Elsevier

Biochemical Pharmacology

Volume 35, Issue 2, 15 January 1986, Pages 283-288
Biochemical Pharmacology

Mechanism of S-(1,2-dichlorovinyl)glutathione-induced nephrotoxicity

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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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