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Human & Experimental Toxicology
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Amelioration of Cisplatin Toxicity in Rat Renal Cortical Slices by Dithiothreitol In vitro

J.G. Zhang

Department of Toxicology, Dalian Medical College, Dalian 116023, People's Republic of China

L.F. Zhong

Department of Toxicology, Dalian Medical College, Dalian 116023, People's Republic of China

M. Zhang

Department of Toxicology, Dalian Medical College, Dalian 116023, People's Republic of China

X.L. Ma

Department of Toxicology, Dalian Medical College, Dalian 116023, People's Republic of China

Y.X. Xia

Department of Toxicology, Dalian Medical College, Dalian 116023, People's Republic of China

W.E. Lindup

Department of Pharmacology and Therapeutics, University of Liverpool, P.O. Box 147, Liverpool L69 3BX, UK

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.

Human & Experimental Toxicology, Vol. 13, No. 2, 89-93 (1994)
DOI: 10.1177/096032719401300205
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