Vroomen L H, Groten J P, van Muiswinkel K, van Velduizen A, van Bladeren P J
State Institute for Quality Control of Agricultural Products, Department of Toxicology, Wageningen, The Netherlands.
Chem Biol Interact. 1987;64(1-2):167-79. doi: 10.1016/0009-2797(87)90069-x.
Furazolidone (N-(5-nitro-2-furfurylidene)-3-amino-2-oxazolidone) is metabolized by swine liver microsomes under aerobic and anaerobic conditions (rate: 2.55 and 3.25 nmol/mg protein/min, respectively). Covalent binding to microsomal protein amounted aerobically to 0.29 nmol/mg protein/min. Of all amino acids tested, only addition of cysteine to the incubation mixture decreased microsomal protein binding of furazolidone, indicating that covalent binding may occur at protein thiol groups. Two known metabolites of furazolidone, 3-(4-cyano-2-oxobutylidene-amino)-2-oxazolidone and 2,3 dihydro-3-cyano-methyl-2-hydroxyl-5-nitro-1 alpha,2-di(2-oxo-oxazolidin-3-yl) iminomethyl-furo[2,3-b] furan, were minor metabolites. At least 50% of total metabolites is formed by swine liver microsomes via a reductive process of furazolidone as indicated by the formation of a furazolidone-mercaptoethanol conjugate after the addition of mercaptoethanol to the incubation mixture. The conjugate was identified as 3-(4-cyano-3-beta-hydroxyethylmercapto-2-oxobutylidene amino)-2-oxazolidone, indicating that the open-chain acrylonitrile-derivative is the reactive intermediate of furazolidone which also may be responsible for interaction with protein.
呋喃唑酮（N-(5-硝基-2-糠叉基)-3-氨基-2-恶唑烷酮）在需氧和厌氧条件下均可被猪肝微粒体代谢（速率分别为2.55和3.25 nmol/mg蛋白质/分钟）。与微粒体蛋白的共价结合在需氧条件下为0.29 nmol/mg蛋白质/分钟。在所有测试的氨基酸中，只有向孵育混合物中添加半胱氨酸会降低呋喃唑酮与微粒体蛋白的结合，这表明共价结合可能发生在蛋白的巯基上。呋喃唑酮的两种已知代谢产物，3-(4-氰基-2-氧代丁叉基氨基)-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[2,3-b]呋喃，是次要代谢产物。如向孵育混合物中添加巯基乙醇后形成呋喃唑酮-巯基乙醇缀合物所示，至少50%的总代谢产物是由猪肝微粒体通过呋喃唑酮的还原过程形成的。该缀合物被鉴定为3-(4-氰基-3-β-羟乙基巯基-2-氧代丁叉基氨基)-2-恶唑烷酮，表明开链丙烯腈衍生物是呋喃唑酮的反应中间体，它也可能负责与蛋白质的相互作用。
