Although the effects of these cysteine precursors usually are attributed to enhanced GSH synthesis, they also are effective even when given in combination with a GSH-synthesis inhibitor (e.g., buthionine sulfoximine
) (Lailey et al.
Sasaki, "Enhancement of cisplatin toxicity by buthionine sulfoximine
, a glutathione-depleting agent, in mice," Research Communications in Chemical Pathology and Pharmacology, vol.
This was clearly demonstrated by a study in which primary cortical neurons treated with subtoxic levels of the GSH-depleting agent, buthionine sulfoximine
(BSO), underwent apoptosis in the presence of trace amounts of extracellular copper .
Chakraborty, "Fluoride-induced genotoxicity in mouse bone marrow cells: Effect of buthionine sulfoximine
and N-acetyl-l-cysteine," Journal of Applied Toxicology, vol.
In parallel, treatment of cells with glutathione synthesis inhibitor, buthionine sulfoximine
(BSO), was used as a positive control for GSH depletion (Supplementary Figure S1b).
Guan et al., "Isoliquiritigenin attenuates oxidative hepatic damage induced by carbon tetrachloride with or without buthionine sulfoximine
," Chemico-Biological Interactions, vol.
reported that injection of melatonin (4 mg/kg, ip) into newborn rats with developed cataracts by buthionine sulfoximine
as the inhibitor of glutathione synthesis decreased the incidence of cataract and increased the total glutathione levels significantly in the lens.
The contribution of redox imbalance in MAL-A induced cytotoxicity was confirmed by pre-incubating cells with an antioxidant, N-acetyl-L-cysteine (NAC) or a thiol depletor, buthionine sulfoximine
Levels of glutathione (GSH) in HepG2 and HepaRG and its depletion in response to treatment with buthionine sulfoximine
(BSO) were assessed using a luminescence-based assay performed according to manufacturer's instructions for adherent cell cultures, whereby tissue culture medium is removed from the cells prior to incubation of the cells with luminescent detection reagents.
Jimbow, "Selective in vivo accumulation of N-acetyl-4-S-cysteaminylphenol in B16F10 murine melanoma and enhancement of its in vitro and in vivo antimelanoma effect by combination of buthionine sulfoximine
," Cancer Research, vol.
"Shock and kill" effects of class I-selective histone deacetylase inhibitors in combina- tion with the glutathione synthesis inhibitor buthionine sulfoximine
in cell line models for HIV-1 quiescence.
And the inhibitor of de novo GSH synthesis, buthionine sulfoximine
, is known to be able to produce oxidative stress.