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  • Title: Amelioration of cisplatin toxicity in rat renal cortical slices by dithiothreitol in vitro.
    Author: Zhang JG, Zhong LF, Zhang M, Ma XL, Xia YX, Lindup WE.
    Journal: Hum Exp Toxicol; 1994 Feb; 13(2):89-93. PubMed ID: 7908816.
    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 malondialdehyde (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 l-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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