Vroomen L H, van Ommen B, van Bladeren P J
State Institute for Quality Control of Agricultural Products, Toxicology Section, Bornsesteeg 45, 6708 PD Wageningen, The Netherlands.
Toxicol In Vitro. 1987;1(2):97-104. doi: 10.1016/0887-2333(87)90007-5.
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-1alpha,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.
硝基呋喃类药物呋喃唑酮在有氧和无氧条件下均可被大鼠肝微粒体代谢，来自3-甲基胆蒽诱导的雄性大鼠的微粒体代谢速率分别为3.52和4.26 nmol/mg蛋白质/分钟。形成的两种主要代谢产物是众所周知的3-(4-氰基-2-氧代丁烯基氨基)-2-恶唑烷酮和2,3-二氢-3-氰基甲基-2-羟基-5-硝基-1α,2-二-(2-氧代-恶唑烷-3-基)亚氨基甲基呋喃并[2,3-b]呋喃（分别占总可提取放射性的16.6%和16.4%）。细胞色素P-450不参与呋喃唑酮的转化，呋喃唑酮被大鼠肝微粒体转化为与用纯化的NADPH-细胞色素P-450还原酶（一种微粒体还原酶）孵育时获得的产物相同的产物。在代谢过程中，相当数量的物质（占总代谢产物的2-3%）与微粒体蛋白共价结合。这种共价结合可通过添加谷胱甘肽来抑制，这也导致几乎完全从非极性代谢产物转变为水溶性代谢产物。未检测到呋喃唑酮与添加的小牛胸腺DNA之间的相互作用。
