Boyd M R
Adv Exp Med Biol. 1981;136 Pt B:865-79.
Furan derivatives occur widely in the environment, and several of these compounds cause necrosis of target cells within certain organs, including the liver, the kidneys, and the lungs. The tissue specificity may vary from compound to compound. For individual compounds, the specificity may be greatly influenced by the species, sex, and age of the test animal and by the prior exposure of the animal to inducers of drug metabolism. Studies in vitro and in vivo indicate that cytochrome P-450 enzymes in the target tissues mediate the formation of highly reactive, electrophilic furan metabolites that bind covalently to tissue macromolecules. Epoxides are suspected, but not proven, to be the proximate or ultimate toxic metabolites of furans. One study suggested that epoxide hydratase might influence the covalent binding of a furan derivative in vitro, but similar investigations with other furans have been negative. Glutathione (GSH) can inhibit the covalent binding of reactive furan metabolites in vitro, presumably by forming less reactive, water-soluble conjugates with the activated furans. GSH-furan conjugate formation can occur nonenzymatically, and a study with 4-ipomeanol indicated that cytosolic enzyme preparations did not enhance the amounts of conjugates produced. It is likely that GSH provides a major mechanism for detoxification of some furans in vivo.
呋喃衍生物广泛存在于环境中，其中几种化合物会导致某些器官（包括肝脏、肾脏和肺）内的靶细胞坏死。不同化合物的组织特异性可能有所不同。对于单个化合物而言，其特异性可能会受到实验动物的物种、性别和年龄以及动物先前接触药物代谢诱导剂的极大影响。体外和体内研究表明，靶组织中的细胞色素P - 450酶介导了高反应性亲电呋喃代谢物的形成，这些代谢物会与组织大分子共价结合。环氧化物被怀疑是呋喃的直接或最终有毒代谢物，但尚未得到证实。一项研究表明，环氧水解酶可能会在体外影响呋喃衍生物的共价结合，但对其他呋喃进行的类似研究结果均为阴性。谷胱甘肽（GSH）在体外可抑制反应性呋喃代谢物的共价结合，大概是通过与活化的呋喃形成反应性较低的水溶性缀合物来实现的。GSH - 呋喃缀合物的形成可以非酶促方式发生，一项针对4 - 异戊烯醇的研究表明，胞质酶制剂并不会增加缀合物的生成量。GSH很可能为体内某些呋喃的解毒提供了主要机制。
