In vitro nephrotoxicity caused by 1,1,2-trichlorovynylcysteine

Nephrotoxicity of trichlorovinylcysteine (TCVC), a metabolite of tetrachloroethylene, was evaluated in vitro in male and female three months old Wistar rats by means of the renal cortical slice model. Concentrations between 0.4-4.0 moles/incubation (0.1-1.0 mM) caused, in both sexes, a dose-dependent increase of malondialdehyde (MDA), expression of lipid peroxidation, in the incubation medium and decrease of p-aminohippuric acid (PAH) uptake, expression of a reduced accumulation of the organic anions. A 1 mM concentration of aminooxyacetic acid (AOAA), a specific inhibitor of ß-lyase, significantly prevented lipid peroxidation (p<0.001) and PAH uptake decrease (p<0.01) induced by a 1.0 mM concentration of TCVC in both sexes. On the contrary, 200 M concentration probenecid (PROB), a selective inhibitor of organic anion transport, showed no protective effects against TCVC toxicity. The table summarizes the results expressed as per cent of the respective controls. In conclusion, TCVC causes nephrotoxic effects in vitro, probably by means of a thiol produced via ß-lyase; the lack of the protective effect of PROB may indicate that TCVC uses transport systems different from those of organic anion.