Modulation of the endogenous antioxidants paraoxonase-1 and urate by pesticide exposure and genetic variants of xenobiotic-metabolizing enzymes

Abstract

This study evaluated the association between pesticide exposure in farmworkers and plasma levels of the endogenous antioxidants urate and paraoxonase-1 (PON1) enzyme activities (paraoxonase, arylesterase and diazoxonase, three substrate-specific assays for measuring PON1 function) by using generalized estimating equations (GEEs). Decreases in plasma and erythrocyte cholinesterases (BChE and AChE, respectively) were used as biomarkers of pesticide exposure. We also assessed the contribution of genetic polymorphisms of the pesticide-metabolising enzymes PON1, glutathione S-transferases (GST) and cholinesterase variants (BCHE) on plasma levels of endogenous antioxidants and potential gene-environment interactions. A dual effect was observed on paraoxonase depending on the pattern of pesticide exposure. Thus, exposure to anticholinesterase pesticides was associated with decreased paraoxonase activity and urate levels whereas long-term pesticide exposure showed an association with increased paraoxonase activity. Significant interactions were observed between BChE activity and PON1 regulatory region polymorphisms on arylesterase and diazoxonase activities, and between AChE activity (a biomarker for long-term pesticide exposure) and PON1192RR genotype on arylesterase activity. These findings suggest that pesticide exposure may affect plasma antioxidant potential and that relevant gene-pesticide interactions may play a mechanistic role in oxidative stress-induced diseases following pesticide exposure. Nonetheless, more studies are needed to better characterise these interactions.