Comparative Analysis of Cell Injury after Exposure to Antitumor Platinum Derivatives in Kidney Tubular Epithelial Cells

Background: Platinum derivatives differ in effectiveness and safety. The purpose of this study is to compare differences in the mechanism of nephrotoxicity among these derivatives. Methods: LLC-PK1 cells were used as a model of tubular epithelial cells. Cytotoxicity was evaluated by WST-1 assay, and cellular accumulation of platinum was examined by inductively coupled plasma mass spectrometer. As indexes of necrosis and apoptosis, lactate dehydrogenase release, DNA fragmentation and caspase 3 activation were examined. Results: In terms of cytotoxicity, the derivatives ranked in the order of oxaliplatin > cisplatin > nedaplatin > carboplatin, being comparable with that for the level of platinum accumulated in LLC-PK1 cells. Lactate dehydrogenase release and DNA fragmentation were observed following treatment with all the derivatives, but were lowest for carboplatin. In terms of activating caspase 3, the order was cisplatin > nedaplatin > oxaliplatin > carboplatin. Conclusion: Cytotoxicity by the derivatives was dependent on cellular accumulation of platinum and suggested to be mediated by apoptosis and necrosis; however, contributions differed among the derivatives.