An assessment of cadmium toxicity on cytochrome P-450 and flavin monooxygenase-mediated metabolic pathways of dimethylaniline in male rabbits

Cadmium is an environmental pollutant and its effect on the in vitro metabolism of N,N-dimethylaniline (DMA) using male rabbits was investigated. Activities of cytochrome P-450 and FMO-dependent monooxygenases were studied using hepatic microsomes. Following CdCl₂ (i.p.) administration (6 mg/kg/day for 6 days), both DMA-N-oxidation and DMA-N-demethylation decreased by 86%. The effects of CdCl₂ on the phenobarbitone (PB)-induced form of P-450 were also studied. Intraperitoneal pretreatment of rabbits with PB (5 mg/kg/day for 5 days) increased N-demethylation by 82%, while N-oxidation decreased by 49%. Both reactions decreased significantly on additional treatment with CdCl₂. Premethazine (5 mg/kg/day for 5 days) did not produce any change in the activities of either enzyme. The enzymes remained unaffected by CdCl₂ treatment in promethazine-pretreated animals thus confirming its role as a hepatoprotective agent.