Alterations of the renal function in the isolated perfused rat kidney system after in vivo and in vitro application of S-(1,2-dichlorovinyl)-L-cysteine and S-(2,2-dichlorovinyl)-L-cysteine

Abstract

The nephrotoxic effects of the two isomers S-(1,2-dichlorovinyl)-L-cysteine (1,2-DCVC) and S-(2,2-dichlorovinyl)-L-cysteine (2,2-DCVC) were investigated comparatively in the isolated perfused rat kidney with two different treatment regimens. In the first approach, the kidneys were exposed to the test compounds dissolved in the perfusion media after removal from the animal. In the second approach the test compounds were 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 1,2-DCVC produced concentration- and time-dependent nephrotoxicity with both treatment regimens, as indicated by the impairment of glucose reabsorption, the increase of protein excretion and of gamma-glutamyltransferase and alkaline phosphatase activities in urine. In contrast to the marked toxicity observed after in vivo and in vitro administration of 1,2-DCVC, the geminal isomer, 2,2-DCVC, was not nephrotoxic at all concentrations (0.5 and 2.5 mM in vitro, 40 and 70 mg/kg in vivo) investigated.