Chen K C, Dorough H W
Drug Chem Toxicol. 1980;3(3):305-18. doi: 10.3109/01480548009002225.
The formation of glutathione (GSH) conjugate in the detoxification of [Ring-UL-14C]-2,4-dinitrobromobenzene (DNBB) was investigated using rat liver cytosolic fraction. The mercapturic acid conjugate in rats was also studied by collection of urine of rats dosed with radioactive DNBB by intraperitoneal injection. The glutathione replaced the labile bromo atom and formed the conjugate, S-(2,4-dinitrophenyl)glutathione. The GSH conjugate was confirmed by amino acid analysis and by mass spectroscopy as well as co-cochromatography with the synthetic compound. The amount of formation of GSH conjugate was dependent on the amount of GSH added in the incubation mixture. When [Ring-UL-14C]-DNBB was dosed to rats, 69% and 17% of the radiocarbon was excreted via the urine and feces within 72 hours, respectively. The major radioactive metabolite present in the acid urine of DNBB treated was S-(2,4-dinitrophenyl)mercapturic acid accounting for 60% of the administered dose of radiocarbon. The mercapturic acid conjugate was identified similarly to methods used for identification of GSH conjugate. The data demonstrated that GSH conjugate, formed initially and then subsequently converted into the mercapturic acid excreted in the urine, was the major metabolic pathway in the metabolism of 2,4-dinitrobromobenzene.
利用大鼠肝脏胞质部分研究了[环 - UL - 14C]-2,4 - 二硝基溴苯（DNBB）解毒过程中谷胱甘肽（GSH）共轭物的形成。通过收集腹腔注射放射性DNBB的大鼠尿液，对大鼠体内的硫醚氨酸共轭物也进行了研究。谷胱甘肽取代了不稳定的溴原子，形成共轭物S - (2,4 - 二硝基苯基)谷胱甘肽。通过氨基酸分析、质谱以及与合成化合物的共色谱法证实了GSH共轭物。GSH共轭物的形成量取决于孵育混合物中添加的GSH量。当给大鼠注射[环 - UL - 14C]-DNBB时，72小时内分别有69%和17%的放射性碳通过尿液和粪便排出。DNBB处理的大鼠酸性尿液中存在的主要放射性代谢物是S - (2,4 - 二硝基苯基)硫醚氨酸，占给予放射性碳剂量的60%。硫醚氨酸共轭物的鉴定方法与用于鉴定GSH共轭物的方法类似。数据表明，GSH共轭物是2,4 - 二硝基溴苯代谢的主要代谢途径，它先形成，随后转化为经尿液排出的硫醚氨酸。
