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.
Singh
G
G
Ontario Cancer Foundation, Hamilton Regional Cancer Centre, Ontario, Canada.
D000818:Animals; D001806:Blood Urea Nitrogen; D002478:Cells, Cultured; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D003576:Electron Transport Complex IV / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D020112:Rhodamine 123; D012235:Rhodamines
D012235:Rhodamines; D020112:Rhodamine 123; D003404:Creatinine; D003576:Electron Transport Complex IV; D002945:Cisplatin