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.
D000818:Animals; D001711:Biotransformation; D019328:Buthionine Sulfoximine; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology; D002725:Chloroform / Q000633:toxicity; D003577:Cytochrome P-450 Enzyme System; D005978:Glutathione / Q000096:biosynthesis*; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D013438:Sulfhydryl Compounds; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D002725:Chloroform; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010105:Oxygenases; C027270:cytochrome P448-dependent mono-oxygenase; D005982:Glutathione Transferase; D005978:Glutathione