The reductive metabolism of the nitroaromatic flukicidal agent nitroxinil by liver microsomal cytochrome P-450.
Hepatic biotransformation of the flukicidal agent nitroxynil (3-iodo-4-hydroxy-5-nitrobenzonitrile) (I) has been studied with rat liver subcellular fractions as the source of enzymes: two metabolites, 3-iodo-4--hydroxy-5-aminobenzonitrile (II) and 3-iodo-4-hydroxy-5-nitrobenzamide (III) have been identified by standard analytical techniques (TLC, GLC and MS). The nitroaromatic reduction product (II) is formed in the hepatocyte in a process in which cytosol and endoplasmic reticulum enzymes cooperate. This formation is maximal in anaerobic conditions, but takes also place aerobically and in the absence of electrogenic cofactors. Cytochrome P-450 plays a major role in the denitrification process, and consequently could be the cellular site most exposed to damage by the intermediate arylhydroxylamine formed by reduction.
D000818:Animals; D000871:Anthelmintics / Q000378:metabolism*; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000201:enzymology*; D009596:Nitrophenols / Q000378:metabolism*; D009611:Nitroxinil / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism
D000871:Anthelmintics; D009596:Nitrophenols; D003577:Cytochrome P-450 Enzyme System; D009611:Nitroxinil