The effects of buthionine sulphoximine (BSO) on glutathione depletion and xenobiotic biotransformation

Biochem Pharmacol. 1984 Oct 1;33(19):2989-94. doi: 10.1016/0006-2952(84)90598-7.


Buthionine sulphoximine (BSO) is an inhibitor of gamma-glutamylcysteine synthetase (gamma-GCS) and, consequently lowers tissue glutathione (GSH) concentrations. In fed male C3H mice, liver and kidney GSH levels were depleted by BSO in a dose dependent manner with maximum effect (35% of initial levels) occurring with doses between 0.8 and 1.6 g/kg, i.p. At these doses maximum effects on gamma-GCS and GSH were observed 2-4 hr after BSO administration; initial gamma-GCS activity and GSH content were restored approximately 16 hr post BSO. BSO, either in vivo or in vitro, had no effect on hepatic microsomal cytochrome P-450 levels, a range of cytochrome P-450 dependent enzyme activities or p-nitrophenol glucuronyl transferase activity. Similarly, BSO had no effect on phenol sulphotransferase and two GSH-transferase activities in the 105,000 g supernatant fraction. BSO had no effect on the duration of hexobarbitone induced narcosis in mice. Consistent with specific inhibition of GSH synthesis, BSO pretreatment of mice decreased the proportion of a 50 mg/kg dose of paracetamol excreted in the urine as GSH-derived conjugates but did not affect paracetamol clearance through the glucuronidation or sulphation pathways. Since BSO does not affect cytochrome P-450 or conjugating enzyme activity, its use as a specific depletor of tissue GSH in the investigation of mechanisms of xenobiotic-induced toxicities is preferable to the standard GSH-depleting agents as these have other enzymic effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / metabolism
  • Animals
  • Biotransformation
  • Buthionine Sulfoximine
  • Glutamate-Cysteine Ligase / antagonists & inhibitors
  • Glutathione / analysis*
  • Glutathione / metabolism
  • In Vitro Techniques
  • Male
  • Methionine Sulfoximine / analogs & derivatives*
  • Methionine Sulfoximine / pharmacology
  • Mice
  • Mice, Inbred C3H


  • Methionine Sulfoximine
  • Acetaminophen
  • Buthionine Sulfoximine
  • Glutamate-Cysteine Ligase
  • Glutathione