Role of cytochrome P-450 in quinalphos toxicity: effect on hepatic and brain antioxidant enzymes in rats.
Quinalphos (QP), an organophosphate pesticide, is used in controlling the pests of a variety of crops. To understand the mechanism of the metabolic basis of the toxicity of QP it was thought pertinent to study the role of cytochrome P-450 (P450) and antioxidant enzyme systems. Albino rats treated orally with QP (0.52 and 1.04 mg/kg body weight) for 60 days showed a significant decrease in body, brain and liver weights. Hepatic P450 content and its dependent monooxygenases, namely aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin-O-deethylase (ERD), were induced to 1.8-2.5-fold, while neuronal AHH was induced to 1.8-fold following QP treatment (1.04 mg/kg) to animals. The hepatic antioxidant defence system, comprising catalase, glutathione (GSH) reductase, superoxide dismutase (SOD) and GSH peroxidase, was also significantly increased in QP-treated animals, while in the brain only catalase was increased and GSH reductase decreased. There was no significant change in hepatic GSH content and lipid peroxide levels in QP treated animals at any dose group in comparison with the control group. Pretreatment of rats with phenobarbitone (PB) or 3-methylcholanthrene (MC) (P450 inducers) prevented mortality caused by the LD50 dose of QP, whereas pretreatment with cobalt chloride (a P450 inhibitor) enhanced the mortality rate to 100% within 3 days. From the above study it can be inferred that the toxicity of QP may be due to the parent compound or its metabolite(s) produced prior to P450 oxidation and that the induction of P450 system by QP may be a defence mechanism.
Dwivedi
P D
PD
Food Toxicology Division, Industrial Toxicology Research Centre, Lucknow, India.
Das
M
M
Khanna
S K
SK
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D002374:Catalase / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015786:Cytochromes b5 / Q000378:metabolism; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007306:Insecticides / Q000633:toxicity*; D007928:Lethal Dose 50; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D015996:Survival Rate
D000975:Antioxidants; D007306:Insecticides; D009946:Organothiophosphorus Compounds; C009145:quinalphos; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D000110:Acetylcholinesterase