A possible cellular mechanism of cisplatin-induced nephrotoxicity

Cisplatin, a relatively new antitumor agent, is associated with renal function impairment. The mechanism of cisplatin-induced nephrotoxicity is unknown. A mouse model was used to examine nephrotoxicity induced by cisplatin. This study demonstrates both morphologically and biochemically that mitochondrial damage may be associated with cisplatin-induced cellular toxicity. The morphological changes are evident after 72 h following a single 10 mg/kg i.p. dose of cisplatin. Biochemical changes also follow the morphological abbreviations. In vitro incubation of cisplatin with cells also shows a decline in Rhodamine 123 fluorescence with time, which is indicative of mitochondrial damage. The present findings suggest the possibility that the nephrotoxic effects of cisplatin may be related to a mitochondrial damage.