Induction of xanthine oxidase and heme oxygenase and depression of liver drug metabolism by interferon: a study with different recombinant interferons.
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 antioxidant N-acetylcysteine 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.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005609:Free Radicals; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D007370:Interferon Type I / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D004364:Pharmaceutical Preparations / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014969:Xanthine Oxidase / Q000096:biosynthesis*
D005609:Free Radicals; D007370:Interferon Type I; D004364:Pharmaceutical Preparations; D013481:Superoxides; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D006419:Heme Oxygenase (Decyclizing); D014969:Xanthine Oxidase