Interaction of parathion and malathion with hepatic cytochrome P-450 from rats treated with phenobarbital and carbon disulfide.

Alterations in the activity of drug-metabolizing enzymes and the concentration of cytochrome p-450 from liver microsomes of rats pretreated with phenobarbital for enzyme induction and later given a single oral dose (0.4 ml/kg) of carbon disulfide (CS2) have been examined. In vitro incubations of these microsomes with parathion and malathion showed no significant change in the amount of cytochrome p-450 from that present in the corresponding controls. This inhibition of oxidative desulfuration of these insecticides by microsomes from CS2-treated animals could be attributed to the prior binding with cytochrome p-450 of sulfur released from CS2 as confirmed from the results of spectral binding of SKF 525-A, parathion and malathion. These results lead to the conclusion that CS2, parathion and malathion undergo oxidative desulfuration in an analogous manner and that the metabolism of the insecticides is impaired in liver previously exposed to CS2.