IN-VITRO COMPARATIVE-STUDY ON NEPHROTOXICITY OF CYCLOSPORINE-A, ITS METABOLITES M1, M17, M21, AND ITS ANALOGS CYCLOSPORINE-C AND CYCLOSPORINE-D IN SUSPENSIONS OF RABBIT RENAL CORTICAL-CELLS

The potential nephrotoxicity of cyclosporine A (CsA), its three main m etabolites : M1, M17 and M21, and its two analogues : cyclosporines C and D (CsC, CsD) was evaluated in vitro in suspensions of freshly isol ated rabbit renal proximal tubular cells. This assessment involved the measure of enzyme release in the incubation media and the determinati on of Na+/K+-ATPase activity and glutathione content directly in the t ubular cells. In vitro nephrotoxicity results of the six compounds tes ted could be respectively schematized as : CsA > CsD > CsC >M21>M17, M 1 It would be interesting to promote the study of promising CsC becaus e of its low nephrotoxicity and its high immunosuppressive potency as previously reported.