Selenium-induced protection against cis-diamminedichloroplatinum(II) nephrotoxicity in mice and rats.
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.
Baldew
G S
GS
Department of Radiochemistry, Interfaculty Reactor Institute, Delft, The Netherlands.
van den Hamer
C J
CJ
Los
G
G
Vermeulen
N P
NP
de Goeij
J J
JJ
McVie
J G
JG
D000818:Animals; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D003404:Creatinine / Q000097:blood; D004347:Drug Interactions; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008099:Liver / Q000187:drug effects; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000008:administration & dosage / Q000494:pharmacology*
D003404:Creatinine; D012643:Selenium; D002945:Cisplatin