Quantitative studies of the metabolism of furazolidone by rat liver microsomes

Abstract The nitrofuran, furazolidone, is metabolized by rat liver microsomes under both aerobic and anaerobic conditions, the rates for microsomes from 3-methylcholanthrene-induced male rats being 3.52 and 4.26 nmol/mg protein/min, respectively. The two major metabolites formed are the well-known 3-(4-cyano-2-oxobutylideneamino)-2-oxazolidone, and 2,3-dihydro-3-cyanomethyl-2-hydroxy-5-nitro-1α,2-di-(2-oxo-oxazolidin-3-yl)iminomethylfuro[2,3- b ]furan (accounting for 16.6 and 16.4% of total extractable radioactivity, respectively). Cytochrome P -450 is not involved in the conversion of furazolidone, which was converted by rat liver microsomes to products identical to those obtained upon incubation with purified NADPH-cytochrome P -450 reductase, which is a microsomal reductase. During metabolism, a considerable amount of material (2–3% of total metabolites) became covalently bound to microsomal protein. This covalent binding could be inhibited by addition of glutathione, which also resulted in an almost complete shift from non-polar to water-soluble metabolites. No interaction of furazolidone with added calf thymus DNA was detected.