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 me tabolic basis of the toxicity of QP it was thought pertinent to study the role of cytochrome P-450 (P450) and antioxidant enzyme systems. al bino 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 weight s. 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-fo ld following QP treatment (1.04 mg/kg) to animals. The hepatic antioxi dant 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 chang e in hepatic GSH content and lipid peroxide levels in QP treated anima ls at any dose group in comparison with the control group. Pretreatmen t 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 mort ality rate to 100% within 3 days. From the above study it can be infer red that the toxicity of QP may be due to the parent compound or its m etabolite(s) produced prior to P450 oxidation and that the induction o f P450 system by QP may be a defence mechanism. (C) 1998 Elsevier Scie nce Ltd. All rights reserved.