Metabolism of 14C-labelled 5-nitro-1,2,4-triazol-3-one by rat liver microsomes--evidence for the participation of cytochrome P-450.
In the present study, we synthesized 14C-labelled 5-nitro-1,2,4-triazol-3-one (NTO) and investigated its hepatic metabolism by dexamethasone-induced murine hepatic microsomes. Under the nitrogen atmosphere, 5-amino-1,2,4-triazol-3-one was the only detected metabolite of NTO. The microsomal nitroreductase activity was dependent on NADPH, totally inhibited by carbon monoxide and partially inhibited by oxygen. In aerobic conditions, beside a low amount of amine, the major metabolite formed is the 5-hydroxy-triazolone, urazole. This compound resulted from the oxidative denitrification of NTO, which produced equivalent amount of nitrite. This reaction, like the nitroreductase activity, was dependent on NADPH and totally inhibited by carbon monoxide. Both nitroreduction and oxidative denitrification were inhibited by imidazole-related inhibitors: miconazole and methimazole, and to a less extent by N-octylamine. The microsomal denitrification was induced by the treatment of rats with dexamethasone and phenobarbital. The microsomal reductase activity is present in untreated rat microsomes, and recovered with various inducers. The results of this study indicate the role played by cytochrome P-450 in the metabolism of NTO, supported by its transformation with reconstituted cytochrome P-450 systems.[1]References
- Metabolism of 14C-labelled 5-nitro-1,2,4-triazol-3-one by rat liver microsomes--evidence for the participation of cytochrome P-450. Le Campion, L., Delaforge, M., Noel, J.P., Ouazzani, J. Eur. J. Biochem. (1997) [Pubmed]
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