The effect of buthionine sulfoximine, an inhibitor of glutathione synthesis, on hepatic drug metabolism in the male mouse.

Buthionine sulfoximine significantly reduced the hepatic non-protein sulfhydryl (NPSH) content of male B6C3F1 mice within 2 h after intraperitoneal (i.p.) injection. This treatment did not affect the activity of several hepatic microsomal and cytosolic enzymes responsible for xenobiotic metabolism. Pretreatment of mice with buthionine sulfoximine (2 mmol/kg) increased the hepatotoxicity of chloroform, but did not affect the hepatotoxicity of carbon tetrachloride. These findings suggest that buthionine sulfoximine can be a useful agent for studying the role of glutathione (GSH) in hepatic biotransformation of xenobiotics.