PT  - JOURNAL ARTICLE
AU  - A A Elfarra
AU  - R B Baggs
AU  - M W Anders
TI  - Structure-nephrotoxicity relationships of S-(2-chloroethyl)-DL-cysteine and analogs: role for an episulfonium ion.
DP  - 1985 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 512--516
VI  - 233
IP  - 2
4099  - http://jpet.aspetjournals.org/content/233/2/512.short
4100  - http://jpet.aspetjournals.org/content/233/2/512.full
SO  - J Pharmacol Exp Ther1985 May 01; 233
AB  - 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.