The effects of differential induction of cytochrome P-450, carboxylesterase and glutathione S-transferase activities on malathion toxicity in mice

The organophosphorous pesticide malathion is metabolized by three hepatic enzyme systems: the microsomal cytochrome P-450-dependent monooxygenase system, the microsomal carboxylesterases, and the cytosolic glutathione S-transferases. We produced differential induction of these three enzyme systems in mice with phenobarbital and 2(3)-tert-butyl-4-hydroxyanisole (BHA) and examined the effects of the induction on the inhibition of acetylcholinesterases by malathion. Phenobarbital not only significantly induced hepatic microsomal cytochrome P-450 (p < 0.05) but also increased microsomal carboxylesterase activity (p < 0.05). BHA not only increased the activity of microsomal carboxylesterases (p < 0.05) but also substantially increased cytosolic glutathione S-transferase activity (p < 0.05). Despite the differential effects of phenobarbital and BHA on the three enzyme systems, neither agent protected the mice against malathion toxicity