NEW PLATINUM COMPLEX-COMPOUNDS WITH REDUCED NEPHROTOXICITY DISCOVEREDIN LONG-TERM HISTOCULTURE OF HUMAN RENAL CORTICAL TISSUE

Cisplatinum is often effective in cancel treatment, but potent nephrot oxicity limits its clinical use. We have synthesized six new platinum compounds with the goal of reducing toxicity while maintaining efficac y. We initially tested drugs at 5 x 10(-4)M with 48 hours exposure in monolayer cultures of primary rabbit proximal tubular cells and human renal cortical cells with the MTT endpoint to measure toxicity. Drug c oncentration of 10(-3)M, 10(-4)M and 10(-5)M with 72 hours exposure we re used for human renal cortical tissues in 7 week sponge-gel-supporte d histoculture with toxicity measured by the glucose-consumption endpo int. From these studies, we determined that the new platinum drugs hav e lower nephrotoxicity than cisplatinum.