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 denitra tion 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 m ice with three inducers of cytochrome P-450 (phenobarbital, clophen A5 0 and butylated hydroxytoluene (BHT)) increased the yield of the nitro syl complex which correlated with a rise in the cytochrome P-450 conte nt of mouse liver microsomes. In contrast, treating the animals with b eta-naphthoflavone decreased the complex yield while still increasing P-450 content, Treating the animals with any of the above inducers sig nificantly increased the rate of NHCD metabolism in mouse liver micros omes. Based on these results, a possible mechanism for hepatic NHCD de nitration is discussed.