Effects of dietary pyrazinamide, an antituberculosis agent, on the metabolism of tryptophan to niacin and of tryptophan to serotonin in rats

The effects of pyrazinamide on the metabolism of tryptophan to niacin and o f tryptophan to serotonin were investigated to elucidate the mechanism for pyrazinamide action against tuberculosis. Weanling rats were fed with a die t with or without 0.25% pyrazinamide for 61 days, Urine samples were period ically collected for measuring the tryptophan metabolites. The administrati on of pyrazinamide significantly increased the metabolites, 3-hydroxyanthra nilic acid and beyond, especially quinolinic acid, nicotinamide, N-1-methyl nicotinamide, and N-1-methyl-4-pyridone-3-carboxamide, and therefore signif icantly increased the conversion ratio of tryptophan to niacin and the bloo d NAD level, However, no difference in the upper metabolites of the tryptop han to niacin pathway such as anthranilic acid, kynurenic acid and xanthure nic acid was apparent between the two groups. No difference in the concentr ations of trytptophan and serotonin in the blood were apparent either. It i s suggested from these results that the action of pyrazinamide against tube rculosis is linked to the increase in turnover of NAD and to the increased content of NAD in the host cells.