Effect of nicotinamide administration to rats on the liver microsomal drug metabolizing enzymes

A single injection or 3 successive injections of nicotinamide (500 mg/kg body wt) increased NADPH-cytochrome c reductase and aniline hydroxylase activities of rat liver microsomes without changing cytochrome P-450 content. Oral administration of nicotinamide for 2 weeks resulted in significant increase in cytochrome P-450, indicating that nicotinamide was an inducer of cytochrome P-450 though its potency was weak. A kinetic study indicated that microsomes isolated from control rats contained only high affinity (low Km) form of aniline hydroxylase while microsomes isolated from nicotinamide-treated rats contained more high affinity form and a newly appeared-low affinity (high Km) form. These results suggest that there exist at least 2 different cytochrome P-450s participating in aniline hydroxylation in rat liver microsomes and nicotinamide induces the high Km form. Ethanol or nicotinamide consumption for 2 weeks resulted in enhancement of high affinity form and appearance of low affinity form but with slightly different Km values.