sr. and Cd showed higher inhalation bioaccessibility using the simulated lung fluid (SLF), suggesting differences in elemental inhalation bioaccessibility between ALF and SLF extraction. **Table 1** presents the bioaccessibility values of trace elements in the three lung fluids in different reference materials, as reported by [62]. In general, one of the important factors affecting bioaccessibility of trace elements is the influence of fluid's composition and pH.

**6. Variation in serum trace elements levels and induced respiratory tract** 

Inhalation exposure to trace elements can have significant health impacts on urban dwellers and nearby workers. Unlike other organs, lungs are directly and continuously exposed to high oxygen concentrations, exogenous oxidants, and pollutants: thus, they have the greatest susceptibility to oxidative stress and pollutant toxicity. The existence of concentration gradient within the lung and inter-individual concentration differences reveals the existence of two groups of elements: (i) homogeneously distributed over the lung e.g. elements Br, Cs, Cu, K, Na, Rb, Se and Zn, and (ii) heterogeneously

The enrichment of trace elements in the lung tissue is known to result a number of lung diseases. These diseases have been associated with disturbance of trace elements balance [69]. Here, we discussed recent observations on variation of serum levels in diseases such as chronic obstructive pulmonary disease (with or without hypertension), emphysema, bronchiectasis and bronchial asthma, non-tuberculose

distributed e.g. elements such as Cd, Co, Cr, Pb, Sb, Sc and V [68].

**6.1 Chronic obstructive pulmonary disease (COPD)**

mycobacterial (NTM) lung disease, idiopathic pulmonary fibrosis (IPF).

serum copper (Cu) in COPD patients were higher than the control group.

Many trace elements have activator or inhibitory roles in the antioxidants defensive mechanism in diseases. Recent study [70] showed that serum levels of Co, Cu and Fe were higher in COPD patients with pulmonary hypertension compared to COPD patients without pulmonary hypertension. Similarly, [70] reported that the

Bronchial asthma is a chronic inflammatory disease of the respiratory tract with an unknown etiology where inflammation is often associated with an increase

*DOI: http://dx.doi.org/10.5772/intechopen.96364*

**diseases and health problems**

 *Bioaccessibility (%; mean ± SD; n = 3) values of trace elements in the three lung fluids (adopted from [62]).* *Trace Elements in Urban Particulate Matters: Variations in Serum Levels, Inhalation... DOI: http://dx.doi.org/10.5772/intechopen.96364*

Emerging studies [58–60] have shown risk assessment using bioaccessibility presents better understanding of the fate of trace elements upon inhalation by children and adults. However, one of the challenges for environmental toxicologist has been development of fluid with properties similar to human tracheobronchial fluids, so as to enable systematic investigation into bioaccessibility and lung deposition of particles in respiratory tracts [61]. Several fluids have been explored to mimic human respiratory tract fluids in investigation of trace elements bioaccessibility. These range from the traditional Gamble's solution to simulated artificial lung fluids (SALF), which is simply a modification of Gamble's solution.

In one of such previous study, [62] reported that pulmonary bioaccessible fraction of Pb and Cd were relatively high (69 and 74% respectively) when lung stimulating solution (artificial lysosome fluid, ALF) was used to extract fine particles. Similarly, [63–67] reported higher bioaccessibility for Cd (88 ± 6.4% for PM10 and 91 ± 6.6% for PM2.5) when ALF was used as extraction fluid compared to Gamble's solution. Tang *et al* [64] reported that As, Pb, V and Mn showed higher inhalation bioaccessibility extracted by the artificial lysosomal fluid (ALF); while V, As, Sr. and Cd showed higher inhalation bioaccessibility using the simulated lung fluid (SLF), suggesting differences in elemental inhalation bioaccessibility between ALF and SLF extraction. **Table 1** presents the bioaccessibility values of trace elements in the three lung fluids in different reference materials, as reported by [62]. In general, one of the important factors affecting bioaccessibility of trace elements is the influence of fluid's composition and pH.

#### **6. Variation in serum trace elements levels and induced respiratory tract diseases and health problems**

Inhalation exposure to trace elements can have significant health impacts on urban dwellers and nearby workers. Unlike other organs, lungs are directly and continuously exposed to high oxygen concentrations, exogenous oxidants, and pollutants: thus, they have the greatest susceptibility to oxidative stress and pollutant toxicity. The existence of concentration gradient within the lung and inter-individual concentration differences reveals the existence of two groups of elements: (i) homogeneously distributed over the lung e.g. elements Br, Cs, Cu, K, Na, Rb, Se and Zn, and (ii) heterogeneously distributed e.g. elements such as Cd, Co, Cr, Pb, Sb, Sc and V [68].

The enrichment of trace elements in the lung tissue is known to result a number of lung diseases. These diseases have been associated with disturbance of trace elements balance [69]. Here, we discussed recent observations on variation of serum levels in diseases such as chronic obstructive pulmonary disease (with or without hypertension), emphysema, bronchiectasis and bronchial asthma, non-tuberculose mycobacterial (NTM) lung disease, idiopathic pulmonary fibrosis (IPF).

#### **6.1 Chronic obstructive pulmonary disease (COPD)**

Many trace elements have activator or inhibitory roles in the antioxidants defensive mechanism in diseases. Recent study [70] showed that serum levels of Co, Cu and Fe were higher in COPD patients with pulmonary hypertension compared to COPD patients without pulmonary hypertension. Similarly, [70] reported that the serum copper (Cu) in COPD patients were higher than the control group.

#### **6.2 Bronchial asthma**

Bronchial asthma is a chronic inflammatory disease of the respiratory tract with an unknown etiology where inflammation is often associated with an increase

*Trace Elements and Their Effects on Human Health and Diseases*

**86**

**Lung Fluids** **Cd** <LD <LD 81.4 ± 7.6

PBS Gamble's

ALF PBS Gamble's

ALF PBS Gamble's

ALF *LD, Limit of detection.*

**Table 1.**

*Bioaccessibility (%; mean ± SD; n = 3) values of trace elements in the three lung fluids (adopted from [62]).*

24.1 ± 6.2 45.2 ± 4.0 65.6 ± 5.5

1.3 ± 0.4 2.7 ± 1.0 8.7 ± 0.9

55.0 ± 1.1

49.9 ± 2.7

7.3 ± 1.8

44.2 ± 21.2

86.0 ± 2.8 85.3 ± 8.4

7.8 ± 0.0

<LD <LD

59.7 ± 1.4

8.3 ± 0.2 47.6 ± 1.4

28.7 ± 0.4 40.1 ± 0.7 44.3 ± 0.2 **NIST 1648**

16.4 ± 1.4 29.6 ± 0.2 46.8 ± 2.6

<LD 3.3 ± 1.2 12.2 ± 4.1

<LD 9.1 ± 0.9 75.9 ± 2.2

4.3 ± 0.2

43.2 ± 0.2

66.2 ± 2.3

<LD <LD <LD

0.04 ± 0.00

7.8 ± 0.4 55.0 ± 0.5

6.2 ± 0.1

23.7 ± 0.1

35.3 ± 0.1

**Cr** 0.8 ± 0.5 0.5 ± 0.3 8.7 ± 0.0

4.1 ± 1.5 49.9 ± 5.6 65.2 ± 3.7

**Cu**

**BCR-723**

**Trace Element**

**Mn** 0.9 ± 0.0 1.7 ± 0.0 5.5 ± 0.1 **NIST2710**

**Ni** <LD 0.8 ± 0.0 24.1 ± 3.7

**Pb** <LD 7.8 ± 0.6 62.0 ± 3.2

**Zn**

6.8 ± 0.8

44.6 ± 0.8

76.8 ± 2.2

generation of ROS [71]. Several trace elements are known to be capable of causing bronchial asthma, such as nickel (Ni), Chromium (Cr), Cobalt (Co) etc. **Table 2** presents the variations in concentrations of some trace elements (Zn, Cu and Se) in serum of asthmatic, as observed in a study [66]. The results showed higher Cu concentration, and Cu/Zn and lower Cu/Se ratios.

#### **6.3 Idiopathic pulmonary fibrosis (IPF)**

Idiopathic pulmonary fibrosis is an interstitial lung disease with poor prognosis and an undefined etiopathogenesis [72] leading rapidly to death. It is the most common lung disease with estimated incidence of 2.8–9.3% per 100,000 per year in Europe and America [73]. Particulate matters bound trace elements deposited in the lung may give rise to more or less marked pulmonary fibrosis, depending on intrinsic properties and amount of the particulate matters. Oxidative stress by trace elements contributes to alveolar injury and fibrosis development in patients. A study [74] reported that IPF patients had significantly increased sputum levels of Cd, Cr, Cu and Pb respect to control. **Table 3** presents the variations in concentrations of some trace elements in serum in patents with NTM, TB and healthy as control, as reported by [74].


**Table 2.**

*Variation of trace elements in serum of asthmatic patients [66, 67].*


#### **Table 3.**

*Serum levels of trace elements in patents with NTM, TB and healthy [75].*


**89**

*Trace Elements in Urban Particulate Matters: Variations in Serum Levels, Inhalation...*

Non-tuberculose mycobacterial lung diseases are emerging cause of pulmonary infection and are becoming more common in the clinical setting. A recent study [75] showed that serum concentration of copper and molybdenium (**Table 4**) were higher in patients with NTM lung disease (109 vs. 91 μg/dL, p < 0.001 and 1.70 vs. 0.96 μg/L, p < 0.001). In contrast, the media serum concentrations of Selenium and Zinc were significantly lower in patients with non-tuberculose mycobacterial lung diseases than in healthy control (105 vs. 115 μg/L, p < 0.001 and 94 vs. 102 μg/dL,

Oxidants-antioxidants balance is essential for the normal lung function. Both,

Parkinson disease, also known as manganism is an extrapyramidal neurological disease characterized by rigidity action tremor, bradykinesia, memory and cognitive dysfunction that occurs in workers exposed to airborne Mn. The element (Mn) in blood crosses the blood brain barrier and accumulates inside the neuron disrupt-

Trace elements bound to particulate matter could be trapped and deposited along the nasal cavity through inhalation of air-borne particulate matter. In this chapter, we attempted to understand influence of serum levels and bioaccessibility of trace elements in some respiratory fluids. Our investigation provides evidence that enrichment of trace elements in the lung tissue is known to result a number of lung diseases, such as chronic obstructive pulmonary disease (with or without hypertension), bronchial asthma, non-tuberculose mycobacterial (NTM) lung disease, and idiopathic pulmonary fibrosis (IPF). The findings suggest that serum Cu were higher in asthmatic patients and COPD patients than the healthy. Meanwhile, the levels of Se, Zn and Mn were lower in hemodialysis patients and

an increased oxidant and/or decrease antioxidant may reverse the physiologic oxidants-antioxidants balance, leading to lung injury. Available data (**Table 4**) suggested that the levels of Cd, Cr, Pb, and V were higher and the levels of Se, Zn and

Mn were lower in hemodialysis patients compare with controls [76].

ing the synaptic transmission and inducing glial activation [77].

non-tuberculose mycobacterial lung diseases than in healthy control.

**6.4 Non-tuberculose mycobacterial lung diseases (NTM)**

*DOI: http://dx.doi.org/10.5772/intechopen.96364*

p < 0.001).

**6.5 Haemodialysis**

**6.6 Parkinson disease**

**7. Conclusion**

#### **Table 4.**

*Serum levels of trace elements in patents with Haemodialysis compare with control [76].*

*Trace Elements in Urban Particulate Matters: Variations in Serum Levels, Inhalation... DOI: http://dx.doi.org/10.5772/intechopen.96364*

#### **6.4 Non-tuberculose mycobacterial lung diseases (NTM)**

Non-tuberculose mycobacterial lung diseases are emerging cause of pulmonary infection and are becoming more common in the clinical setting. A recent study [75] showed that serum concentration of copper and molybdenium (**Table 4**) were higher in patients with NTM lung disease (109 vs. 91 μg/dL, p < 0.001 and 1.70 vs. 0.96 μg/L, p < 0.001). In contrast, the media serum concentrations of Selenium and Zinc were significantly lower in patients with non-tuberculose mycobacterial lung diseases than in healthy control (105 vs. 115 μg/L, p < 0.001 and 94 vs. 102 μg/dL, p < 0.001).

#### **6.5 Haemodialysis**

*Trace Elements and Their Effects on Human Health and Diseases*

concentration, and Cu/Zn and lower Cu/Se ratios.

**6.3 Idiopathic pulmonary fibrosis (IPF)**

control, as reported by [74].

generation of ROS [71]. Several trace elements are known to be capable of causing bronchial asthma, such as nickel (Ni), Chromium (Cr), Cobalt (Co) etc. **Table 2** presents the variations in concentrations of some trace elements (Zn, Cu and Se) in serum of asthmatic, as observed in a study [66]. The results showed higher Cu

Idiopathic pulmonary fibrosis is an interstitial lung disease with poor prognosis

**Element (**μ**g/L) Patients with NTM (n = 95) Patient with TB (n = 97) Healthy control (n = 99)** Co (μg/L) 0.24(0.20–0.35) 0.54(0.22–0.83) 0.23(0.19–0.27) Cu (μg/L) 109(97–134) 129(111–153) 91(82–102) Cr (μg/L) 0.23(0.19–0.27) 0.23(0.18–0.27) 0.23(0.19–0.28) Mn (μg/L) 0.90(0.81–1.07) 0.93(0.71–1.31) 0.92(0.80–1.23) Se (μg/L) 105(95–116) 108(99–119) 115(105–123) Zn (μg/L) 94(84–107) 84(75–93) 102(92–116)

**Element (**μ**g/mL) Patient Control** Cd (μg/mL) 110 54 Cu (μg/mL) 330 635 Pb (μg/mL) 1217 1444 Mn (μg/mL) 399 522 Se (μg/mL) 1496 1443 Zn (μg/mL) 2515 2699

*Serum levels of trace elements in patents with Haemodialysis compare with control [76].*

*Serum levels of trace elements in patents with NTM, TB and healthy [75].*

*Variation of trace elements in serum of asthmatic patients [66, 67].*

and an undefined etiopathogenesis [72] leading rapidly to death. It is the most common lung disease with estimated incidence of 2.8–9.3% per 100,000 per year in Europe and America [73]. Particulate matters bound trace elements deposited in the lung may give rise to more or less marked pulmonary fibrosis, depending on intrinsic properties and amount of the particulate matters. Oxidative stress by trace elements contributes to alveolar injury and fibrosis development in patients. A study [74] reported that IPF patients had significantly increased sputum levels of Cd, Cr, Cu and Pb respect to control. **Table 3** presents the variations in concentrations of some trace elements in serum in patents with NTM, TB and healthy as

**Mean ± SD Control (n = 25) Patient** Zn (μg/mL) 0.83 (0.14) 0.68(0.09) Cu (μg/mL) 0.76(0.17) 1.10(0.28) Se (μg/mL) 0.116 (0.022) 0.0057 (0.024)

**88**

**Table 4.**

**Table 3.**

**Table 2.**

Oxidants-antioxidants balance is essential for the normal lung function. Both, an increased oxidant and/or decrease antioxidant may reverse the physiologic oxidants-antioxidants balance, leading to lung injury. Available data (**Table 4**) suggested that the levels of Cd, Cr, Pb, and V were higher and the levels of Se, Zn and Mn were lower in hemodialysis patients compare with controls [76].

#### **6.6 Parkinson disease**

Parkinson disease, also known as manganism is an extrapyramidal neurological disease characterized by rigidity action tremor, bradykinesia, memory and cognitive dysfunction that occurs in workers exposed to airborne Mn. The element (Mn) in blood crosses the blood brain barrier and accumulates inside the neuron disrupting the synaptic transmission and inducing glial activation [77].

#### **7. Conclusion**

Trace elements bound to particulate matter could be trapped and deposited along the nasal cavity through inhalation of air-borne particulate matter. In this chapter, we attempted to understand influence of serum levels and bioaccessibility of trace elements in some respiratory fluids. Our investigation provides evidence that enrichment of trace elements in the lung tissue is known to result a number of lung diseases, such as chronic obstructive pulmonary disease (with or without hypertension), bronchial asthma, non-tuberculose mycobacterial (NTM) lung disease, and idiopathic pulmonary fibrosis (IPF). The findings suggest that serum Cu were higher in asthmatic patients and COPD patients than the healthy. Meanwhile, the levels of Se, Zn and Mn were lower in hemodialysis patients and non-tuberculose mycobacterial lung diseases than in healthy control.

*Trace Elements and Their Effects on Human Health and Diseases*

#### **Author details**

Emmanuel Gbenga Olumayede\*, B. Babalola and I. Oghenovo Department of Industrial Chemistry, Federal University Oye-Ekiti, Ekiti State, Nigeria

\*Address all correspondence to: emmanuel.olumayede@fuoye.edu.ng

© 2021 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.

**91**

*Trace Elements in Urban Particulate Matters: Variations in Serum Levels, Inhalation...*

Atmospheric Settling Dust along Roads in Kano Metropolis, Nigeria. Journal of Applied Chem., 2015, Article ID

[10] Mafuyai GM, Eneji IS, Sha'Ato R. Concentration of Heavy Metals in respiratory Dust in Jos Metropolitan Area, Nigeria. Open Journal of Air Pollution, 2014; 3: 10-19 http://dx.doi.

[11] Ruby MV, Lowney YW, Bunge AL, Roberts SM, Gomez-Eyles JL, Ghosh U, Kissel JC, Tomlin-son P, Menzie C. Oral Bioavailability, Solubility or dissolution, and Dermal Absorption of PAHs from Soil-State of the Science. Environ. Sci.

org/10.4236/ajop.2014.31002.

Technol., 2016; 50: 2151-2164

[13] Foster WM, Langenback E,

Physiol., 1980; 48: 965-971.

retention model accounting for dissolution and macrophage-mediated removal of deposited polydisperse particles, Inhal. Toxicol., 2001; 13:

Bergofsky EH. Measurement of tracheal and bronchial mucus velocities in man: relation to lung clearance. J Appl

[14] Stöber WKW. A simple pulmonary

[15] Sharareh Dehghani. Farid Moore. Luba Vasiluk. Beverley A. Hale The influence of physicochemical parameters on bioaccessibility-adjusted hazard quotients for copper, lead and zinc in different grain size fractions of urban street dusts and soils. Environ

103: 38-52

129-148.

[12] Zwozdzaik A, Gini MI, Samek L, Rogula-Kozlowka W, Sowka L, Eleftheriadis K. Implications of the aerosols size distribution modal structure of trace and major elements on human exposure, inhaled dose and relevance to the PM2.5 and PM10 metrics in European pollution hotspot urban area. J. Aerosol Science. 2017;

739325, 12Pages

*DOI: http://dx.doi.org/10.5772/intechopen.96364*

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**Author details**

Ekiti State, Nigeria

Emmanuel Gbenga Olumayede\*, B. Babalola and I. Oghenovo Department of Industrial Chemistry, Federal University Oye-Ekiti,

provided the original work is properly cited.

\*Address all correspondence to: emmanuel.olumayede@fuoye.edu.ng

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Part Fibre Toxicol., 2010; **7**: 2.

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CA, USA, 1ST Edition, 1990

(10): 1161-1208.

7: 7-13.

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[48] Kagi JHR, Kogima Y. Chemistry and biochemistry of metallothionein. Boston: Birkhäuser, eds. 1987. pp. 25-61

[49] Halliwell B, Gutterridge, JMC. Free radical and antioxidant protection: Mechanism and significant in toxicity and diseases. Human Toxicity, 1988;

[51] Eichhorn GL, Butzow JJ, Shin YA. Some effects of metal ions on DNA structure and genetic information

[50] Aust SD, Morehouse LA, Thomas CE. The role of metals in oxygen radical reactions, J. Free Rad.

Biol. Med. 1985; 1: 3-25

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2012;42:86-93.

1987; 25-61.

222: 1-15,

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[37] Andujar, P., et al., *Respiratory effects of manufactured nanoparticles.* Rev Mal Respir, 2011; 28(8): p. e66–e75.

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[39] Braakhuis HM, et al., *Physicochemical characteristics of nanomaterials that affect pulmonary inflammation.* Part. Fibre Toxicol, 2014; 11: 18.

[40] Jud C, et al., *Nanomaterials and the human lung: what is known and what must be deciphered to realise their potential advantages?* Swiss Med. Weekly, 2013; 143: 13758.

[41] Jones RM, Neef N. Interpretation and prediction of inhaled drug

particle accumulation in the lung and its associated toxicity. Xenobiotica. 2012;42:86-93.

[42] Geiser M, Kreyling WG. *Deposition and biokinetics of inhaled nanoparticles.* Part Fibre Toxicol., 2010; **7**: 2.

[43] Heyder J, Svarten, MU. Basic principles of particle behavior in the human respiratory tract, In: Bisgaard H, O'Callaghan C, Smaldone GC, Eds. Drug Delivery to the Lungs. Lung Biology in Health and Disease, Marcel Dekker; New York: 2002. p. 21-45.

[44] Kagi JHR, Kogima Y., eds. Chemistry and Biochemistry of metallothionein. Boston: Birkhäuser, 1987; 25-61.

[45] Slater TF. Free-radical mechanisms in tissue injury, Biochem Journal 1984; 222: 1-15,

[46] Joesten MD, Johnson DO, Netterville JT, Wood JL. World of Chemistry, Brooks/cole. Pacific Grove, CA, USA, 1ST Edition, 1990

[47] Vako M, Morris H, Cronin MT. Metals, toxicity and oxidative stress, Current Medicinal Chemistry, 2005; 12 (10): 1161-1208.

[48] Kagi JHR, Kogima Y. Chemistry and biochemistry of metallothionein. Boston: Birkhäuser, eds. 1987. pp. 25-61

[49] Halliwell B, Gutterridge, JMC. Free radical and antioxidant protection: Mechanism and significant in toxicity and diseases. Human Toxicity, 1988; 7: 7-13.

[50] Aust SD, Morehouse LA, Thomas CE. The role of metals in oxygen radical reactions, J. Free Rad. Biol. Med. 1985; 1: 3-25

[51] Eichhorn GL, Butzow JJ, Shin YA. Some effects of metal ions on DNA structure and genetic information

transfer. Proc. Int. Symp. Biomol., Struct., Interactions, Suppl. J. Biosci. 1985; 8 (3&4): 527-535.

[52] Morris DL. DNA-bound metal ions: recent developments. BioMol Concepts 2014; 5(5): 397-407

[53] Eichhorn, GL. In advances in Inorganic Biochemistry (eds Eichhorn, GL and Marzilli) (New York, Elsevier) Vol. 3. P2

[54] Ruby MV, Schoof R, Brattin W, Goldade M, Post G, Harnois M, Mosby DE, Casteel SW, Berti W, Carpenter M, et al. Advances in evaluating the oral bioavailability of inorganics in soil for use in human health risk assessment. Environ. Sci. Technol., 1999; 33: 3697-3705.

[55] Ng JC, Juhasz A, Smith E, Naidu R. Assessing the bioavailability and bioaccessibility of metals and metalloids, Environ. Sci. Pollut. Res. 2015; 22 : 8802-8825

[56] Huang X, Betha R, Tan LY, Balasubramanian R. Risk assessment of bioaccessible trace elements in smoke haze aerosols versus urban aerosols using simulated lung fluids. Atmos. Environ. 2016; 125: 505-511

[57] Cui X, Xiang P, He R, Juhasz A, Ma L. Advances in in vitro methods to evaluate oral bioaccessibility of PAHs and PBDEs in environmental matrices. Chemosphere 2016; 150, 378-389

[58] Caboche J, Esperanza P, Bruno M, Alleman LY. Development of an in vitro method to estimate lung bioaccessibility of metals from atmospheric particles. Journ. Environ. Monit. 2011; 13: 621-630

[59] Boisa N, Elom N, Dean JR, Deary ME, Bird G, Entwistle JA. Development and application of an inhalation bioaccessibility method (IBM) for lead in the PM10 size fraction of soil. Environ. Inter.,

2014; 70: 132-142. Doi: 10.1016/j. envint.2014.05.021.

[60] Luo X.-san, Yu S, Li X.-dong. The mobility, bioavailability, and human bioaccessibility of trace elements in urban soils of Hong Kong, Applied Geochemistry, 2012; 27 (5): 995-1004.

[61] Dean JR, Elom NI, Entwistle JA. Use of stimulated epithelium lung fluid in assessing the human health risk of Pb in urban street dust, Sci. of the Total Environment, 2016; http://dx.doi.org/10.1016/j. sciotenv.2016.11.085

[62] Olumayede EG, Oguntimehin I, Babalola B, Ojiodu C, Akinyeye RO, Sodipe OG, Uche J, Ojo A. Development of tracheobronchial fluid for in vitro bioaccessibility assessment of particulates-bound trace elements. MethodsX, 2019; (6): 1944- 1949. https://doi.org/10.1016/j. mex.2019.07.027

[63] Pelfrene A, Cave MR, Wragg J, Douay F. In vitro investigations of human bioaccessibility from reference materials using simulated lung fluids, International Journal of Environmental Research and Public Health, 2017; 14: 112.

[64] Fernánndez Espínosa JA, Ternero Rodríguez M, Barragán de la Rosa FJ, Jiménez Sánchez, JC. Atmos. Environ. 2002; 36: 773-780

[65] Tang Z, Hu X, Chen Y, Qiao J, Lian H. Assessment if in vitro inhalation bioaccessibility of airborne particlebound potentially toxic elements collected using quartz and PTFE filter. Atmospheric Environment 2019; 196: 118-124.

[66] Wiseman CLS, Zereini F. Characterizing metal (loid) solubility in airborne PM10, PM2.5, and PM1 in Frankfurt, Germany using stimulated lung fluid. Atmos. Environ.

**95**

*Trace Elements in Urban Particulate Matters: Variations in Serum Levels, Inhalation...*

2017; 42: 39-44. Doi.org/10.1016/j.

[75] Forte G, Bocco B, Pisano A, et al. The levels of trace elements in sputum as biomarkers for idiopathic pulmonary fibrosis, Chemosphere 2021; 271(1): 129514. Doi:10.1016/j.

chemosphere.2020.129514.

[76] Oh J, Shin SH, Choi R, Kim S, Park HD, Kim SY, Han SA, Koh WJ, Lee SY. Assessment of 7 trace elements

tuberculous mycobacterial lung disease, J Trace Element Med Biol. 2019 May;

[77] Tonelli M, Wiebe N, Hemmelgarn, B et al. Trace elements in haemodailysis

patient: a systematic review and meta-analysis, BMC Med 2009; 7: 29 htpps://doi.org/10.1186/171-7015-7-25.

in serum of patients with non-

53:84-90

[74] Hutchinson J, Fogarty A, Hubbard R, McKeever T. Global incidence and mortality of idiopathic pulmonary fibrosis: a systematic review. Eur Respir J. 2015; 46(3):795-806

jtemb.2017.04.001.

*DOI: http://dx.doi.org/10.5772/intechopen.96364*

2014; 89: 282-289 doi:10.1016/j.

[67] Alpofead JAH, Davidson CM, Littlejohn D. A novel two-step sequential solubility or dissolution tests for potentially toxic elements in inhalable particulate matter transported

into the gastrointestinal tract by mucociliary clearance. Anal Bioanal

[68] Guo CH, Liu P, Hsia S, Chuang C, Chen P. Role of certain trace minerals in oxidative stress, imflammation, CD4/CD8 lymphocyte ratios and lung function in asthmatic patients. Ann. Clin. Biochem. 2011; 48: 344-351

[69] Ermis B, Armutcu F, Gurel A, Kar L, Demircan N, Altin R, Daemirel E. Trace elements status in children with bronchial asthma. Eur. J Gen Med.

[70] Niu J, Liberda EN, Qu S, Guo X, Li X, Zhang J, et al. The role of metal components in the cardiovascular effects of PM2.5, PLoS One, 2013;

[71] Sarkar S, Yadav P, Trivedi R, Bansal AK, Bhatnagar D. Cadmiuminduced lipid peroxidation and the status of the antioxidant system in rat tissue. Journal of Trace Elements in Medicine and Biology, 1995;

[72] Kirkham P, Rahman I. Oxidative

antioxidants as a therapeutic strategy. Pharmacology & Therapeutics, 2006;

Istolesi M, Rosi E, Prasse A, Rota E, Voltolini L. Trace elements in fluids lining the respiratory system of patients with idiopathic pulmonary fibrosis and diffuse lung diseases. Journal of trace Element Medicine and Biology,

stress in asthma and COPD:

[73] Bargagli E, Lavorini F, P

Chem. 2017; 409: 3165-3174

2004; 1(1): 4-8.

8(12): e83782.

9(3): 144-149

111: 476-494.

atmosenv.2014.02.055

*Trace Elements in Urban Particulate Matters: Variations in Serum Levels, Inhalation... DOI: http://dx.doi.org/10.5772/intechopen.96364*

2014; 89: 282-289 doi:10.1016/j. atmosenv.2014.02.055

*Trace Elements and Their Effects on Human Health and Diseases*

2014; 70: 132-142. Doi: 10.1016/j.

[60] Luo X.-san, Yu S, Li X.-dong. The mobility, bioavailability, and human bioaccessibility of trace elements in urban soils of Hong Kong, Applied Geochemistry, 2012; 27 (5): 995-1004.

[61] Dean JR, Elom NI, Entwistle JA. Use of stimulated epithelium lung fluid in assessing the human health risk of Pb in urban street dust, Sci. of the Total Environment, 2016; http://dx.doi.org/10.1016/j.

[62] Olumayede EG, Oguntimehin I, Babalola B, Ojiodu C, Akinyeye RO, Sodipe OG, Uche J, Ojo A. Development

of tracheobronchial fluid for in vitro bioaccessibility assessment of particulates-bound trace elements.

MethodsX, 2019; (6): 1944- 1949. https://doi.org/10.1016/j.

[63] Pelfrene A, Cave MR,

Health, 2017; 14: 112.

2002; 36: 773-780

118-124.

of human bioaccessibility from reference materials using simulated lung fluids, International Journal of Environmental Research and Public

Wragg J, Douay F. In vitro investigations

[64] Fernánndez Espínosa JA, Ternero Rodríguez M, Barragán de la Rosa FJ, Jiménez Sánchez, JC. Atmos. Environ.

[65] Tang Z, Hu X, Chen Y, Qiao J, Lian H. Assessment if in vitro inhalation bioaccessibility of airborne particlebound potentially toxic elements collected using quartz and PTFE filter. Atmospheric Environment 2019; 196:

[66] Wiseman CLS, Zereini F.

in airborne PM10, PM2.5, and PM1 in Frankfurt, Germany using stimulated lung fluid. Atmos. Environ.

Characterizing metal (loid) solubility

mex.2019.07.027

envint.2014.05.021.

sciotenv.2016.11.085

transfer. Proc. Int. Symp. Biomol., Struct., Interactions, Suppl. J. Biosci.

[53] Eichhorn, GL. In advances in Inorganic Biochemistry (eds Eichhorn, GL and Marzilli) (New York, Elsevier)

[52] Morris DL. DNA-bound metal ions: recent developments. BioMol Concepts

1985; 8 (3&4): 527-535.

2014; 5(5): 397-407

[54] Ruby MV, Schoof R, Brattin W, Goldade M, Post G, Harnois M, Mosby DE, Casteel SW, Berti W, Carpenter M, et al. Advances in evaluating the oral bioavailability of inorganics in soil for use in human health risk assessment. Environ. Sci. Technol., 1999; 33: 3697-3705.

[55] Ng JC, Juhasz A, Smith E,

[56] Huang X, Betha R, Tan LY,

Environ. 2016; 125: 505-511

2015; 22 : 8802-8825

Naidu R. Assessing the bioavailability and bioaccessibility of metals and metalloids, Environ. Sci. Pollut. Res.

Balasubramanian R. Risk assessment of bioaccessible trace elements in smoke haze aerosols versus urban aerosols using simulated lung fluids. Atmos.

[57] Cui X, Xiang P, He R, Juhasz A, Ma L. Advances in in vitro methods to evaluate oral bioaccessibility of PAHs and PBDEs in environmental matrices. Chemosphere 2016; 150, 378-389

[58] Caboche J, Esperanza P, Bruno M, Alleman LY. Development of an in vitro method to estimate lung bioaccessibility of metals from atmospheric particles. Journ. Environ. Monit. 2011; 13: 621-630

[59] Boisa N, Elom N, Dean JR, Deary ME, Bird G, Entwistle JA. Development and application of an inhalation bioaccessibility method (IBM) for lead in the PM10 size fraction of soil. Environ. Inter.,

Vol. 3. P2

**94**

[67] Alpofead JAH, Davidson CM, Littlejohn D. A novel two-step sequential solubility or dissolution tests for potentially toxic elements in inhalable particulate matter transported into the gastrointestinal tract by mucociliary clearance. Anal Bioanal Chem. 2017; 409: 3165-3174

[68] Guo CH, Liu P, Hsia S, Chuang C, Chen P. Role of certain trace minerals in oxidative stress, imflammation, CD4/CD8 lymphocyte ratios and lung function in asthmatic patients. Ann. Clin. Biochem. 2011; 48: 344-351

[69] Ermis B, Armutcu F, Gurel A, Kar L, Demircan N, Altin R, Daemirel E. Trace elements status in children with bronchial asthma. Eur. J Gen Med. 2004; 1(1): 4-8.

[70] Niu J, Liberda EN, Qu S, Guo X, Li X, Zhang J, et al. The role of metal components in the cardiovascular effects of PM2.5, PLoS One, 2013; 8(12): e83782.

[71] Sarkar S, Yadav P, Trivedi R, Bansal AK, Bhatnagar D. Cadmiuminduced lipid peroxidation and the status of the antioxidant system in rat tissue. Journal of Trace Elements in Medicine and Biology, 1995; 9(3): 144-149

[72] Kirkham P, Rahman I. Oxidative stress in asthma and COPD: antioxidants as a therapeutic strategy. Pharmacology & Therapeutics, 2006; 111: 476-494.

[73] Bargagli E, Lavorini F, P Istolesi M, Rosi E, Prasse A, Rota E, Voltolini L. Trace elements in fluids lining the respiratory system of patients with idiopathic pulmonary fibrosis and diffuse lung diseases. Journal of trace Element Medicine and Biology,

2017; 42: 39-44. Doi.org/10.1016/j. jtemb.2017.04.001.

[74] Hutchinson J, Fogarty A, Hubbard R, McKeever T. Global incidence and mortality of idiopathic pulmonary fibrosis: a systematic review. Eur Respir J. 2015; 46(3):795-806

[75] Forte G, Bocco B, Pisano A, et al. The levels of trace elements in sputum as biomarkers for idiopathic pulmonary fibrosis, Chemosphere 2021; 271(1): 129514. Doi:10.1016/j. chemosphere.2020.129514.

[76] Oh J, Shin SH, Choi R, Kim S, Park HD, Kim SY, Han SA, Koh WJ, Lee SY. Assessment of 7 trace elements in serum of patients with nontuberculous mycobacterial lung disease, J Trace Element Med Biol. 2019 May; 53:84-90

[77] Tonelli M, Wiebe N, Hemmelgarn, B et al. Trace elements in haemodailysis patient: a systematic review and meta-analysis, BMC Med 2009; 7: 29 htpps://doi.org/10.1186/171-7015-7-25.

**97**

**Chapter 7**

**Abstract**

**1. Introduction**

Analysis of *Aristolochia longa* L.

In recent time, the therapeutic use of medicinal plants has increased all over the world. The efficacy of herbs for curative purposes is often accounted of its mineral and organic constituents. Neutron activation analysis (INAA) has been applied to mineral determination of Aristolochia Longa (bereztem), medicinal plant used to cure some diseases observed in Algeria especially cancer. In this work the mass fractions of Cr (15.22 ± 3.5 μg/g), Na (269.98 ± 25.01 μg/g), La (0.478 ± 0.041 μg/g), K (1.33 ± 0.23 μg/g), Br (1.2 ± 0.19 μg/g), As (0.697 ± 0.038) and Sb (66.09 ± 11.24 μg/g), were determined. This herb was collected from Taourirt Aden Berber village situated in Northern Algeria. Five elements were quantified in certified AIEA standards IAEA-V10 and IAEA-SL1 for checking the accuracy of our procedure. It was noteworthy the values obtained from this work are in good agreement with the certified values, the Z-score values for all elements were |Z| < 3. We believe that herb is natural and harmless compared with chemical drugs. Unfortunately the potential toxicity due to the Aristolochia Acids content has required the analysis of Aristolochia Longa by CG/MS and HPLC to highlight this compound. The standard of Aristolochic Acid (Sigma A5512-25 mg Yellow powder

**Keywords:** Aristolochia Longa, INAA, organic compounds, public health, Algeria

Bereztem is the common name of Aristolochia Longa, this herb with a delicate aromatic odor is wrongly used as medicinal plant in Algeria [1, 2] and other countries. We find these plants in the temperate and tropical regions [3]. Since antiquity various *Aristolochia* and *Asarum* species have been used in herbal medicines in obstetrics and in treatment of Intestinal affections, coetaneous diseases, wounds, heart palpitation or snakebite, festering wounds, and tumors [4, 5], indeed 60% of drugs approved for cancer treatment are of natural origin [6, 7]. B. Benarba report the cytotoxic and apoptogenic activities of an aqueous extract of *A. longa* in the Burkitt's lymphoma BL41 cell line [8]. Considered also as antidote against some poisonings [9]. It was reported [10, 12] that plants remain in use today especially in the Chinese medicine. All parts of the plant are used in herbal preparations, and aristolochic acids are present in the roots, stems, leaves, and fruit [11, 12]. Exposure to this acid could potentially occur through the ingestion or skin contact to treat wounds, note no published studies of skin absorption of aristolochic acids in humans or experimental animals were found. However certain plant as canadense

Medicinal Plant from Algeria

*Zohra Lamari and Houria Negache*

lot # wxbb6331VPCODE) was used as reference.

**Chapter 7**

## Analysis of *Aristolochia longa* L. Medicinal Plant from Algeria

*Zohra Lamari and Houria Negache*

#### **Abstract**

In recent time, the therapeutic use of medicinal plants has increased all over the world. The efficacy of herbs for curative purposes is often accounted of its mineral and organic constituents. Neutron activation analysis (INAA) has been applied to mineral determination of Aristolochia Longa (bereztem), medicinal plant used to cure some diseases observed in Algeria especially cancer. In this work the mass fractions of Cr (15.22 ± 3.5 μg/g), Na (269.98 ± 25.01 μg/g), La (0.478 ± 0.041 μg/g), K (1.33 ± 0.23 μg/g), Br (1.2 ± 0.19 μg/g), As (0.697 ± 0.038) and Sb (66.09 ± 11.24 μg/g), were determined. This herb was collected from Taourirt Aden Berber village situated in Northern Algeria. Five elements were quantified in certified AIEA standards IAEA-V10 and IAEA-SL1 for checking the accuracy of our procedure. It was noteworthy the values obtained from this work are in good agreement with the certified values, the Z-score values for all elements were |Z| < 3. We believe that herb is natural and harmless compared with chemical drugs. Unfortunately the potential toxicity due to the Aristolochia Acids content has required the analysis of Aristolochia Longa by CG/MS and HPLC to highlight this compound. The standard of Aristolochic Acid (Sigma A5512-25 mg Yellow powder lot # wxbb6331VPCODE) was used as reference.

**Keywords:** Aristolochia Longa, INAA, organic compounds, public health, Algeria

#### **1. Introduction**

Bereztem is the common name of Aristolochia Longa, this herb with a delicate aromatic odor is wrongly used as medicinal plant in Algeria [1, 2] and other countries. We find these plants in the temperate and tropical regions [3]. Since antiquity various *Aristolochia* and *Asarum* species have been used in herbal medicines in obstetrics and in treatment of Intestinal affections, coetaneous diseases, wounds, heart palpitation or snakebite, festering wounds, and tumors [4, 5], indeed 60% of drugs approved for cancer treatment are of natural origin [6, 7]. B. Benarba report the cytotoxic and apoptogenic activities of an aqueous extract of *A. longa* in the Burkitt's lymphoma BL41 cell line [8]. Considered also as antidote against some poisonings [9]. It was reported [10, 12] that plants remain in use today especially in the Chinese medicine. All parts of the plant are used in herbal preparations, and aristolochic acids are present in the roots, stems, leaves, and fruit [11, 12]. Exposure to this acid could potentially occur through the ingestion or skin contact to treat wounds, note no published studies of skin absorption of aristolochic acids in humans or experimental animals were found. However certain plant as canadense

leaves cause the dermatitis [13]. The dried rhizome of Aristolochia Longa is the one of the part frequently used often without other ingredients. Several reports indicate the use of complementary and alternative medicine (CAM) and a lot of people in Algeria believe that herb is natural and harmless compared with chemical drugs. Unfortunately, they are unaware of its adverse biological effects. The Aristolochic Acids content, alkaloid components are known to be mutagenic and carcinogenic [14]. The clinical syndrome to the Chinese plants Nephropathy (NCP) was reported in first in Belgium for the women having followed a Chinese slimming diet in 1992 after consumption of herbal weight loss preparations containing Aristolochia Fangehi by inadvertence instead Stephania Tetrandra [15]. Kupchan and Doskovitch 1962 [16], have tested the antitumor effects of aristolochic acids in mice and in clinical trials. But when Jackson et al. [17] showed the neph-rotoxicity of aristolochic acid the trials were discontinued. Mix et al. [18]; Kumar et al. [19] Described twelve Aristolochic Acid analogues, the major compounds of AAS include AAI and its demethoxylates derivative, AAII, generally the levels of AAI are higher than AAII, the **Figure 1** shown their structures. The metabolites are excreted in the urine and the feces. Reported half-lives in New Zealand White rabbits for aristolochic acids I and II were 0.12 hours and 0.27 hours, respectively. Studies in rats show that the metabolites of aristolochic acid I are excreted within 24 hours, whereas metabolites of aristolochic acid II are still present in the urine at 72 hours. Furthermore the curative properties of this plant are based only on traditional knowledge and in our country there are no procedures and regulations applicable about the use and marketing to the healing plants. Regrettably Aristolochia Longa is easily obtained from local markets. Unlike this herb is forbidden in several countries USA [20], Canada, Taiwan, France, and Belgium. The European Commission (EC) (2000) has prohibited aristolochic acid and its salts, as well as Aristolochia species, and their preparations in cosmetic products. The trace element present in *Aristolochia longa* L. rhizomes; determined by Neutron activation analysis (INAA) can may be explain some therapeutic activities. At the same time two (02) methods have been used for the identification of aristololochic acids (AAS). We made Gas chromatography – Mass spectrometry (CG/MS) and High performance Liquid chromatography (HPLC). This work can constitute a position paper to better use of this natural product by the cancer patients who take this herb.

AAs I (AAI) and II (AAII) (EMEA 2000).

**99**

**Table 1.**

our elements.

*Analysis of* Aristolochia longa *L. Medicinal Plant from Algeria*

In order to analyze Aristolochia longa L., Rhizomes were collected in May 2016 from Taourirt Aden, Algerian village situated in Kabylia region at 120 km south of Algiers city, Algeria. The vegetal material was washed extensively in distillated water as to remove superficial dust. And then dried at room temperature for one week-end. The dry and hard form of these roots was ground in an electric laboratory blender. One part of the fine powder obtained was prepared for neutron Activation Analysis. The triplicate samples were packed in polyethylene thin target and irradiated during four hours (04) in NUR Algerian reactor, 1 MW research reactor. After 04 and 08 days of delay time the acquisitions were done for determination of Cr, Na, La, K, Br, As and Sb. The analysis was done using HpGe – Canberra detector and the elemental concentrations were performed by Calcon software. The count time was twenty (20) hours for medicinal plants and about five (05) hours for the standards. The certified reference material SDM-2TM Lake (sediment marine lyophilized) was used for calibration. The quality control was done using IAEA biological material V10 (hay powder) and AIEA non biological material SL-1 (lake sediment). Another part of this powder herb was used for the identification of Aristolochic Acids by CG/MS; and HPLC techniques. Many extracted methods have been reported in literature [21]. The extract of AA was prepared by adding 10 ml of methanol to 10 g of *A. longa* dry rhizomes powder for the first extraction and 20 ml of light petroleum for the second extraction, solvent extraction the most commonly used for extraction of AAs [22]. After 24 h of maceration under magnetic stirring at room temperature, the mixture was centrifuged, filtered and then concentrated in a rotary vacuum evaporator (The number of siphon age is ten) indeed the quantification of AA in extract products is less complicated as compared to herbal preparations. However to avoid the loss of chemical information's the extraction method should be no selective to explain the therapeutic aspect. The extracted material was analyzed by CG/MS and HPLC in order to detect the potential presence of AAs in Aristolochia Longa. The standard of Aristolochic Acid recently acquired (Sigma A5512–25 mg Yellow powder lot # wxbb6331VPCODE.) was used as reference. It should be noted that the Aristolochic acids compounds are produced commercially only as reference standards and as

**Table 1** show the Algerian medicinal plant studied with the botanical name, common name and the part used for treatment. Five elements were quantified in certified AIEA standards IAEA-V10 and IAEA-SL1 for checking the accuracy of our procedure. The values obtained were showed in **Table 2** with the reported certified values. It was noteworthy the values obtained from this work are in good agreement with the certified values; The **Figure 2** presents graphically the plot of Z-score for

**Common name Botanical name Family Part used for treatments**

Berztem Aristoloshia Longa Aristolochiaceae Root, aerial part

*Botanical name and parts used of the medicinal plant studied.*

*DOI: http://dx.doi.org/10.5772/intechopen.95298*

**2. Experimental**

research chemicals [12, 23].

**3. Results and discussion**

## **2. Experimental**

*Trace Elements and Their Effects on Human Health and Diseases*

leaves cause the dermatitis [13]. The dried rhizome of Aristolochia Longa is the one of the part frequently used often without other ingredients. Several reports indicate the use of complementary and alternative medicine (CAM) and a lot of people in Algeria believe that herb is natural and harmless compared with chemical drugs. Unfortunately, they are unaware of its adverse biological effects. The Aristolochic Acids content, alkaloid components are known to be mutagenic and carcinogenic [14]. The clinical syndrome to the Chinese plants Nephropathy (NCP) was reported in first in Belgium for the women having followed a Chinese slimming diet in 1992 after consumption of herbal weight loss preparations containing Aristolochia Fangehi by inadvertence instead Stephania Tetrandra [15]. Kupchan and Doskovitch 1962 [16], have tested the antitumor effects of aristolochic acids in mice and in clinical trials. But when Jackson et al. [17] showed the neph-rotoxicity of aristolochic acid the trials were discontinued. Mix et al. [18]; Kumar et al. [19] Described twelve Aristolochic Acid analogues, the major compounds of AAS

include AAI and its demethoxylates derivative, AAII, generally the levels of AAI are higher than AAII, the **Figure 1** shown their structures. The metabolites are excreted in the urine and the feces. Reported half-lives in New Zealand White rabbits for aristolochic acids I and II were 0.12 hours and 0.27 hours, respectively. Studies in rats show that the metabolites of aristolochic acid I are excreted within 24 hours, whereas metabolites of aristolochic acid II are still present in the urine at 72 hours. Furthermore the curative properties of this plant are based only on traditional knowledge and in our country there are no procedures and regulations applicable about the use and marketing to the healing plants. Regrettably Aristolochia Longa is easily obtained from local markets. Unlike this herb is forbidden in several countries USA [20], Canada, Taiwan, France, and Belgium. The European Commission (EC) (2000) has prohibited aristolochic acid and its salts, as well as Aristolochia species, and their preparations in cosmetic products. The trace element present in *Aristolochia longa* L. rhizomes; determined by Neutron activation analysis (INAA) can may be explain some therapeutic activities. At the same time two (02) methods have been used for the identification of aristololochic acids (AAS). We made Gas chromatography – Mass spectrometry (CG/MS) and High performance Liquid chromatography (HPLC). This work can constitute a position paper to better use of

this natural product by the cancer patients who take this herb.

AAs I (AAI) and II (AAII) (EMEA 2000).

*Chemical structure of nitrophenanthrene carboxylic acids.*

**98**

**Figure 1.**

In order to analyze Aristolochia longa L., Rhizomes were collected in May 2016 from Taourirt Aden, Algerian village situated in Kabylia region at 120 km south of Algiers city, Algeria. The vegetal material was washed extensively in distillated water as to remove superficial dust. And then dried at room temperature for one week-end. The dry and hard form of these roots was ground in an electric laboratory blender. One part of the fine powder obtained was prepared for neutron Activation Analysis. The triplicate samples were packed in polyethylene thin target and irradiated during four hours (04) in NUR Algerian reactor, 1 MW research reactor. After 04 and 08 days of delay time the acquisitions were done for determination of Cr, Na, La, K, Br, As and Sb. The analysis was done using HpGe – Canberra detector and the elemental concentrations were performed by Calcon software. The count time was twenty (20) hours for medicinal plants and about five (05) hours for the standards. The certified reference material SDM-2TM Lake (sediment marine lyophilized) was used for calibration. The quality control was done using IAEA biological material V10 (hay powder) and AIEA non biological material SL-1 (lake sediment). Another part of this powder herb was used for the identification of Aristolochic Acids by CG/MS; and HPLC techniques. Many extracted methods have been reported in literature [21]. The extract of AA was prepared by adding 10 ml of methanol to 10 g of *A. longa* dry rhizomes powder for the first extraction and 20 ml of light petroleum for the second extraction, solvent extraction the most commonly used for extraction of AAs [22]. After 24 h of maceration under magnetic stirring at room temperature, the mixture was centrifuged, filtered and then concentrated in a rotary vacuum evaporator (The number of siphon age is ten) indeed the quantification of AA in extract products is less complicated as compared to herbal preparations. However to avoid the loss of chemical information's the extraction method should be no selective to explain the therapeutic aspect. The extracted material was analyzed by CG/MS and HPLC in order to detect the potential presence of AAs in Aristolochia Longa. The standard of Aristolochic Acid recently acquired (Sigma A5512–25 mg Yellow powder lot # wxbb6331VPCODE.) was used as reference. It should be noted that the Aristolochic acids compounds are produced commercially only as reference standards and as research chemicals [12, 23].

## **3. Results and discussion**

**Table 1** show the Algerian medicinal plant studied with the botanical name, common name and the part used for treatment. Five elements were quantified in certified AIEA standards IAEA-V10 and IAEA-SL1 for checking the accuracy of our procedure. The values obtained were showed in **Table 2** with the reported certified values. It was noteworthy the values obtained from this work are in good agreement with the certified values; The **Figure 2** presents graphically the plot of Z-score for our elements.


**Table 1.**

*Botanical name and parts used of the medicinal plant studied.*


**Table 2.**

*Quality Control assessment results (*μ*g/g) for the AIEA - certified reference material Samples.*

**Figure 2.** *Z-score values for the elements determined in IAEA standards V10 and SL1.*

**Table 3** report the elemental concentrations obtained from this work and shows the usefulness of using INAA for the elemental determination, the La, K, Br, As are present at trace levels and the Cr, Sb was found at minor level and Na at the major level. Owing to its high toxicity, the identification of AAs is obviously important indeed these acids cause Aristolochic Acids Nephropathy (NAA), the chronic renal failure according to Grollman et al. [24] and urotherial carcinomas [25, 26].

A new American study reveals that these AAs are more carcinogen than the tobacco [27]. The toxicity of the aristolochic acids has been studied and reported by Mengs and Stotzem [28]. When The Arirstolochic Acids extracted from a medicinal plant are traditionally used in China to cure some diseases, the arthritis and the other inflammations. It has been shown by various authors that these Aristolochic acids have directly toxic on the human gene TP53 (gene suppressor of cancer) [29]. No mutations were identified in rats with chronic renal failure not exposed to aristolochic acids. Similar findings have been reported in humans [30]. The complexity of herbal nomenclature systems used in traditional Chinese medicines may have contributed to the potential exposure to aristolochic acids. As well as the

**101**

**Figure 3.**

*# wxbb6331VPCODE)*

*Analysis of* Aristolochia longa *L. Medicinal Plant from Algeria*

similarity of the Chinese names for *Aristolochia* species and other innocuous herbs

Even more similar Japanese and Chinese names refer to different plants in Japan and China [32], explained the outbreak of Chinese herb nephropathy in Japan by the substitution of that plant species in Japanese preparations of Chinese herbal medicines. In this study we are analysed the rhizome of Aristolochia Longa to identify the aristolochic acid much to our surprise this organic compound is not reveled in our herb. The **Figures 3** and **4** shows the results obtained by CG/MS and HPLC, the characteristic retention times of AAI Acid present in our reference standard are 42.88 min and 21.758 min relative to the analysis by CG/MS and

*CG/MS spectrum analysis of our herb (rhizome) and (AAI) standard. (Sigma A5512–25 mg Yellow powder lot* 

can increase risk of inadvertent exposures to aristolochic acids [31].

**Element Aristoloshia Longa** Cr 15.22 ± 3.5 Na 269.98 ± 25.01 La 0.478 ± 0.041 K 1.33 ± 0.23 Br 1.2 ± 0.19 As 0.697 ± 0.038 Sb 66.09 ± 11.24

*Elemental Concentrations (*μ*g/g) for Aristoloshia Longa rhizome.*

*DOI: http://dx.doi.org/10.5772/intechopen.95298*

HPLC respectively.

**Table 3.**

#### *Analysis of* Aristolochia longa *L. Medicinal Plant from Algeria DOI: http://dx.doi.org/10.5772/intechopen.95298*

similarity of the Chinese names for *Aristolochia* species and other innocuous herbs can increase risk of inadvertent exposures to aristolochic acids [31].

Even more similar Japanese and Chinese names refer to different plants in Japan and China [32], explained the outbreak of Chinese herb nephropathy in Japan by the substitution of that plant species in Japanese preparations of Chinese herbal medicines. In this study we are analysed the rhizome of Aristolochia Longa to identify the aristolochic acid much to our surprise this organic compound is not reveled in our herb. The **Figures 3** and **4** shows the results obtained by CG/MS and HPLC, the characteristic retention times of AAI Acid present in our reference standard are 42.88 min and 21.758 min relative to the analysis by CG/MS and HPLC respectively.


#### **Table 3.**

*Trace Elements and Their Effects on Human Health and Diseases*

K\* 24.65 ± 2.96 21 ± 2

Na\* 0.692 ± 0.064 0.5 ± 0.3

**Element IAEA-V10 IAEA-SL1**

*Quality Control assessment results (*μ*g/g) for the AIEA - certified reference material Samples.*

Cr 6.42 ± 0.798 6.5 ± 0.75 94.92 ± 8.54 104 ± 9

Br 10.82 ± 1.73 8 ± 2 6.82 ± 1.73 9.79 ± 1.58

**Measured Reported Measured Reported**

*Z-score values for the elements determined in IAEA standards V10 and SL1.*

**Table 3** report the elemental concentrations obtained from this work and shows the usefulness of using INAA for the elemental determination, the La, K, Br, As are present at trace levels and the Cr, Sb was found at minor level and Na at the major level. Owing to its high toxicity, the identification of AAs is obviously important indeed these acids cause Aristolochic Acids Nephropathy (NAA), the chronic renal

failure according to Grollman et al. [24] and urotherial carcinomas [25, 26]. A new American study reveals that these AAs are more carcinogen than the tobacco [27]. The toxicity of the aristolochic acids has been studied and reported by Mengs and Stotzem [28]. When The Arirstolochic Acids extracted from a medicinal plant are traditionally used in China to cure some diseases, the arthritis and the other inflammations. It has been shown by various authors that these Aristolochic acids have directly toxic on the human gene TP53 (gene suppressor of cancer) [29]. No mutations were identified in rats with chronic renal failure not exposed to aristolochic acids. Similar findings have been reported in humans [30]. The complexity of herbal nomenclature systems used in traditional Chinese medicines may have contributed to the potential exposure to aristolochic acids. As well as the

**100**

**Figure 2.**

Sb *\**

**Table 2.**

*Values given in mg/g.*

*Elemental Concentrations (*μ*g/g) for Aristoloshia Longa rhizome.*

#### **Figure 3.**

*CG/MS spectrum analysis of our herb (rhizome) and (AAI) standard. (Sigma A5512–25 mg Yellow powder lot # wxbb6331VPCODE)*

**Figure 4.**

*HPLC spectrum analysis of bereztem roots and (AAI) standard. (Sigma A5512–25 mg Yellow powder lot # wxbb6331VPCODE)*

The Aristolochic acids content of plants varies depending for the same plant species, where it was grown, the time of year, and other factors, that might explain our results? The sample matrix components can influence the limits of detection for Aristolochic acids. We suggested also the insufficient amount of our plant we used 10 mg fine powder of bereztem roots. Although the protocol experimental described by Cherif H.S., and all has been reproduced, in our work, these authors identified the Aristolochic acid (AAI) in the rhizome of bereztem collected in the other city of Algeria: Blida (smell city) located about 47 km in southwest of Algiers. While our plant is collected in the region of Taourirt Aden in (kabylia). Broad range of biological activity of AAs, beneficial as well as adverse effects was reported by Kupchan and Doskotch [33]; therefore it would be interesting to determine the organic composition, it is known that the essential oils contained in the rhizome and aerial part of this herb are mainly responsible for the antimicrobial and cytotoxic effect [34]. And then instead to banned the use of herbal remedy containing acid aristolochic it will be possible to separate the useful from the toxic fractions of plant.

**103**

*Analysis of* Aristolochia longa *L. Medicinal Plant from Algeria*

and Education Act (DSHEA) of 1994 (FDA 1995) [36].

INAA Instrumental Neutron activation analysis CAM Complementary and Alternative Medicine

NAA Aristolochic Acids Nephropathy

AAs Aristolochic Acids AAI Acide Aristolochique I

EC European Commission

EMEA European Medicines Agency

HpGe-Detector High Purity Germanium Detector

NCP Clinical Syndrome to the Chinese plants Nephropathy

AAII Acide Aristolochique (demethoxylates derivative)

INCC National Institute of Forensic Science and Criminology, Algeria

CG/MS Gas chromatography – Mass spectrometry HPLC High performance Liquid chromatography IARC International Agency for Research on Cancer

Seven elements have been determined in Aristiolochia Longa. L using INAA, technique usually quite for herbs analyses. This plant can be considered as source of trace elements for people who use it. However the traditional healers recommended the use it with care and always for short treatment periods [35]. It is clear that further experiences are planned to confirm or refute our results obtained by CG/ MS and HPLC for the identification of AAs. In its warning, the FDA recommended that all botanical remedies known or suspected of containing Aristolochic acids be discarded. People should be largely aware of the regulated of some botanical products as dietary supplements by the FDA under the Dietary Supplement Health

Authors are grateful to the National Institute of Forensic Science and Criminology (INCC), Bouchaoui, Algeria for the analysis of our herb by CG/MS

*DOI: http://dx.doi.org/10.5772/intechopen.95298*

**4. Conclusion**

**Acknowledgements**

and HPLC.

**Abbreviations**

## **4. Conclusion**

*Trace Elements and Their Effects on Human Health and Diseases*

*HPLC spectrum analysis of bereztem roots and (AAI) standard. (Sigma A5512–25 mg Yellow powder lot #* 

The Aristolochic acids content of plants varies depending for the same plant species, where it was grown, the time of year, and other factors, that might explain our results? The sample matrix components can influence the limits of detection for Aristolochic acids. We suggested also the insufficient amount of our plant we used 10 mg fine powder of bereztem roots. Although the protocol experimental described by Cherif H.S., and all has been reproduced, in our work, these authors identified the Aristolochic acid (AAI) in the rhizome of bereztem collected in the other city of Algeria: Blida (smell city) located about 47 km in southwest of Algiers. While our plant is collected in the region of Taourirt Aden in (kabylia). Broad range of biological activity of AAs, beneficial as well as adverse effects was reported by Kupchan and Doskotch [33]; therefore it would be interesting to determine the organic composition, it is known that the essential oils contained in the rhizome and aerial part of this herb are mainly responsible for the antimicrobial and cytotoxic effect [34]. And then instead to banned the use of herbal remedy containing acid aristolochic it will be possible to separate the useful from the toxic fractions

**102**

of plant.

**Figure 4.**

*wxbb6331VPCODE)*

Seven elements have been determined in Aristiolochia Longa. L using INAA, technique usually quite for herbs analyses. This plant can be considered as source of trace elements for people who use it. However the traditional healers recommended the use it with care and always for short treatment periods [35]. It is clear that further experiences are planned to confirm or refute our results obtained by CG/ MS and HPLC for the identification of AAs. In its warning, the FDA recommended that all botanical remedies known or suspected of containing Aristolochic acids be discarded. People should be largely aware of the regulated of some botanical products as dietary supplements by the FDA under the Dietary Supplement Health and Education Act (DSHEA) of 1994 (FDA 1995) [36].

## **Acknowledgements**

Authors are grateful to the National Institute of Forensic Science and Criminology (INCC), Bouchaoui, Algeria for the analysis of our herb by CG/MS and HPLC.

## **Abbreviations**


#### **Author details**

Zohra Lamari1 \* and Houria Negache2

1 NUR Reactor Division, Research Department, Nuclear Research Center of Draria, Draria, Algeria

2 Nuclear Applications Division/Medical Applications Department/Nuclear Research Center of Algiers, Algiers, Algeria

\*Address all correspondence to: zahra750@yahoo.com; zohralamari@yahoo.fr

© 2021 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.

**105**

*Analysis of* Aristolochia longa *L. Medicinal Plant from Algeria*

[9] Cherif H.S, F. Said et al. Identification et caracterisation de quelques Composés chimiques chez Aristolochia Longa.nr.3- 4, 2009 p.

[10] Kohara A, Suzuki T, Honma M, Ohwada T, Hayashi M .2002 . Mutagenicity of aristolochic acid in the lambda /lacZ transgenic mouse (Muta TM Mouse). Mutat Res 515 (1-2): 63-72. support not reported. Authors affiliated with National Institute of Health Scioences , Japan ; Nagoya City University , Japan; University of Tokyo,

[11] EMEA.2000. Position paper on the risks associated With the use of herbal products Containing Aristolochia species. European Agency for the Evaluation of the Medicinal Products. http:// www.emea.eu.int/pdfs/humen/ hmpwp/002300en.pdf. Last accessed:

[12] IARC, 2002. Some Traditional Herbal Medicines,Some Mycotoxins, Naphtalene and Styrene , IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans. Vol.82, Lyon , France : International Agency for Research on

[13] PFAF. 2005.Plants for a future Database. Plants for a Future. http:// www.ibiblio.org/pfaf/D|\_search.html.

[14] Jean-pierre Cosyns. Aristolochic Acid-and ochratoxin A-DNA adducts: possible markers of Balkan endemic nephropathy and Associated urotherial

[15] Vanherweghem JL,Depierreux M,

tumors Medicine and Biology Vol.11,N°1.p; 1-4, 2004

Tielemans C , Abramowiez D, Dratwa M, Jadoul M, Richard C, Vandervelde D, Verbeelen D,

71- 72

Japan

3/9/04

Cancer.p.69-128

Last accessed: 5/505

*DOI: http://dx.doi.org/10.5772/intechopen.95298*

[1] Cherif HS, Saidi F, Boutoumi H, Rouibi A, Chaouia C. Identification and characterization of some chemicals from *Aristolochia longa L*. Agricultura

[2] Saidi F, Cherif HS, Lazouri H, Aid K, Rouibi A, Bele C, Matea C. Determination of the lipid compounds of *Aristolochia Longa* L. from Algeria.

[3] Starr F, Starr K, Loope L. 2003. Plants of Hawai'i: *Aristolochia littoralis*. Hawaiian Ecosystems at Risk Project. http://www.hear.org/starr/reports/pdf/ aristolochialittoralis.pdf. Last accessed: 10/19/05. (Support not reported. Authors affiliated with U.S. Geological

[4] Chinese HERBS Nephropathy: *AVariant Form in Japan.* Internal Medecine .2001;Vol.40, No.4 (April

[5] Benzakour G, Benkirane N, Amrani M, Oudghiri M. Immunostimulatory potential of *Aristolochia longa* L. induced toxicity on liver, intestine and kidney in mice. J Toxicol Environ Health Sci

[6] Sithranga Boopathy N, Kathiresan K. Anticancer drugs from marine flora: An overview. J Oncol 2010;2010:214186

[7] Robinson MM, Zhang X. The world medicines situation 2011, traditional medicines: Global situation, issues And challenges. Geneva: World Health

[8] González F, Esquivel HE, Murcia GA and Pabón- Mora N. *Aristolochia pentandra* (Aristolochiaceae) in Colombia: Biogeographic implications and proposed synapomorphies between the pentandrous species of *Aristolochia* and its South American sister group. Rev Aca Colom Cien 2010;34:467-78

Bull U Agr 2009; 66: 17-23

**References**

2009 ; 3:76-82

Survey)

2001).

2011;3:214-22

Organization Press

#### **References**

*Trace Elements and Their Effects on Human Health and Diseases*

**104**

**Author details**

\* and Houria Negache2

Research Center of Algiers, Algiers, Algeria

provided the original work is properly cited.

1 NUR Reactor Division, Research Department, Nuclear Research Center of Draria,

2 Nuclear Applications Division/Medical Applications Department/Nuclear

\*Address all correspondence to: zahra750@yahoo.com; zohralamari@yahoo.fr

© 2021 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,

Zohra Lamari1

Draria, Algeria

[1] Cherif HS, Saidi F, Boutoumi H, Rouibi A, Chaouia C. Identification and characterization of some chemicals from *Aristolochia longa L*. Agricultura 2009 ; 3:76-82

[2] Saidi F, Cherif HS, Lazouri H, Aid K, Rouibi A, Bele C, Matea C. Determination of the lipid compounds of *Aristolochia Longa* L. from Algeria. Bull U Agr 2009; 66: 17-23

[3] Starr F, Starr K, Loope L. 2003. Plants of Hawai'i: *Aristolochia littoralis*. Hawaiian Ecosystems at Risk Project. http://www.hear.org/starr/reports/pdf/ aristolochialittoralis.pdf. Last accessed: 10/19/05. (Support not reported. Authors affiliated with U.S. Geological Survey)

[4] Chinese HERBS Nephropathy: *AVariant Form in Japan.* Internal Medecine .2001;Vol.40, No.4 (April 2001).

[5] Benzakour G, Benkirane N, Amrani M, Oudghiri M. Immunostimulatory potential of *Aristolochia longa* L. induced toxicity on liver, intestine and kidney in mice. J Toxicol Environ Health Sci 2011;3:214-22

[6] Sithranga Boopathy N, Kathiresan K. Anticancer drugs from marine flora: An overview. J Oncol 2010;2010:214186

[7] Robinson MM, Zhang X. The world medicines situation 2011, traditional medicines: Global situation, issues And challenges. Geneva: World Health Organization Press

[8] González F, Esquivel HE, Murcia GA and Pabón- Mora N. *Aristolochia pentandra* (Aristolochiaceae) in Colombia: Biogeographic implications and proposed synapomorphies between the pentandrous species of *Aristolochia* and its South American sister group. Rev Aca Colom Cien 2010;34:467-78

[9] Cherif H.S, F. Said et al. Identification et caracterisation de quelques Composés chimiques chez Aristolochia Longa.nr.3- 4, 2009 p. 71- 72

[10] Kohara A, Suzuki T, Honma M, Ohwada T, Hayashi M .2002 . Mutagenicity of aristolochic acid in the lambda /lacZ transgenic mouse (Muta TM Mouse). Mutat Res 515 (1-2): 63-72. support not reported. Authors affiliated with National Institute of Health Scioences , Japan ; Nagoya City University , Japan; University of Tokyo, Japan

[11] EMEA.2000. Position paper on the risks associated With the use of herbal products Containing Aristolochia species. European Agency for the Evaluation of the Medicinal Products. http:// www.emea.eu.int/pdfs/humen/ hmpwp/002300en.pdf. Last accessed: 3/9/04

[12] IARC, 2002. Some Traditional Herbal Medicines,Some Mycotoxins, Naphtalene and Styrene , IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans. Vol.82, Lyon , France : International Agency for Research on Cancer.p.69-128

[13] PFAF. 2005.Plants for a future Database. Plants for a Future. http:// www.ibiblio.org/pfaf/D|\_search.html. Last accessed: 5/505

[14] Jean-pierre Cosyns. Aristolochic Acid-and ochratoxin A-DNA adducts: possible markers of Balkan endemic nephropathy and Associated urotherial tumors Medicine and Biology Vol.11,N°1.p; 1-4, 2004

[15] Vanherweghem JL,Depierreux M, Tielemans C , Abramowiez D, Dratwa M, Jadoul M, Richard C, Vandervelde D, Verbeelen D,

Vanhaelen-Fastre R, Vanhaelen M.1993. Rapidly progressive interstitial renal fibrosis in young women : association with slimming regimen including Chinese herbs . Lancet 341(8842): 387- 391.(support not reported, Authors affiliated with Université Libre de Bruxelles , Belgium, Vrje Universiteit Brussel, Belgium, Catholique de Louvain , Belgium)

[16] Kupchan SM, Doskotch RW.1962. Tumor inhibitors. I. Aristolochic acid, the active principle of Aristolochic India. Jmed Pharm Chem 91 : 657-659. (Supported by the National Cancer Institute. Authors affiliated with University of Wisconsin)

[17] Jackson I., Kofman S, Weiss A, Brodovsky H.1964, Aristolochic acid ( NSC- 50413): Phase I clinical study. Cancer Chemother Rep 42:35-37. (Support not reported. Authors affiliated with Jefferson Medical College Hospital and Presbyterian. St. Luke's Hospital, USA)

[18] Mix DB, Guinaudeau H,Shamma M. 1982. The aristolochic acids and aristolactams. JNat Prod 45(6): 657- 666.( Support not reported Authors affiliated with Pennsylvania state University , PA; Universite de Limoges, France; Centre d'Etudes Pharmaceutiques, France)

[19] Kumar V , Poonam, Prasad AK , Parmar VS.2003. Naturally occuring aristolactams ,aristolochic acids and dioxoporphines and their biological activities. Nat P rod Rep 20(6): 565-583. (Supported by the Council of Scientific and Industrial Research. Authors affiliated with University of Delhi, India)

[20] Arlt VM, Stiborova M, Schmeiser HH .2002. Aristolochic acid as a probable human cancer hazard in Herbal remedies : A review. Mutagenesis, 17(4): 265-277

[21] Hashimoto K, Higuchi M, Makino B, Sakakibara I, Kubo M, Komatsu Y, Maruno M, Okada M.1999. Quantitative analysis of aristolochic acids, toxic compounds, contained in some medicinal plants. J E thnopharm 64: 185-189. (Support not reported. Authors affiliated with Tsumara and C company, Japan; Toyama Medical and Pharmaceutical University, Japan.)

[22] Kite GC, Yule MA, Leon C, Simmonds MS.2002. Detecting aristolochic acids in herbal remedies by lquid chromatography/serial mass spectrometry. Rapid Commun Mass Spectrom 16(6): 585-590 (support not reported. Authors affiliated with Royal Botanic Gardens, UK and University of Greenwich, UK.)

[23] IARC, 2002. Some Traditional Herbs Medicines , Some Mycotoxins, Naphtalene and Styrene, IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans .vol.82,Lyon, France International Agency for Research on Cancer .p.69 -128

[24] Grollman AP, Jelacovie B.2007. Role of environnemental toxins in endemic (Balkan) nephropathy. October .2006, Zagreb, Crotia. J Am Soc Nephrol 18(11): 2817-23.(Supported by NIEHS, Fogarty International Center and the Croation Ministries of Science and Health Authors affiliated with stony Brook University , NY; Zagreb University School of Medicine and University Hospital Center, Croatia)

[25] Pozdzik AA, Berton A, Schmeiser HH, Missoum W, Decaestecker C, Salmon IJ, Vanherweghem JL, Nortier JL .2010; Aristolochic acid nephropathy revisited: A Place for innate and adaptive immunity? Histopathol., 56(4): 449-463.

[26] Mengs U.1987. Acute toxicity of aristolochic acid in redents. Aech Toxicol59 (5): 328-333(Support not

**107**

*Analysis of* Aristolochia longa *L. Medicinal Plant from Algeria*

and cytotoxicity of essential oils From Aristolochia mollissima. Environmental Toxicology and Pharmacology 23.2007;

[35] Benchaabane A, Abbad A .1997. Medicinal Plants marked in Marrakech. Trace of the Present. Marrakech, p. 74

[36] FDA.1995. Dietary Supplement Health and Education Act of 1994. U.S.Food and Drug Administration. http://www.cfsan.fda.gov/dms/ dietsupp.html Last accessed: 7/1/06

p. 162- 167

*DOI: http://dx.doi.org/10.5772/intechopen.95298*

reported. Authors affiliated with Dr. Madaus Gmbh & Co., Germany)

[27] U.S.National library of Medicine –

[28] Mengs U, Stotzem CD .1993. Renal toxicity of aristolochic acid in rats as an example of nephrotoxicity testing in routine toxicology. Arch. Toxicol., 67:

[29] Chung-Hsin Chen et al . Aristolochic acid – associated urotherial cancer in Taiwan PNAS /may 221,2012 /vol 109 /

[30] U.S. Department of Health and Human Services Public Health Services National Toxicology Program Research Triangle Park, NC 27709: final Report on Carcinogens Background Document for Aristolochic Acids September 2,

[31] Flurer RA,Jones MB, Vela N, Ciolino LA, Wolnick KA.2001. Determination of Aristolochic Acid in Traditional Chines Medicines and Dietary Supplements , DFS/ORO/ ORA NO.4212. U.S. Food and Drug

Administration 13 pp.

University, Japan.)

[32] Tanaka A,Nishida R,

Yoshida T, Koshikawa M, Goto M, Kuwahara T.2001. Outbreak of Chinese Herb nephropathy in Japan: are thre any differences from Belgium ? Intern Med 40(4): 296- 300.(Support not reported . Authors affiliated With Osaka Saiseikai Nakatsu Hospital, Japan; Kyoto

[33] Kupchan SM, Doskotch RW.1962. Tumor inhibitors. I. Aristolochic acid, the active principle of Aristolochia indica. JMed Pharm Chem91: 657-659. (Supported by the National Cancer Institute. Authors affiliated with University of Wisconsin.)

[34] Jian Qing Yu, Zhi Xiong Liao et al. Composition, Antimicrobial activity

Bethesda MD August7, 2013

307- 311.

2008

n° 21 /8241- 8246

*Analysis of* Aristolochia longa *L. Medicinal Plant from Algeria DOI: http://dx.doi.org/10.5772/intechopen.95298*

reported. Authors affiliated with Dr. Madaus Gmbh & Co., Germany)

*Trace Elements and Their Effects on Human Health and Diseases*

[21] Hashimoto K, Higuchi M, Makino B, Sakakibara I, Kubo M, Komatsu Y, Maruno M, Okada M.1999. Quantitative analysis of aristolochic acids, toxic compounds, contained in some medicinal plants. J E thnopharm 64: 185-189. (Support not reported. Authors affiliated with Tsumara and C company, Japan; Toyama Medical and Pharmaceutical University, Japan.)

[22] Kite GC, Yule MA, Leon C, Simmonds MS.2002. Detecting aristolochic acids in herbal remedies by lquid chromatography/serial mass spectrometry. Rapid Commun Mass Spectrom 16(6): 585-590 (support not reported. Authors affiliated with Royal Botanic Gardens, UK and University of

[23] IARC, 2002. Some Traditional Herbs Medicines , Some Mycotoxins, Naphtalene and Styrene, IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans .vol.82,Lyon, France International Agency for Research on

[24] Grollman AP, Jelacovie B.2007. Role of environnemental toxins in endemic (Balkan) nephropathy. October .2006, Zagreb, Crotia. J Am Soc Nephrol 18(11): 2817-23.(Supported by NIEHS, Fogarty International Center and the Croation Ministries of Science and Health Authors affiliated with stony Brook University , NY; Zagreb University School of Medicine and University Hospital Center, Croatia)

[25] Pozdzik AA, Berton A, Schmeiser HH, Missoum W, Decaestecker C, Salmon IJ, Vanherweghem JL, Nortier JL .2010; Aristolochic acid nephropathy revisited:

A Place for innate and adaptive immunity? Histopathol., 56(4):

[26] Mengs U.1987. Acute toxicity of aristolochic acid in redents. Aech Toxicol59 (5): 328-333(Support not

449-463.

Greenwich, UK.)

Cancer .p.69 -128

Vanhaelen-Fastre R, Vanhaelen M.1993. Rapidly progressive interstitial renal fibrosis in young women : association with slimming regimen including Chinese herbs . Lancet 341(8842): 387- 391.(support not reported, Authors affiliated with Université Libre de Bruxelles , Belgium, Vrje Universiteit Brussel, Belgium, Catholique de

[16] Kupchan SM, Doskotch RW.1962. Tumor inhibitors. I. Aristolochic acid, the active principle of Aristolochic India. Jmed Pharm Chem 91 : 657-659. (Supported by the National Cancer Institute. Authors affiliated with

Louvain , Belgium)

University of Wisconsin)

Hospital, USA)

[17] Jackson I., Kofman S, Weiss A, Brodovsky H.1964, Aristolochic acid ( NSC- 50413): Phase I clinical study. Cancer Chemother Rep 42:35-37. (Support not reported. Authors

affiliated with Jefferson Medical College Hospital and Presbyterian. St. Luke's

[18] Mix DB, Guinaudeau H,Shamma M.

1982. The aristolochic acids and aristolactams. JNat Prod 45(6): 657- 666.( Support not reported Authors affiliated with Pennsylvania state University , PA; Universite de Limoges, France; Centre d'Etudes

Pharmaceutiques, France)

[19] Kumar V , Poonam, Prasad AK , Parmar VS.2003. Naturally occuring aristolactams ,aristolochic acids and dioxoporphines and their biological activities. Nat P rod Rep 20(6): 565-583. (Supported by the Council of Scientific and Industrial Research. Authors affiliated with University of Delhi,

[20] Arlt VM, Stiborova M, Schmeiser HH .2002. Aristolochic acid as a probable human cancer hazard in Herbal remedies : A review. Mutagenesis, 17(4): 265-277

**106**

India)

[27] U.S.National library of Medicine – Bethesda MD August7, 2013

[28] Mengs U, Stotzem CD .1993. Renal toxicity of aristolochic acid in rats as an example of nephrotoxicity testing in routine toxicology. Arch. Toxicol., 67: 307- 311.

[29] Chung-Hsin Chen et al . Aristolochic acid – associated urotherial cancer in Taiwan PNAS /may 221,2012 /vol 109 / n° 21 /8241- 8246

[30] U.S. Department of Health and Human Services Public Health Services National Toxicology Program Research Triangle Park, NC 27709: final Report on Carcinogens Background Document for Aristolochic Acids September 2, 2008

[31] Flurer RA,Jones MB, Vela N, Ciolino LA, Wolnick KA.2001. Determination of Aristolochic Acid in Traditional Chines Medicines and Dietary Supplements , DFS/ORO/ ORA NO.4212. U.S. Food and Drug Administration 13 pp.

[32] Tanaka A,Nishida R, Yoshida T, Koshikawa M, Goto M, Kuwahara T.2001. Outbreak of Chinese Herb nephropathy in Japan: are thre any differences from Belgium ? Intern Med 40(4): 296- 300.(Support not reported . Authors affiliated With Osaka Saiseikai Nakatsu Hospital, Japan; Kyoto University, Japan.)

[33] Kupchan SM, Doskotch RW.1962. Tumor inhibitors. I. Aristolochic acid, the active principle of Aristolochia indica. JMed Pharm Chem91: 657-659. (Supported by the National Cancer Institute. Authors affiliated with University of Wisconsin.)

[34] Jian Qing Yu, Zhi Xiong Liao et al. Composition, Antimicrobial activity

and cytotoxicity of essential oils From Aristolochia mollissima. Environmental Toxicology and Pharmacology 23.2007; p. 162- 167

[35] Benchaabane A, Abbad A .1997. Medicinal Plants marked in Marrakech. Trace of the Present. Marrakech, p. 74

[36] FDA.1995. Dietary Supplement Health and Education Act of 1994. U.S.Food and Drug Administration. http://www.cfsan.fda.gov/dms/ dietsupp.html Last accessed: 7/1/06

## *Edited by Daisy Joseph*

This book is an excellent compilation of trace elements and their positive and negative effects on human health and the environment. Over two sections, the book examines the adverse effects of trace elements in the human body and the atmosphere and how to overcome them.

Published in London, UK © 2021 IntechOpen © Navapon\_Plodprong / iStock

Trace Elements and Their Effects on Human Health and Diseases

Trace Elements and Their

Effects on Human Health and

Diseases

*Edited by Daisy Joseph*