Effect of cisplatin on in vitro production of lipid peroxides in rat kidney cortex.

Cisplatin (cis-diamminedichloroplatinum II), an antitumor agent with a dose-limiting adverse effect of nephrotoxicity, increased lipid peroxidation in a time- and concentration-dependent manner in rat renal slices incubated in vitro. The addition of an antioxidant, N-N'-diphenyl-p-phenylenediamine (DPPD), to the incubation medium completely inhibited this increase. We also studied the in vitro effects of agents that modify cisplatin nephrotoxicity on lipid peroxidation in the slices caused by cisplatin. Mannitol, which protects against cisplatin nephrotoxicity, almost completely inhibited the increase in lipid peroxidation caused by cisplatin. Methionine, which potentiates cisplatin nephrotoxicity, made the slices more susceptible to peroxidation. The decrease with cisplatin in p-aminohippurate (PAH) accumulation in incubated kidney cortical slices, the accumulation being a representative biochemical process in the transport ability of renal cells, was partially inhibited when DPPD was in the medium. The results suggested that cisplatin directly affected renal tissues in which free radicals generated by cisplatin may interact with membrane lipids to cause the production of lipid peroxides that damage membrane function. Compounds that modify cisplatin nephrotoxicity such as mannitol and methionine may act by affecting the production of renal lipid peroxides by cisplatin.