An ESR and spectrophotometric study of the denitration of nitroheterocyclic drugs by liver homogenates and their metabolic consumption by liver microsomes from cytochrome P-450-induced mice

This work extends a previous study on the mechanism of hepatic denitration of two nitroheterocyclic drugs (NHCD), quinifuryl and nitracrine, in which the release of nitric oxide (NO) from these compounds can be accompanied by the formation of a NO-heme iron complex. Pretreating mice with three inducers of cytochrome P-450 (phenobarbital, clophen A50 and butylated hydroxytoluene (BHT)) increased the yield of the nitrosyl complex which correlated with a rise in the cytochrome P-450 content of mouse liver microsomes. In contrast, treating the animals with β-naphthoflavone decreased the complex yield while still increasing P-450 content. Treating the animals with any of the above inducers significantly increased the rate of NHCD metabolism in mouse liver microsomes. Based on these results, a possible mechanism for hepatic NHCD denitration is discussed.