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

Roger Drew, John O. Miners

    Research output: Contribution to journalArticle

    182 Citations (Scopus)

    Abstract

    Buthionine sulphoximine (BSO) is an inhibitor of γ-glutamylcysteine synthetase (γ-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 γ-GCS and GSH were observed 2-4 hr after BSO administration; initial γ-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.

    Original languageEnglish
    Pages (from-to)2989-2994
    Number of pages6
    JournalBiochemical Pharmacology
    Volume33
    Issue number19
    DOIs
    Publication statusPublished - 1 Oct 1984

    Fingerprint Dive into the research topics of 'The effects of buthionine sulphoximine (BSO) on glutathione depletion and xenobiotic biotransformation'. Together they form a unique fingerprint.

  • Cite this