title: 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.
authors.affiliation: Department of Legal Medicine and Toxicology, University of Granada School of Medicine, Granada, Spain. Electronic address: ajerez@ugr.es.
authors.forename: Antonio F
authors.initials: AF
authors.lastname: Hernández
authors.forename: Fernando
authors.initials: F
authors.lastname: Gil
authors.forename: Marina
authors.initials: M
authors.lastname: Lacasaña
authors.forename: Miguel
authors.initials: M
authors.lastname: Rodríguez-Barranco
authors.forename: Antonio
authors.initials: A
authors.lastname: Gómez-Martin
authors.forename: David
authors.initials: D
authors.lastname: Lozano
authors.forename: Antonio
authors.initials: A
authors.lastname: Pla
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000383:Agriculture; D043303:Aryldialkylphosphatase / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D059647:Gene-Environment Interaction; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects; D010575:Pesticides / Q000633:toxicity*; D020641:Polymorphism, Single Nucleotide; D014527:Uric Acid / Q000097:blood*; D055815:Young Adult
chemical_list: D000110:Acetylcholinesterase; D043303:Aryldialkylphosphatase; D005982:Glutathione Transferase; D010575:Pesticides; D014527:Uric Acid; C413545:glutathione S-transferase T1; C468406:PON1 protein, human
keywords: Cholinesterases; Endogenous antioxidants; Occupational health; Pesticide exposure; Pesticidemetabolising gene variants