ALTERATIONS OF THE RENAL-FUNCTION IN THE ISOLATED-PERFUSED RAT-KIDNEYSYSTEM AFTER IN-VIVO AND IN-VITRO APPLICATION OF S-(1,2-DICHLOROVINYL)-L-CYSTEINE AND S-(2,2-DICHLOROVINYL)-L-CYSTEINE

The nephrotoxic effects of the two isomers S-(1,2-dichlorovinyl)-L-cys teine (1,2-DCVC) and S-(2,2-dichlorovinyl)-L-cysteine (2,2-DCVC) were investigated comparatively in the isolated perfused rat kidney with tw o different treatment regimens. In the first approach, the kidneys wer e exposed to the test compounds dissolved in the perfusion media after removal from the animal. In the second approach the test compounds we re administered to rats in vivo and the nephrotoxicity was assessed in the isolated perfused kidney 6 h and 18 h post-treatment. The vicinal isomer 1,2DCVC produced concentration- and time-dependent nephrotoxic ity with both treatment regimens, as indicated by the impairment of gl ucose reabsorption, the increase of protein excretion and of gamma-glu tamyl-transferase and alkaline phosphatase activities in urine. In con trast to the marked toxicity observed after in vivo and in vitro admin istration of 1,2-DCVC, the geminal isomer, 2,2-DCVC, was not nephrotox ic at all concentrations (0.5 and 2.5 mM in vitro, 40 and 70 mg/kg in vivo) investigated.