MODIFICATION OF CISPLATIN-INDUCED RENAL P-AMINOHIPPURATE UPTAKE ALTERATION AND LIPID-PEROXIDATION BY THIOLS, GINKGO-BILOBA EXTRACT, DEFEROXAMINE AND TORBAFYLLINE

To determine whether inhibition of lipid peroxidation modifies cisplat in-induced changes of renal p-aminohippurate (PAH) uptake, we examined the effects of various radical scavengers and torbafylline on cisplat in-induced lipid peroxidation and PAH accumulation changes in rat rena l cortical slices. Renal cortical slices were incubated with different cisplatin concentrations (0.3, 0.6, 1.0 mg/ml) in the presence of eit her glutathione, N-acetylcysteine, the iron chelator deferoxamine, Gin kgo biloba extract or the xanthine derivate torbafylline. Lipid peroxi dation monitored as the production of malondialdehyde (MDA) was stimul ated by increasing cisplatin concentrations in a dose-related manner. At a cisplatin concentration of 1.0 mg/ml, MDA production was twofold compared to controls (0.69 +/- 0.06 vs. 1.36 +/- 0.07 nmol/mg; p < 0.0 5). In turn, cisplatin decreased PAH uptake of kidney slices dose-depe ndently from 13.3 +/- 1.3 to 2.6 +/- 0.2 (p < 0.01). All agents tested inhibited cisplatin-induced lipid peroxidation; however, at a cisplat in concentration of 1.0 mg/ml, none of them prevented the decline of c isplatin-induced PAH uptake. Of the agents tested, deferoxamine proved to be the most effective antioxidant, completely inhibiting cisplatin -induced lipid peroxidation but in contrast preventing the decrease in PAH uptake only at a cisplatin concentration of 0.3 mg/ml. No strict association between lipid peroxidation and decline of PAH uptake was f ound, suggesting that lipid peroxidation may only in part participate in cisplatin-induced alterations of PAH uptake.