Elfarra A A, Baggs R B, Anders M W
J Pharmacol Exp Ther. 1985 May;233(2):512-6.
1,2-Dichloroethane produces kidney damage, but the mechanism is unclear. Cysteine conjugates, which could arise from S-(2-chloroethyl)glutathione or S-(2-chloroethyl)cysteine have been identified. In this study, rats given S-(2-chloroethyl)-DL-cysteine (100 mg/kg i.p.) showed significant increases in blood urea nitrogen and urine glucose concentrations. Histopathological examination of kidneys, 36 hr after treatment showed acute proximal tubular nephrosis and punctuate glomerular necrosis. No hepatic lesions were seen and serum glutamate-pyruvate transaminase activities were only elevated slightly. The extent of S-(2-chloroethyl)-DL-cysteine renal toxicity was dose- and time-dependent. Equimolar doses of analogs of S-(2-chloroethyl)-DL-cysteine, S-ethyl-L-cysteine, S-(2-hydroxyethyl)-N-acetyl-DL-cysteine, S-(2-hydroxyethyl)-DL-cysteine, or S-(3-chloropropyl)-DL-cysteine, failed to produce nephrotoxicity; rats given L-cysteine (100 mg/kg i.p.), S-ethyl-L-cysteine (100 mg/kg i.p.) or probenecid (60 mg/kg i.p.) 30 min before receiving S-(2-chloroethyl)-DL-cysteine had significant reductions of the S-(2-chloroethyl)-DL-cysteine-induced blood urea nitrogen and urine glucose elevations. These results show that S-(2-chloroethyl)-DL-cysteine is a potent, selective nephrotoxin that may be responsible for the renal damage associated with 1,2-dichloroethane. The formation of an episulfonium ion plays an important role in S-(2-chloroethyl)-DL-cysteine-induced nephrotoxicity. The protection against renal damage provided by S-ethyl-L-cysteine or probenecid may involve competition with S-(2-chloroethyl)-DL-cysteine for cellular or transport binding sites.
1,2 - 二氯乙烷会导致肾脏损伤，但其机制尚不清楚。已鉴定出可能由S - (2 - 氯乙基)谷胱甘肽或S - (2 - 氯乙基)半胱氨酸产生的半胱氨酸共轭物。在本研究中，腹腔注射S - (2 - 氯乙基)-DL - 半胱氨酸（100毫克/千克）的大鼠血尿素氮和尿葡萄糖浓度显著升高。治疗36小时后对肾脏进行组织病理学检查显示急性近端肾小管肾病和点状肾小球坏死。未观察到肝脏病变，血清谷丙转氨酶活性仅略有升高。S - (2 - 氯乙基)-DL - 半胱氨酸的肾毒性程度呈剂量和时间依赖性。等摩尔剂量的S - (2 - 氯乙基)-DL - 半胱氨酸类似物，如S - 乙基 - L - 半胱氨酸、S - (2 - 羟乙基)-N - 乙酰 - DL - 半胱氨酸、S - (2 - 羟乙基)-DL - 半胱氨酸或S - (3 - 氯丙基)-DL - 半胱氨酸，均未产生肾毒性；在接受S - (2 - 氯乙基)-DL - 半胱氨酸前30分钟腹腔注射L - 半胱氨酸（100毫克/千克）、S - 乙基 - L - 半胱氨酸（100毫克/千克）或丙磺舒（60毫克/千克）的大鼠，S - (2 - 氯乙基)-DL - 半胱氨酸诱导的血尿素氮和尿葡萄糖升高显著降低。这些结果表明，S - (2 - 氯乙基)-DL - 半胱氨酸是一种强效的选择性肾毒素，可能是与1,2 - 二氯乙烷相关的肾脏损伤的原因。硫鎓离子的形成在S - (2 - 氯乙基)-DL - 半胱氨酸诱导的肾毒性中起重要作用。S - 乙基 - L - 半胱氨酸或丙磺舒对肾脏损伤的保护作用可能涉及与S - (2 - 氯乙基)-DL - 半胱氨酸竞争细胞或转运结合位点。
