Glutathione synthesis inhibitors

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. 

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). 

Previous evidence suggests that it is the change in the GSH/GSSG ratio rather than that in GSH levels as such that modulates insulin secretion buthionine-sulphoximine (BSO), an inhibitor of glutathione synthesis (Griffith and Meister, 1979), dramatically decreased islet GSH in rats when administered in vivo, but did not affect its GSH/GSSG ratio. Under these conditions, glucose-induced release of insulin was not affected (Klumpp and Ammon, 1988). 

Prostaglandin synthesis inhibitors Chemicals that alter cyclic nucleotide levels Glutathione... 

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],... 

In STZ-diabetic rat livers, the levels of mRNA of 1-gulonolactone oxidase, catalase, and glutathione peroxidase were decreased at 6 weeks, as well as that of plasma alpha 1 proteinase inhibitor 3.562 AA synthesis enzyme and recycling enzyme mRNAs were also decreased, as was the level of AA itself. It seems that the antioxidative defence system had been severely damaged. 

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