The nephrotoxicity of p-aminophenol. II. The effect of metabolic inhibitors and inducers.

Abstract Inducers and inhibitors of the microsomal mixed function oxidase system have no consistent effect upon the nephrotoxicity of p -aminophenol, or on binding of the compound in vivo to cell protein. p -[ ring - 3 H]Aminophenol was bound in vitro to kidney microsomal protein and to a lesser extent to liver. The binding was enhanced by preincubation of the p -aminophenol in air and inhibited by ascorbate, GSH, N 2 and NADPH. These findings indicate that in contrast to paracetamol hepatoxicity which is dependent upon the mixed function oxidase system, that nephrotoxicity of p -aminophenol is dependent upon oxidation to a toxic metabolite by some other pathway. A similar metabolite may be responsible for the nephrotoxic action of phenacetin.