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Modification of Cisplatin-Induced Renal p-Aminohippurate Uptake Alteration and Lipid Peroxidation by Thiols, Ginkgo biloba Extract, Deferoxamine and Torbafylline
G. Inselmann a , A. Blöhmer b , W. Kottny b , U. Nellessen a , H. Hänel c , H.T. Heidemann b
18 December 2008
Nephrotoxicity, Cisplatin, Renal <italic>p</italic>-aminohippurate uptake, Lipid peroxidation, Glutathione, N-Acetylcysteine, Deferoxamine, <italic>Gingko biloba</italic> extract, Torbafylline
Abstract
To determine whether inhibition of lipid peroxidation modifies cisplatin-induced changes of renal p-aminohippurate (PAH) uptake, we examined the effects of various radical scavengers and torbafylline on cisplatin-induced lipid peroxidation and PAH accumulation changes in rat renal cortical slices. Renal cortical slices were incubated with different cisplatin concentrations (0.3, 0.6, 1.0 mg/ml) in the presence of either glutathione, N-acetylcysteine, the iron chelator deferoxamine, Ginkgo biloba extract or the xanthine derivate torbafylline. Lipid peroxidation monitored as the production of malondialdehyde (MDA) was stimulated 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 < 0.05). In turn, cisplatin decreased PAH uptake of kidney slices dose-dependently from 13.3 ± 1.3 to 2.6 ± 0.2 (p < 0.01). All agents tested inhibited cisplatin-induced lipid peroxidation; however, at a cisplatin concentration of 1.0 mg/ml, none of them prevented the decline of cisplatin-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 found, suggesting that lipid peroxidation may only in part participate in cisplatin-induced alterations of PAH uptake.
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