Abstract
S-(1,2-rmDichlorovinyl)glutathione and S-(1,2- dichlorovinyl)- dl-cysteine are potent nephrotoxins. Agents that inhibit γ-glutamyl transpeptidase, cysteine conjugate β-lyase, and renal organic anion transport systems, namely l -(αS,5S)-α'- amino-3- chloro-4,5- dinydro-5- isoxazoleacetic acid (AT-125), aminooxyacetic acid, and probenecid, respectively, protected against S-conjugate-induced nephrotoxicity. Furthermore, S-(1,2- dichlorovinyl)- dl -α- methylcysteine , which cannot be cleaved by cysteine conjugate β-lyase, was not nephrotoxic. These results strongly support a role for renal γ-glutamyl transpeptidase, cysteine conjugate β-lyase, and organic anion transport systems in S-(1,2-dichlorovinyl)glutathione- and S-(1,2,-dichlorovinyl)cysteine-induced nephrotoxicity.
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