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.