Inhibitory effect of nicotinamide to paraquat toxicity and the reaction site on complex I

The inhibitory effect and mechanism of action of nicotinamide to paraquat toxicity were studied in male Sprague-Dawley rats. Proteins of submitochondrial particles (SMP), especially of mol. wt. 25–30 kDa, in rat lungs were destroyed by paraquat radicals, and aggregated protein bands ∼100 kDa were observed by polyacrylamide electrophoresis. The competitive inhibition effects were observed of nicotinamide on NADH oxidation by paraquat via SMP in rat lungs and the K _i was 9.3 mM. The inhibitory effects of nicotinamide on lipid peroxidation by paraquat with rat lung and liver SMP were verified. The times of occurrence of dyspnea and death in rats after paraquat exposure were delayed by nicotinamide administration. The activity of NADH: ubiquinone reaction of NADH:ubiquinone oxidoreductase (complex I) in rat lung was reduced 24 h after paraquat exposure, and was protected by nicotinamide. The activity of NADH:ferricyanide reaction of complex I was, however, reduced by administration not only of paraquat but also nicotinamide. These results imply that nicotinamide is inhibitory to paraquat toxicity. Nicotinamide, paraquat, and ferricyanide may react at overlapping sites on complex I. Received: 14 April 1997 / Accepted: 13 May 1997