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.