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大鼠体内1,2,4-三氯苯的代谢:硫醇形成的检测

Metabolism of 1,2,4-trichlorobenzene in rats: examination of thiol formation.

作者信息

Bakke J E, Huwe J K, Mulford D J, Bergman A

机构信息

Biosciences Research Laboratory, US Department of Agriculture, Fargo, ND 58105.

出版信息

Xenobiotica. 1992 Feb;22(2):199-210. doi: 10.3109/00498259209046618.

DOI:10.3109/00498259209046618
PMID:1632109
Abstract
  1. More than 60% of oral doses of 14C-1,2,4-trichlorobenzene (ca. 21 mg/kg) administered to rats were excreted in bile as S-trichlorophenyl-mercapturic acid pathway metabolites. 2. The biliary metabolites were ultimately excreted in urine mainly as the isomeric mercapturic acids. 3. An acetylated glutathione conjugate was isolated as a major metabolite in bile (8% dose). The acetyl group was shown by mass spectrometry to be on the glutamyl moiety. 4. A glutamylcysteine conjugate of trichlorobenzene was also isolated from bile as a major metabolite (8% dose). 5. Trichlorothiophenols were deduced not to be intermediates or end-products of enzymic metabolism of trichlorobenzene in rats because 14C-2,4,5-trichlorothiophenol dosed i.p. to rats was excreted as the S-glucuronide (17% dose) and as S-(methylsulphonyl-dichlorophenyl)-mercapturic acid (36% dose).
摘要
  1. 给大鼠口服14C-1,2,4-三氯苯(约21毫克/千克),超过60%的口服剂量以S-三氯苯基-巯基尿酸途径代谢产物的形式经胆汁排泄。2. 胆汁中的代谢产物最终主要以异构巯基尿酸的形式经尿液排泄。3. 一种乙酰化谷胱甘肽缀合物作为胆汁中的主要代谢产物被分离出来(剂量的8%)。通过质谱分析表明乙酰基在谷氨酰部分。4. 三氯苯的谷氨酰半胱氨酸缀合物也作为主要代谢产物从胆汁中分离出来(剂量的8%)。5. 三氯苯硫酚被推断不是大鼠体内三氯苯酶促代谢的中间体或终产物,因为经腹腔注射给大鼠的14C-2,4,5-三氯苯硫酚以S-葡萄糖醛酸苷(剂量的17%)和S-(甲基磺酰基-二氯苯基)-巯基尿酸(剂量的36%)的形式排泄。

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