Induction of Xanthine Oxidase and Heme Oxygenase and Depression of Liver Drug Metabolism by Interferon: A Study with Different Recombinant Interferons

ABSTRACT Induction of xanthine oxidase in mouse liver by interferon (IFN) was studied with three different recombinant human leukocyte IFN molecules: IFLrA, IFLrD and the hybrid IFLrA/D(Bgl II). The ability of different IFN species to induce xanthine oxidase correlated with their ability to depress liver cytochrome P-450-dependent drug metabolism, supporting the hypothesis that reactive oxygen metabolites generated by xanthine oxidase might be responsible for this impairment of liver function by IFN. The antioxidan Nacetylcysteine protected in vivo against the depression of liver drug metabolism by IFLrA/D. IFLrA/D was also found to induce liver microsomal heme oxygenase, an effect that was probably secondary to the observed depression of cytochrome P-450.