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العنوان
Determination of urainary polycyclic aromatic hydrocarbon metabolites as biomarkers of exposure to environmental marine pollution =
المؤلف
Khamis, Mahmoud Abdel Hamid.
هيئة الاعداد
باحث / Mahmoud Abdel Hamid Khamis
مشرف / Aziza Abdel Azem Ibrahim
مشرف / Ahmed Moustafa Hassan El Nemr
مشرف / El Hassan Mostafa Gaber Mokher
الموضوع
Applied Medical Chemistry.
تاريخ النشر
2013.
عدد الصفحات
133 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
الطب
تاريخ الإجازة
6/4/2013
مكان الإجازة
جامعة الاسكندريه - معهد البحوث الطبية - Applied Medical Chemistry
الفهرس
Only 14 pages are availabe for public view

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from 86

Abstract

Polycyclic aromatic hydrocarbon (PAHs) compounds are persistent organic pollutants of high environmental concern with known carcinogenic activity, they are launched in the environment through industrial effluents, urban residues, land runoff, discarding of oil and for the combustion of fossil fuels and biomass. They are generally more resistant to biodegradation than many saturated biomarkers and tend to persist in contaminated sediments, water, soil, atmospheric particulate matter and some organisms such as mussels.
Bivalves have been extensively used as sentinel organisms of marine pollution and are considered the best aquatic organisms for monitoring the PAH bioaccumulation in estuarine ecosystems, being used in programs of monitoring the quality of the water. Thus the objectives of the present study are to assess the occurrence and distribution of PAHs in mussels of Boughaz El-Maadiya, to identify the origin of PAHs in the Boughaz El-Maadiya, and conduct an environmental risk assessment to evaluate the possibility of occurrence of adverse ecological effects to benthic species due to the exposure to PAHs concentrated in the Boughaz El-Maadiya sediments.
In this context, the results of the present study demonstrated that the full range (2-6 rings) of PAHs were detected in the mussel tissues. With regard to benzo[a]pyrene (BaP), which represent the most potentially carcinogenic PAH, European Regulation 1881/2006/EC fixed at 10 µg kg−1 of wet weight the MRL (maximum residual level) in bivalves mollusks. However, the results of the present study proved that the concentration of BaP ranged from 20 µg/kg to 970 µg/kg wet weight higher about 100 time more than the MRL (10 µg/kg wet weight), since these marine invertebrates showed values higher 100 time than the cited MRL, that supposed to be a big risk for human health.
The present study was conducted on 70 subjects which they divided into four groups:
ii) Group І : Consisted of 12 nonsmokers control subjects.
iii) Group II : Included 22 non smokers fishermen subjects.
iv) Group III: Comprised of 10 smokers control subjects.
v) Group ІV: Contained 26 smokers fishermen subjects
The present results revealed that, there were a highly significant increase in the level of urinary 1-hydroxypyrene and α-naphthol level of fishermen group when compared with that of control group. Meanwhile statistical analysis between groups emphasized that there were a sharply significant increase in the level of urinary 1-hydroxypyrene and α-naphthol in group II, III, ІV when compared with that of group I.
Several studies have demonstrated that urinary 1-OHP is an appropriate marker for PAH exposure in different working environment. The urinary 1-OHP was a solid biological exposure indicator in assessing occupational exposure to PAHs. Knowing the low cost level for large-scale application of the test, 1-OHP is the preferred biomarker for routine exposure assessment of workers and for PAH exposure in the environmental exposure assessment of healthy human populations.
1-OHP is the principal metabolite of the four-ring PAH pyrene, representing 90% of the urinary excretion of pyrene in humans. The measurement of urinary 1-OHP has been used in various epidemiologic studies investigating PAH exposure from tobacco smoke, traffic air pollution, and occupational sources. It is well known that cigarette smoke contains a variety of potentially toxic components including PAHs. Pyrene from smoking is presumably the main source of 1-hydroxypyrene detected in the cigarette smokers’ urine, particularly when compared with non-cigarette smokers.
Urinary 1- naphthol, recently have been suggested as route-specific biomarkers for exposure to airborne polycyclic aromatic hydrocarbons. The results of the present study confirms the findings of earlier studies which demonstrated that smoking of cigarette significantly increases the urinary 1-OHP as well as 1-naphthol concentration. Since the present study revealed that the level of either 1-OHP or 1-naphthol were more or less amounted in the two groups either smokers control or nonsmokers fishermen. Then, the increase urinary 1-OHP and 1-naphthol excretion in smokers could be explained by the fact that cigarette smoke contains a wide variety of toxic xenobiotics including PAHs.
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental carcinogens and metabolized by a variety of xenobiotic-metabolizing enzymes . These enzymes mainly participate in the conversion of PAHs to more polar and water-soluble metabolites, and the resultant metabolites are readily excreted from the body. However, during the course of metabolism, a variety of unstable and reactive intermediates of PAHs are formed, and these metabolites attack DNA, causing cell toxicity and transformation. P450s and epoxide hydrolase convert PAHs to proximate carcinogenic metabolites, PAH-diols, and these products are further metabolized by P450s to ultimate carcinogenic metabolites, PAH diol-epoxides, or by aldo-keto reductase to reactive PAH o-quinones.
The toxicity of quinones may be related not only to reactive oxygen species (ROS) such as, superoxide anion radicals (O2) and hydrogen peroxide (H2O2),but also to that of semiquinone radicals. Quinones are also electrophilic and therefore may covalently bind to cellular nucleophiles, such as proteins and nucleic acids.
The data of the present study revealed that there was a highly significantly elevated levels of malondialdehyde in sera of two fishermen groups (II, ІV) as well as smokers control group (group III) than that the nonsmokers control group (group I). Which reflects the fact that fishermen groups (II, ІV) and smokers control (group I) definitely suffer from oxidative stress. Increasing evidence suggests that oxidative stress is also of ecological significance, particularly in the aquatic environment which provides a sink for many pollutants capable of causing oxidative stress. Moreover, cigarette smoking is an additive risk factors to induce more oxidative stressors.
It is worth to noted that oxidative stress is accompanied with disturbance of antioxidant defense system. These findings were cast light and represented good interpretation of present results which elucidated that there were highly significant decrease in the level of whole blood glutathione and the enzymatic activity levels of Catalase and superoxide dismutase of smoker control (group III) as well as two fishermen groups (group II and ІV) than that of nonsmoker control group(group I). While the enzymatic activity glutathione-s-transferase (GST) was significant increase in groups II, III, ІV when compared with that of group І. At the same time the enzymatic activity of glutathione peroxidase was significantly more elevated in fishermen group when compared with that of control group.
Conclusively:
Polycyclic aromatic hydrocarbons (PAHs) are one of the most important classes of ubiquitous priority pollutants whose carcinogenic and mutagenic properties and endocrine disrupting effects have been reported. Both natural and anthropogenic sources account for their diffusion in the environment, as a consequence of atmospheric transport, deposition and dispersion in the environment.
An important and very extensively studied prototype of this environmental contaminant is benzo(a)pyrene (BaP). The adverse effects produced by BaP are linked to the cytosolic aryl hydrocarbon receptor (AhR), a ligand dependent basic helix–loop–helix transcription factor. When the ligand BaP binds to AhR, it translocates into the nucleus, associated with AhR nuclear translocator (ARNT) and reacts with xenobiotic responsive elements (XRE) found in the 5’ flanking regions of responsive genes . In this way, AhR is notably implicated in upregulation of drug-metabolizing enzymes such as cytochromes P450 (CYPs), especially CYP1A1.
BaP is metabolized by CYP1A1 in mammalian tissues to various oxides, phenols, trans-dihydrodiols, and further activated to electrophilic intermediates that bind to DNA and induces mutagenic, cytotoxic, and teratogenic effects in various tissues. The toxic effects of BaP are also exacerbated by peroxidases which metabolize BaP into benzo(a)pyrene Quinones (BPQ). These BPQs could directly form ROS through redox cycling or disrupt mitochondrial electron transport, leading to more ROS formation and depletion of ATP.
Several reports identify certain PAHs which clearly resemble steroid hormones as example of environmental estrogens and human exposure to non-steroidal environmental estrogens is thought to be a risk factor for endocrine disruption and development of cancer.
Among the PAH metabolites associated with idiopathic male infertility in a study, 1-OHP is the main and general metabolite of pyrene and is one of the PAH metabolites with the highest measured levels in human urine. It was suggested that 1-OHP may affect male infertility and alter semen quality even at non-occupational exposure levels, which is consistent with a human study and in vivo studies. The structure of PAHs (some regions and carbon atom positions) determine their biological activity, and the peri-condensed structure of 1-OHP may contribute to its independent effect.
A number of biological mechanisms may contribute to the relationship was observed between PAH exposure and male infertility through altered semen quality. Some studies have suggested that PAHs and their metabolites may be hormonally active. Animal studies have reported associations between PAH exposures and daily sperm production, sperm motility and sperm abnormalities, while human data have suggested that PAHs are associated with sperm dysfunction including abnormal sperm morphology, decreased sperm motility and sperm DNA damage.
Furthermore, PAHs have been shown to cross the placenta and form hemoglobin adducts in both maternal and fetal sera, in addition to forming DNA adducts in both human and murine trophoblast cells. Experimental animal studies have demonstrated that benzo(a)pyrene (BaP), a representative PAH, is a reproductive toxicant and produces a variety of neurodevelopmental effects including impairment of memory and ability to learn, consistent with observed alterations in the expression of key genes involved in long-term potentiation.
The release of toxic chemicals from point and nonpoint sources leads to the contamination of surface water and sediments of streams, rivers, and lakes. The fat-soluble environmental contaminants concentrate in fatty tissues of fish by bioaccumulation and biomagnifications processes. Thus, high levels of environmental contaminants may be stored in fatty tissues of fish, Potential health risks related to fish consumption may be due to the contamination of fish with carcinogenic and non-carcinogenic environmental contaminants.
The potential health benefits related to fish consumption are due to the presence of proteins, unsaturated essential fatty acids, minerals, and vitamins. Additional health benefits from the consumption of fish or fish oil may be related to polyunsaturated fatty acids (PUFAs) especially omega-3 PUFAs. Scientific data indicated that the consumption of fish or fish oil containing omega-3 PUFAs reduces the risk of coronary heart disease, decreases mild hypertension, prevents certain cardiac arrhythmias, and sudden death, lowers the incidence of diabetes, and appears to alleviate symptoms of rheumatoid arthritis. It appears that omega-3 PUFAs play a vital role in the development and function of the nervous system (brain), photoreception (vision), and the reproductive system.
There are several natural compounds that participate in the antioxidative defense mechanism of fish. These include enzymes (catalase, peroxidase, glutathione and superoxide dismutase), carotenoids, peptides, amino acids and phenolic compounds (tocopherols, ubiquinones). These compounds are found in the cell plasma, mitochondria of cell membranes.
The health benefits of fish and seafood have been well documented and widely promoted in recent years. Fish is low in saturated fat and is a healthy alternative to red meat. It provides the body with essential vitamins and minerals, including iron; zinc (from shellfish); vitamins A, B and D; and, of course, protein. Omega-3 fatty acids found in fish are also beneficial, particularly in terms of cardiovascular health. Preliminary evidence suggests that early exposure to omega-3 fats may enhance brain development as also protect the liver from steatosis because fish and sea food have high lipotropic effects.