Enhancement of cisplatin toxicity by buthionine sulfoximine, a glutathione-depleting agent, in mice.
Pretreatment of buthionine sulfoximine (500 mg/kg, i.p., BSO), a potent glutathione-depleting agent, markedly increased the lethality and nephrotoxicity of cisplatin. These results suggest that a reactive electrophilic intermediate may be involved in the mechanism of cisplatin nephrotoxicity and moreover, that renal glutathione may play a protective role against cisplatin-induced nephrotoxicity.
Ishikawa
M
M
Department of Pharmacology and Toxicology, Tohoku College of Pharmacy, Sendai, Japan.
Takayanagi
Y
Y
Sasaki
K
K
D000818:Animals; D000963:Antimetabolites / Q000633:toxicity*; D001806:Blood Urea Nitrogen; D019328:Buthionine Sulfoximine; D002945:Cisplatin / Q000633:toxicity*; D004347:Drug Interactions; D005978:Glutathione / Q000378:metabolism*; D007674:Kidney Diseases / Q000139:chemically induced*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000633:toxicity; D051379:Mice; D008815:Mice, Inbred Strains
D000963:Antimetabolites; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005978:Glutathione; D002945:Cisplatin