Buthionine sulfoximine

Mizutani, T. Satoh, K. Nomura, H. Nakanishi, K. Hepatotoxicity of eugenol in mice depleted of glutathione by treatment with DL-buthionine sulfoximine. Res. Commun. Chem. Pathol. Pharmacol. 1991, 71, 219-230. 

Mizutani T, Nakohori Y, Yamamoto K. 1994. p-Dichlorobenzene-induced hepatotoxicity in mice depleted of glutathione by treatment with buthionine sulfoximine. Toxicol 94 57-67. 

VOLUME STRAIN BUNDLING PROTEIN BUNNETT-OLSEN EQUATIONS COX-YEATS EQUATION ACIDITY FUNCTION BURST KINETICS Buthionine sulfoximine,... 

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-... 

Inhalation exposure of male B6C3Fi mice to dichloromethane (6 h, once) led to vacuolation of bronchiolar cells at exposure levels > 2000 ppm [6940 mg/m ], while no effect was obsened at levels < 1000 ppm [3470 mg/m (Foster et al., 1994). Pretreatment with the cytochrome P450 inhibitor piperonyl butoxide (300 mg/kg intraperi-toneally) 1 h before the exposure practically abolished the toxic effect upon bronchiolar cells, while buthionine sulfoximine (1 g/kg intraperitoneally), which decreased the pulmonary glutathione content by 50%, had no such protective effect. In Clara cells isolated after exposure to dichloromethane exposure (> 1000 ppm), the proportion of cells in tlie S-phase was increased. 

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). 

Osterloh, J. Xiwen, H. (1990) Effects of 1,3-dichloropropene on the kidney of Fisher 344 rats after pretreatment with diethyl maleate, buthionine sulfoximine, and aminooxyacetic acid. J. Toxicol, environ. Health, 28, 247-255... 

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). 

Normal catabolism of MG is largely dependent on availability of cellular GSH and activities of GSH-related enzymes, including GSH-Px and GSH-Red. Malfunction of the GSH system could potentially evoke cellular damage. For instance, treating normotensive rats with buthionine sulfoximine (BSO) for 2 weeks has been reported to decrease cellular GSH by 70% and to induce hypertension (Vaziri et al. 2000). In addition, reduction of intracellular GSH level by BSO resulted in sustained and reversible narrowing of rat femoral arteries (Zhou et al. 1996). We showed increased MG level with decreased GSH and lower activities of GSH-Red and GSH-Px in aortic VSMC from 13-week-old SHR compared to those from normotensive WKY rats (Wu and Juurlink 2002). The question that remains to be answered is whether increased cellular MG level is the key link between an impaired GSH pathway and essential hypertension. We recently observed elevated levels of MG in plasma or the aorta and MG-induced CEL and CML in the aorta of SHR as early as 8 weeks of age. These changes preceded decreased GSH level (Table 10.2) and... 

The effect of glutathione-depleting agents on the amounts of cellular chromium(in) and chromium(V) was determined in Chinese hamster V-79 cells treated with sodium chromate (Sugiyama and Tsuzuki 1994). Buthionine sulfoximine at 25 pM reduced glutatione levels to about 1% of control values, and increased chromium(V) levels by about 67%. The total chromium uptake was decreased by about 20%, and chromium(III) levels were decreased by 20%. Diethylmaleate (1 mM) decreased glutathione levels less than 1%, decreased chromium(V) levels by 27%, and chromium(in) levels by 31%. However, the... 

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. 

Slott V, Hales BF. 1985. Effect of glutathione (GSH) depletion by buthionine sulfoximine (BSO) on the in vitro teratogenicity and embryolethality of acrolein (AC). Teratology 31 33A. 

Mayer RD, Lee KE, and Cockett AT. Inhibition of cisplatin-induced nephrotoxicity in rats by buthionine sulfoximine, a glutathione synthesis inhibitor. Cancer Chemotherapy and Pharmacology 20 207-210,1987. 

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]. 

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