Effect of phenobarbital and 3-methylcholanthrene treatment on NADPH- and NADH-dependent production of reactive oxygen intermediates by rat liver nuclei

The effect of inducing the rat liver nuclear mixed-functions oxidase system phenobarbital or 3-methylcholanthrene on NADPH- and NADH-dependent production of reactive oxygen intermediates was evaluated. The inducing agents produced a 2-fold increase in cytochrome P-450, a 50 to 70% increase in NADPH-cytochrome c reductase activity, and a 20 to 30% increase in NADH-cytochrome c reductase activity. Associated with these increases was a corresponding increase in NADPH- and NADH-dependent production of hydroxyl radical (·OH)-like species and of H₂O₂. Rates of ·OH production were inhibited by catalase and partially sensitive to superioxide dismutase. The increase in nuclear production of ·OH-like species after drug treatment appears to be due a corresponding increase in H₂O₂ generation. In contrast to H₂O₂ and ·OH generation, production of thiobarbituric acid-reactive material by nuclei was not increased by the phenobartial or 3-methylcholanthrene treatment. Redox cycling such as menadione and paraquat increased oxygen radical generation to similar extents in the control and the induced nuclei. These results indicate that induction of the nuclear mixed-function oxidase system by phenobarbital or 3-methylcholanthrene can result isn a subsequent increase in productionn of reactive oxygen intermediates in the presence of either NADPH or NADH.