title: Differential modulation of xenobiotic-metabolizing enzymes in rats following single and concurrent exposure to chlorpyrifos, arsenic, and ascorbic acid.
abstract: The present study was undertaken to evaluate the subacute toxicity of arsenic (As) and chlorpyrifos (CPF) alone or in combination. In addition, the ameliorative effect of ascorbic acid on As and/or CPF-induced hepatic microsomal xenobiotic metabolizing enzymes in rats was examined. Rats were divided into 9 groups of 6 animals each: control (deionized water), vehicle control (groundnut oil), ascorbic acid (100 mg/kg body weight), As (40 ppm in water), CPF (5 mg/kg body weight), As (40 ppm) + CPF (5 mg/kg body weight), As + ascorbic acid, CPF + ascorbic acid, and As + CPF + ascorbic acid. After 28 d of exposure, rats were sacrificed and liver was extracted for isolation of hepatic microsomes. Exposure to As or CPF alone as well as both of these in combination significantly altered microsomal proteins and activity of phase I and phase II xenobiotic-metabolizing enzymes. Cytochrome P-450 and cytochrome b 5 levels and activities of aniline p-hydroxylase (APH) and uridine diphosphate glucuronosyltransferase (UGT) were significantly decreased in groups treated with As, CPF, and As plus CPF, while glutathione S-transferase (GST) was not markedly altered. Enzymatic activity of aminopyrine N-demethylase (ANDM) was also significantly reduced in As- and CPF-only groups. Co-administration of ascorbic acid effectively countered the As- and CPF-induced alterations in xenobiotic-metabolizing enzymes.
authors.affiliation: a Department of Pharmacology and Toxicology , College of Veterinary Science and Animal Husbandry, U. P. Pt. Deen Dayal Upadhyaya Veterinary and Animal Sciences University (DUVASU) , Mathura , India.
authors.forename: Dinesh Singh
authors.initials: DS
authors.lastname: Rajpoot
authors.forename: Atul
authors.initials: A
authors.lastname: Prakash
authors.forename: Rajesh
authors.initials: R
authors.lastname: Mandil
authors.forename: Anu
authors.initials: A
authors.lastname: Rahal
authors.forename: Satish Kumar
authors.initials: SK
authors.lastname: Garg
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001151:Arsenic / Q000633:toxicity*; D001205:Ascorbic Acid / Q000494:pharmacology*; D004390:Chlorpyrifos / Q000633:toxicity*; D060766:Drinking Water / Q000032:analysis; D007306:Insecticides / Q000633:toxicity; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D059551:Toxicity Tests, Subacute; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D060766:Drinking Water; D007306:Insecticides; D014874:Water Pollutants, Chemical; D004390:Chlorpyrifos; D001151:Arsenic; D001205:Ascorbic Acid