(1) Background: Organophosphorus pesticides (OPPs) are major chemicals used in agriculture for eradication of insecticides/pesticides. Unfortunately, the longtime exposure of human beings to OPPs could lead to metabolic disorder such as high blood pressure, hyperglycemia, overweight or dyslipidemia. The aim of this research is to evaluate the possible metabolic dysregulations as a consequence of chronic OPPs exposure to individuals in Cameroon and Pakistan. (2) Methods: Blood samples were collected from 300 participants in each country, into ethylenediaminetetraacetic acid (EDTA) tubes. The samples were extracted with solid phase extraction (methanol/water) for analysis of OPPs with gas chromatography mass spectrometry. The spectrophotometry and Enzyme Linked ImmunoSorbent Assay (ELISA) were used to measure the hepatic, renal, pancreatic and cardiovascular functions. The atherogenic index (AI) was also determined in OPPs exposed and nonexposed cohorts. (3) Results: The results showed the presence of malathion, parathion and chlorpyrifos OPPs residues in Cameroonians, and malathion and chlorpyrifos in Pakistani samples, respectively. Elevated Body Mass Index (BMI), insulin, blood glucose, dyslipidemia and hypertension were noted in OPPs chronic exposed groups. In addition, dysregulated liver and kidney function profiles were observed in all participants regardless of gender and age groups. (4) Conclusions: The study concludes that both the study cohorts showed several metabolic dysregulations attributable to chronic exposure to a mixture of OPPs which may provide precursors for establishment of metabolic syndrome and other chronic diseases. Further different extended population-based studies are suggested to understand the differential metabolic dysfunctions caused by structurally different OPPs mixtures exposure.
- MeSH
- insekticidy * MeSH
- lidé MeSH
- organofosforové sloučeniny MeSH
- pesticidy * toxicita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Kamerun MeSH
- Pákistán MeSH
BACKGROUND AND OBJECTIVES: Organophosphate (OPs) anticholinesterases are one of the main groups of pesticides used in agriculture. Harmful effects of OPs on health have been attributed primarily for irreversible inhibition of acetylcholinesterase (AChE) at nerve synapse. However, studies have shown that inhibition of AChE alone cannot explain all the maladies encountered in prolonged exposure to OPs. Predisposition to population heterogeneity and irregularities in various biochemicals like paraoxonases and inflammatory biochemicals are the possible affects of OPs long term exposure that may lead to sequels of diseases and are less addressed in literature. The study was aimed to assess the cholinergic enzymes (AChE and BChE), PON1, and inflammatory markers (IL1β, IL6, TNFα, CRP, Apo AI, Apo B) and determine the toxicogenetics association of PON1 gene (rs 662 and rs 85456) to chronically OPs exposed groups from Pakistan and Cameroon. MATERIALS AND METHODS: AChE, BChE and PON1 were measured by colorimetric method using spectrophotometry. Inflammatory markers were determined by Elisa assay. PCR-restriction fragment length polymorphism (PCR-RFLP) using salting out method was employed for SNP genotyping. RESULTS: The results revealed the significant (p ≤ 0.05) inhibition of cholinergic enzymes PON 1 was found to be 6.91 ng/mL±1.03 and 2.84 ng/mL±1.40 (mean ± SD) in Pakistan and Cameroon groups respectively. IL6, TNFα, CRP were increased and Apo AI was less while Apo B was increased in OP exposed groups in both population groups. SNPs analysis of PON1 showed significant differences in allelic and genotype frequencies of OPs exposed and non-exposed groups. CONCLUSIONS: PON1 was noticeably less in Cameroonian than Pakistani, albeit both groups have significant decrease in PON1 actity. In addition, the study concludes that OPs induce low grade inflammation, an aetiology of many diseases. Selected PON1 SNPs analysis showed a significant toxicogenetics association with OPs exposure marker enzymes. The results of this study may help in regulation of usage of OPs anticholinesterases in different populations. The study will further open new avenues in toxicogenetic and exploration of SNPs based strategies on organophosphate intoxication.
- MeSH
- acetylcholinesterasa genetika MeSH
- aryldialkylfosfatasa genetika MeSH
- lidé MeSH
- organofosfáty MeSH
- organofosforové sloučeniny * MeSH
- pesticidy * toxicita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Pákistán MeSH
The detrimental effects of organophosphates (OPs) on human health are thought to be of systemic, i.e., irreversible inhibition of acetylcholinesterase (AChE) at nerve synapses. However, several studies have shown that AChE inhibition alone cannot explain all the toxicological manifestations in prolonged exposure to OPs. The present study aimed to assess the status of antioxidants malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) (reduced), catalase, and ferric reducing antioxidant power (FRAP) in chronic OP-exposed groups from Cameroon and Pakistan. Molecular analysis of genetic polymorphisms (SNPs) of glutathione transferases (GSTM1, GSTP1, GSTT1), catalase gene (CAT, rs7943316), sirtuin 1 gene (SIRT1, rs10823108), acetylcholinesterase gene (ACHE, rs2571598), and butyrylcholinesterase gene (BCHE, rs3495) were screened in the OP-exposed individuals to find the possible causative association with oxidative stress and toxicity. Cholinesterase and antioxidant activities were measured by colorimetric methods using a spectrophotometer. Salting-out method was employed for DNA extraction from blood followed by restriction fragment length polymorphism (RFLP) for molecular analysis. Cholinergic enzymes were significantly decreased in OP-exposed groups. Catalase and SOD were decreased and MDA and FRAP were increased in OP-exposed groups compared to unexposed groups in both groups. GSH was decreased only in Pakistani OPs-exposed group. Molecular analysis of ACHE, BCHE, Catalase, GSTP1, and GSTM1 SNPs revealed a tentative association with their phenotypic expression that is level of antioxidant and cholinergic enzymes. The study concludes that chronic OPs exposure induces oxidative stress which is associated with the related SNP polymorphism. The toxicogenetics of understudied SNPs were examined for the first time to our understanding. The findings may lead to a newer area of investigation on OPs induced health issues and toxicogenetics.
- MeSH
- acetylcholinesterasa genetika MeSH
- butyrylcholinesterasa genetika MeSH
- dospělí MeSH
- glutathion-S-transferasa fí genetika MeSH
- glutathion MeSH
- glutathiontransferasa genetika MeSH
- GPI-vázané proteiny genetika MeSH
- interakce genů a prostředí * MeSH
- jednonukleotidový polymorfismus * MeSH
- katalasa genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- malondialdehyd MeSH
- mladiství MeSH
- mladý dospělý MeSH
- organofosforové sloučeniny škodlivé účinky MeSH
- oxidační stres genetika MeSH
- sirtuin 1 genetika MeSH
- vystavení vlivu životního prostředí škodlivé účinky analýza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Kamerun MeSH
- Pákistán MeSH
