Amelioration of Cisplatin Toxicity in Rat Renal Cortical Slices by Dithiothreitol In vitro

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Abstract

1 The protective effects of dithiothreitol (DTT) on cisplatin-induced nephrotoxicity were investigated with rat renal cortical slices.

2 The nephrotoxic effects of cisplatin (2 mmol l-1) were manifested in several ways: the Na+ and water content were increased while K+ was decreased. The malondiadehyde (MDA) concentration in the slices and the lactate dehydrogenase (LDH) released into the medium were increased. The uptake of p-aminohippurate (PAH), the synthesis of glucose and the glutathione (GSH) concentration in the slices were all decreased.

3 Despite a DTT-related increase in platinum (Pt) uptake by the slices, DTT (0.5-2 mmol I-1 ) ameliorated all these toxic effects of cisplatin in a concentration related manner.

4 The results suggest that the protective mechanism of DTT is its antioxidative action, DTT is also a metal chelator, however, and so a protective effect via chelation of Pt by DTT cannot be excluded.

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