Stimulatory effect of cisplatin on production of lipid peroxidation in renal tissues

Cisplatin (cis-diamminedichloroplatinum II), an anticancer chemotherapeutic agent with the dose-limiting side effect of nephrotoxicity, caused a statistically significant increase in lipid peroxidation, monitored by measuring the production of malondialdehyde, in rat kidney 72 hr after injection. Treatment of rats beforehand with the antioxidant alpha-tocopherol or N-N'-diphenyl-p-phenylenediamine (DPPD) effectively decreased such peroxidation. DPPD was a more effective inhibitor than alpha-tocopherol, since it is known for its ability to scavenge free radicals more powerfully. The ability of renal cortical slices to accumulate p-aminohippurate (PAH) was examined as a biochemical parameter that would change in nephrotoxicity. The ability to accumulate PAH by the incubated slices decreased 72 hr after administration of cisplatin. The pretreatment with DPPD prevented the decrease in PAH accumulation in the slices from rats treated with cisplatin. Structural changes of the renal proximal tubule caused by cisplatin, analyzed in a transmission electron microscope, were also prevented by the pretreatment with DPPD. The results suggest that cisplatin affects renal tissues in which free radicals generated by cisplatin may interact with membrane lipids to cause the production of lipid peroxidation, which affects both cellular structure and function.