Effect of phenobarbitone on cytochrome P450 activity and chlorpyrifos and 3,5,6-trichloropyridinol levels in liver and serum in rat.
Chlorpyrifos [O,O'-diethyl-O-(3,5,6-trichloro-2-pyridyl) phosphorothionate, CPF] undergoes oxidative desulfuration or dearylation by hepatic microsomal cytochrome P450 (CYP)-mediated monooxygenase reaction to CPF oxon or desethyl CPF, which are further metabolized to 3,5,6-trichloropyridinol (TCP). The present study showed that CPF exposure caused induction of hepatic CYP levels in rats. Phenobarbitone (PB) treatment elevated CYP activity by about 2.2-folds in controls, while CPF exposure to PB-treated rats did not cause further elevation in CYP levels. The levels of CPF in liver tissue and serum of rats given 50 and 100 mg CPF/kg body wt for 3 weeks were 17.15 ng and 29.39 ng/g and 33.71 ng and 56.34 ng/ml, respectively. The levels of TCP in these rats were 123.58 ng and 215.26 ng/g in liver tissue and 391.73 ng and 599.32 ng/ml in serum respectively. On PB-treatment, CPF levels were decreased by 46% and 38% in liver and 23% and 20% in serum of rats receiving 50 mg and 100 mg CPF/kg body wt for 3 days, while TCP levels were increased by 6% and 22% in liver and 22% and 44% serum, respectively. Results of this study clearly show that CYP2B, the PB-inducible form can biotransform CPF faster into TCP.
School of Studies in Biochemistry, Jiwaji University, Gwalior 474 011, India.
Radhey S
RS
Verma
Anugya
A
Mehta
N
N
Srivastava
D000818:Animals; D001711:Biotransformation; D004390:Chlorpyrifos / Q000032:analysis / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007306:Insecticides / Q000032:analysis / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D010634:Phenobarbital / Q000494:pharmacology*; D011728:Pyridones / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D018691:Excitatory Amino Acid Antagonists; D007306:Insecticides; D011728:Pyridones; C012587:3,5,6-trichloro-2-pyridinol; D003577:Cytochrome P-450 Enzyme System; D004390:Chlorpyrifos; D010634:Phenobarbital