MECHANISM OF S-(1,2-DICHLOROVINYL)GLUTATHIONE-INDUCED NEPHROTOXICITY

S-(1,2-Dichlorovinyl)glutathione and S-(1,2-dichlorovinyl)-DL-cysteine are potent nephrotoxins. Agents that inhibit .gamma.-glutamyl transpeptidase, cysteine conjugate .beta.-lyase, and renal organic anion transport systems, namely L-(.alpha.S,5S)-.alpha.-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (AT-125), aminooxyacetic acid, and probenecid, respectively, protected against S-conjugate-induced nephrotoxicity. Furthermore, S-(1,2-dichlorovinyl)-DL-.alpha.-methylcysteine, which cannot be cleaved by cysteine conjugate .beta.-lyase, was not nephrotoxic. These results strongly support a role for renal .gamma.-glutamyl transpeptidase, cysteine conjugate .beta.-lyase, and organic anion transport systems in S-(1,2-dichlorovinyl)glutathione- and S-(1,2,-dichlorovinyl)cysteine-induced nephrotoxicity.