Oxidative Stress and Analysis of Selected SNPs of ACHE (rs 2571598), BCHE (rs 3495), CAT (rs 7943316), SIRT1 (rs 10823108), GSTP1 (rs 1695), and Gene GSTM1, GSTT1 in Chronic Organophosphates Exposed Groups from Cameroon and Pakistan.

Leonel Javeres Mbah Ntepe,Saqlain Raza,Syed Muhammad Nurulain,Sajida Batool,Rabia Habib,Ngondi Judith Laure,Kamil Kuca,Eugenie Nepovimova

doi:10.3390/ijms21176432

Abstract

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.

Highlights

Pesticides are an important class of environmental chemical pollutants
Our results indicate that chronic exposure of OPs pesticides can lead to an imbalance in antioxidant enzymes
We identified that in general, there are relevant overlapping effects, for example, cholinergic enzymes (AChE and BChE) and antioxidant enzymes were significantly associated with each of the SNPs studied

Summary

Introduction

Pesticides are an important class of environmental chemical pollutants Their steady and continuous use for more than half a century has become a major public health problem, killing at least 250,000–370,000 people every year [1]. Several toxicological and epidemiological studies far have shown that OPs can induce oxidative stress (OS) by increasing reactive oxygen species (ROS) and reactive nitrogen species (RNS). These reactive oxygen and nitrogen intermediates can react with biological macromolecules altering their physiological functions [13,14,15]. FR can cause genotoxicity by lipid peroxidation which leads to chromosomal breaks, single-stranded DNA breaks with serious consequences on replication or transmission of a genetic message and proteins synthesis [19,20]

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Conclusion