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Selenium-induced Protection against cis-Diamminedichloroplatinum(II) Nephrotoxicity in Mice and Rats¹

Department of Radiochemistry, Interfaculty Reactor Institute, Mekelweg 15, 2629 JB Delft [G. S. B., C. J. A. v. d. H., J. J. M. d. G.]; Department of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam [G. L., J. G. M.]; and Department of Pharmacochemistry, Molecular Toxicology, Free University, De Boelelaan 1083, 1081 HV Amsterdam [G. S. B., N. P. E. V.], The Netherlands

The influence of selenium on cis-diamminedichloroplatinum(II) (c-DDP) nephrotoxicity in mice and rats was assessed, using single doses of both compounds. Sodium selenite, 2 mg of selenium per kg, given 1 h before c-DDP, greatly reduced blood urea nitrogen and creatinine levels and morphological kidney damage in both BALB/c mice and Wistar rats, while administration 1 h after c-DDP did not. Liver toxicity of selenium was evaluated by measuring serum glutamic pyruvate transaminase and serum glutamic oxalate transaminase and by routine histology. No liver damage was observed in animals treated with sodium selenite, 2 mg of selenium per kg, and physiological saline or c-DDP. Pretreatment with sodium selenite did not reduce the antitumor activity of c-DDP against MPC 11 plasmacytoma or Prima breast tumor in BALB/c mice.

The present results indicate that sodium selenite may provide protection against c-DDP nephrotoxicity, when it is given before c-DDP. Moreover, selenium has an antineoplastic activity against several tumors. The combination of these qualities may open new perspectives in cancer chemotherapy.

¹ This work was supported by the Koningin Wilhelmina Fonds, Project IKW 86-18.

² To whom requests for reprints should be addressed.

Received 9/20/88. Revised 12/30/88. Accepted 2/ 9/89.

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