Effect of the antioxidant N,N1-diphenyl-p-phenylenediamine (DPPD) on bromobenzene metabolism and toxicity in isolated hepatocytes.

Bromobenzene induced cytotoxicity in isolated hepatocytes was partly prevented by the antioxidant DPPD (N,N'-diphenyl-p-phenylenediamine). This protection did not appear to be a result of an inhibition of lipid peroxidation but rather to an inhibition of the metabolic activation of bromobenzene. The extent of DPPD dependent inhibition of cytochrome P-450 catalyzed reactions appears to depend on the substrate being metabolized. Thus, whereas cytochrome P-450 catalyzed metabolism of bromobenzene and harmine was inhibited by DPPD, the N-dealkylation of aminopyrine was not. The results presented in this paper indicate the importance of evaluating the effect of antioxidants such as DPPD as inhibitors of bioactivation prior to drawing definitive conclusions regarding involvement of lipid peroxidation in drug induced cytotoxicity.