[Studies on protective effect of selenium on the nephrotoxicity of cis-diamminedichloroplatinum (CDDP) in mice].
Protective effect of sodium selenite (Se) on the nephrotoxicity of cis-diamminedichloroplatinum (CDDP) was studied in mice. The administration of CDDP alone at doses of 50 mumols/kg caused the increase of blood urea nitrogen (BUN) and urinary N-acetylglucosaminidase (NAG) and the degeneration of proximal tubule cells pathologically. The co-administration of Se, especially at doses of 20 mumols/kg/day, inhibited the increase of BUN and urinary NAG and depressed the degeneration of proximal tubule cells. The administration of CDDP at doses of 20 mumols/kg caused a mild reduction of transplanted Lewis lung carcinoma and a decrease of metastasis to lung. The co-administration of Se at doses of 8 mumols/kg didn't inhibit the antitumor effect of CDDP against Lewis lung carcinoma. Co-administration of Se didn't influence concentration of CDDP in plasma, blood cells, kidney and liver. In mice fed Se deficient diet, the nephrotoxicity of CDDP increased and activities of glutathione peroxidase (G-Px) in blood and kidney decreased. In mice co-administered with Se, G-Px activities didn't increase. These results suggest that co-administration of Se may allow use of CDDP at higher doses in cancer chemotherapy. Interaction between CDDP and Se differs from that between mercury and Se, and cadmium and Se(formation of compound). Intake of Se is related to appearance of the nephrotoxicity of CDDP. G-Px may be related to a part of the protective effect of Se on the nephrotoxicity of CDDP.
Araya
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First Department of Medicine, School of Medicine, Hokkaido University, Sapporo, Japan.
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D000970:Antineoplastic Agents; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity*; D004347:Drug Interactions; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D012643:Selenium / Q000493:pharmacokinetics / Q000494:pharmacology*; D018038:Sodium Selenite
D000970:Antineoplastic Agents; D000118:Acetylglucosaminidase; D012643:Selenium; D018038:Sodium Selenite; D002945:Cisplatin