GSH induction

Studies in rats have shown that acute doses of hydrazine cause hepatic steatosis accompanied by depletion of ATP and reduced glutathione (GSH) and hepatic accumulation of triglycerides. Biochemical effects from repeated exposure, however, included depletion of triglycerides and induction of nitrophe-nol hydroxylase activity in addition to changes in other microsomal enzymes. ... 

TCDD binds to the AhR and initiates a number of responses as well as induction of CYP1A1, including induction of UDP-glucuronosyl transferases, GSH transferases, and stimulation of apoptosis in thymocytes, resulting in thymic atrophy. 

As well as detoxication via reaction with GSH, the reactive 3,4-epoxide can be removed by hydration to form the dihydrodiol, a reaction that is catalyzed by epoxide hydrolase (also known as epoxide hydratase). This enzyme is induced by pretreatment of animals with the polycyclic hydrocarbon 3-methylcholanthrene, as can be seen from the increased excretion of 4-bromophenyldihydrodiol (Table 7.5). This induction of a detoxication pathway offers a partial explanation for the decreased hepatotoxicity of bromobenzene observed in such animals. A further explanation, also apparent from the urinary metabolites, is the induction of the form of cytochrome P-450 that catalyzes the formation of the 2,3-epoxide. This potentially reactive metabolite readily rearranges to 2-bromophenol, and hence there is increased excretion of 2-bromophenol in these pretreated animals (Table 7.5). 

In the course of another screening for the induction of GST activity in RL34 cells, MS-ITC was inadvertently isolated from wasabi as a potential inducer of GST. MS-ITC administered to rodents also showed both activities in vivo. As a result of elucidation of the platelet aggregation inhibition and the GST induction mechanisms of MS-ITC, the isothiocyanate moiety of MS-ITC plays an important role for antiplatelet and anticancer activities because of its high reactivity with sulfhydryl (RSH) groups in biomolecules (GSH, cysteine residue in a certain protein, etc.) (Figure 42.3). 

GSH has been proposed to be part of the thiol cycling in mammalian cells that may transduce oxidative stress redox signaling into the induction of many genes involved in proliferation, differentiation, and apoptosis [15], Studies with pure chemical systems have confirmed the reduction of V(V) maltol compounds by GSH or ascorbic acid [16], Putative glutathione transferase enzymes that bind vanadium have been isolated from an ascidian that accumulates vanadium in specialized cells to over 350 mM [17],... 

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