Glutathione-5-transferase cytotoxicity

Procyanidin B2 (3) could induce the expression and activity of glutathione -transferase pi (GST pi), and the nuclear translocation of nuclear factor erythroid-derived 2 [Nfe2] of a transcription factor that in humans is encoded by the NFE2L2 gene. This nuclear factor erythroid-derived 2 [Nfe2] antioxidant response pathway is the primary cellular defense against the cytotoxic effects of oxidative stress by reactive oxygen species. 

Some of the sensitizing (and cytotoxic) effects of the nitro compounds can be attributed to GSH depletion. Activated chlorine maybe replaced by GS" [reaction (89) Wardman 1982 Stratford et al. 1983)], but the reaction is much more general. For example, the 2-nitroimidazoles react with GS by N02 release. These reactions are slow, but are considerably speeded up by glutathione-S-transferase (Wardman et al. 1973). 

Azathioprine [a zah THIO preen] has been the cornerstone of immunosuppressive therapy over the last several decades. It has a nitroimidazoloyl side chain attached to the sulfur of 6-mercap-topurine, which is removed by non-enzymatic reduction in the body by glutathione to yield 6-mercaptopurine (6-MP). The latter is then converted to the corresponding nucleotide, thioinosinic acid (TIMP), by the salvage pathway enzyme, hypoxanthine-gua-nine phosphoribosyl transferase. The immunosuppressant effects of azathioprine are due to this fraudulent nucleotide. (See pp. 380-381 for a discussion of 6-MP s mechanism of action, resistance, pharmacokinetics, and adverse effects.) Because of their rapid proliferation in the immune response, and their dependence on de novo synthesis of purines required for cell division, lymphocytes are predominantly affected by the cytotoxic effects of azathioprine. The drug has little effect on suppressing a secondary immune response. 

Epidemiological studies with dietary flavonoids have also demonstrated an inverse association with incidence of stroke (Rice-Evans 2001). Antitumour activity has been demonstrated in flavonoids. Nomilin in citrus induces glutathione-S-transferase (GST), which aids in detoxification of carcinogens. Quercetin inhibits cytotoxic... 

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