Studies on nifurtimox nitroreductase activity in liver and other rat tissues.
Rat liver microsomes exhibit nifurtimox (NFX) nitroreductase activity, which is mostly NADPH-dependent and is completely abolished by heating and under an atmosphere of air. Pure carbon monoxide inhibits for 28% microsomal NFX nitroreductase activity while FAD 1 mM significantly enhances it. Smaller activities than in liver were found in brain, small intestine, testes, lung and heart. Rat liver cytosol also showed NFX nitroreductase activity using either hypoxanthine or N-methylnicotinamide as substrates. These activities were inhibited by allopurinol or menadione respectively. Results suggest that cytochrome P-450, NADPH cytochrome c reductase, xanthinoxidase and aldehyde oxidase are able to reduce NFX nitrogroups in rat liver and other tissues.
D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D006358:Hot Temperature; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009249:NADP / Q000494:pharmacology; D009547:Nifurtimox / Q000378:metabolism*; D009581:Nitrofurans / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D009581:Nitrofurans; D009249:NADP; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System; D009547:Nifurtimox; D010100:Oxygen