L-buthionine sulfoximine

Romero FJ, Sies FI (1984) Subcellular glutathione contents in isolated hepatocytes treated with L-buthionine sulfoximine. Biochem Biophys Res Commun 123 1116-1121 Romieu A, Gasparutto D, Cadet J (1999a) Synthesis and characterization of oligonucleotides containing 5, 8-cyclopurine 2 -deoxyribonucleosides (5 R)-5, 8-cyclo-2 -deoxyadenosine, (5 S)-5, 8-cyclo-2 -deoxyguanosine and (5 R)-5, 8-cyclo-2 -deoxyguanosine. Chem Res Toxicol 12 412-421... 

Male BALB/c mice exposed to ozone (1.2 mg m 10 hr per day) showed decreased TAC of blood serum (by 26% on day 5) (F7). Oxidant stress in vivo elicited by injections of L-buthionine sulfoximine (inhibitor of glutathione biosynthesis), hydroquinone, and triethylenetetraamine reduced TAC of rat blood plasma (LI). 

In a study of six mercury compounds, mercury chloride, mercury nitrate, sodium ethylmercurithi-osalicylate, methyl mercury chloride, mercury acetate and phenylmercury acetate in MDCK cells, LLC-PKl cells and human primary proximal tubular cells (hPTC) and non-renal cell lines (SAOS and Hep G2) it was found that all mercury compounds were toxic to all cell types as evidenced by neutral red uptake, thymidine incorporation and the MTT assay [189]. However, sodium ethylmercurithiosalicylate, methyl mercury chloride and phenylmercury acetate were one order of magnitude more toxic than the other compounds. In addition the GSH synthesis inhibitor L-buthionine sulfoximine (BSO) potentiated the toxicity of all mercury compounds [189]. In a study using primary rabbit proximal tubular cells it was also shown that methyl mercury chloride is more toxic than mercury chloride [190]. Differences in the extent and rate of metal uptake were also evident. Maximum cellular uptake of Hg " occurred within 6-24 hr after exposure and was not concentration-dependent, whereas maximum uptake of CHgHg" occurred within 3 hr of exposure and was concentration- dependent [190]. 

FIGURE 16.12 Chemical structure for L-buthionine sulfoximine (L-BSO) and L-theanine. 

Pileblad, E., Miagnusson, T. and Fornstedt, B. (1991) Reduction of brain glutathione by L-buthionine sulfoximine potentiates the dopamine-depleting action of 6-hydroxydopamine in rat striatum. J. Neurochem. 52 978-980. 

Sipos EP, Witham TF, Ratan R, Burger PC, Baraban J, Li KW, Piantadosi S, Brem H. L-buthionine sulfoximine potentiates the antitumor effect of 4-hydroperoxycyclophosphamide when administered locally in a rat glioma model. Neurosurgery 2001 48 392-400. 

We have further investigated the dependency of HC "NO synthesis on cellular GSH levels and BH4 availability. Inhibition of GSH synthesis using the 7-glutamylcysteine synthetase inhibitor buthionine sulfoximine, which blocks de novo GSH synthesis, markedly reduced GSH levels in cultured HC, approximately 5% of control, but resulted in only a 40-50% reduction in NO2 biosynthesis in response to cytokines and LPS. More effective was the inhibition of GSH reductase with l,3-bis(chloroethyl)-l-nitrosurea, which prevents the recycling of GSSH back to GSH. GSH levels also fell in these cells, but a marked decrease in NO2" formation was seen, suggesting that GSH recycling was an important aspect of -NO formation. Similar results had been reported for con-... 

On the other hand, hydroquinone (3 pmol/L) prevented the staurosporine-induced apoptosis of HL-60 and the IL-3-dependent murine myeloblastic (32D) cell line it also prevented apoptosis of the 32D cells observed in the absence of IL-3. The myeloperoxidase inhibitor indomethacin opposed the effect of hydroquinone on staurosporine-induced apoptosis of HL-60 cells (Hazel et al., 1995, 1996b). Pretreatment of human leukaemia cells ML-1 with buthionine sulfoximine (100 pmol/L for 24 h), in order to decrease their glutathione content, increased the susceptibility of these cells to hydroquinone-induced inhibition of differentiation caused by phorbol acetate pretreatment with l,2-dithiole-3-thione, which induces reduced glutathione synthesis, prevented the differentiation inhibition of hydroquinone. Treatment of DBA/2 mice with 1,2-dithiole-3-thione, which increased the activity of quinone reductase of bone-marrow stromal cells by 50%, decreased the susceptibility of these cells towards hydroquinone (Trush et al., 1996). 

As noted above, the X-ray sensitization of cells using MGd has been investigated extensively and appears to operate at least in part in an oxygen dependent manner, with cytotoxic activity that is substantially enhanced upon the addition of ascorbate to the media [69], The cytotoxic activity of MGd can also be enhanced with L-buthionine-S,R-sulfoximine (BSO), an irreversible inhibitor of an enzyme involved in glutathione biosynthesis (y-glutamylcysteine synthetase), that serves to suppress the synthesis of ROS-protective glutathione. Presumably, this activity is responsible for the in vitro radiation enhancing effect of BSO [66,71],... 

Bhatia, K., Kaur, M., Atif, F., Ali, M., Rehman, H., Rahman, S. and Raisuddin, S. (2006) Aqueous extract of Trigonella foenum-graecum L. ameliorates additive urotoxicity of buthionine sulfoximine and cyclophosphamide in mice. Food and Chemical Toxicology 44, 1 744-1 750. 

C8H18N203S L-buthionine-(S,R)-sulfoximine 83730-53-4 25.00 1.1249 2 15787 C9H4CI3IO 3-iodo-2-propynyl-2,4,5-trichlorophenyl ether 777-11-7 25.00 1.9350 2... 

It should be noted that L-BSO (buthionine sulfoximine) is a strong inhibitor against y-glutamylcysteine synthetase, the enzyme that catalyzes the first reaction of glutathione (GSH) biosynthesis. L-BSO has been accepted as an anticancer medicine. ... 

However, if GSH is compromised in vivo by administration of its antimetabolite, L-buthionine-(S,/ )-sulfoximine, ascorbate is utilized to protect against cell damage due to GSH deficiency (Martensson and Meister, 1991). If enzymatic or non-enzymatic antioxidants are inactivated or depleted, ROS can trigger various deleterious events, including oxidation of lipids, proteins and nucleic acid bases, as described in the next section. 

OHEi(E2) and 2-methoxyEi(E2) (C8). If the hamsters were injected with L-buthionine (S, K) sulfoximine to deplete the cellular levels of GSH, followed by E2 2.5 h later, the GSH conjugates were virtually nondetectable in both the liver and kidney, but the kidney now had detectable levels of the... 

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