Abstract
Glutathione traps reactive intermediates of compounds such as acetaminophen and prevents their covalent binding to tissue macromolecules and their hepatotoxicity (Mitchell et al., 1973). The availability of glutathione for conjugate formation is, therefore, a critical determinant of the toxicity of electrophilic drug metabolites capable of alkylating nucleophilic sites on vital hepatic molecules. Indeed, depletion of glutathione by diethyl maleate leads to a striking increase in the extent of liver injury caused by such drug metabolites (Potter et al., 1974).
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Bartoli, G.M., and Sies, H.: Reduced and oxidized glutathione efflux from liver. Febs. Lett. 86: 89–91, 1978.
Griffith, O. W., Bridges, R. J., and Meister, A: Evidence that the a -glutamyl cycle functions in vivo using intracellular glutathione: Effects of amino acids and selective inhibition of enzymes. Proc. Natl. Acad. Sci. U.S.A. 75: 54055408, 1978.
Griffith, 0. W., and Meister, A.: Glutathione: interorgan translocation, turnover, and metabolism. Proc. Natl. Acad. ci. U.S.A. 76: 5606–5610, 1979.
Henriques, S. B., Henriques, O. B., and Mandelbaum, F. R.: Incorporation of glycine into glutathione and fibrinogen of rats under adrenaline treatment. Biochem. J. 66: 222–227, 1957.
Higashi, T., Tateishi, N., Naruse, A., and Sakamoto, Y.: Decrease of glutathione and induction of a-glutamyl transferase by dibutyryl–3’, 5’ cyclic AMP in rat liver. Biochem. Biophys. Res. Comm. 68: 1280–1286, 1976.
Higashi, T., Tateishi, N. Naruse, A., and Sakamoto, Y.: A novel physiological role of liver glutathione as a reservoir for L-cysteine. J. Biochem. (Tokyo) 83: 117–124, 1977.
Lauterburg, B. H., and Mitchell, J. R.: Increased hepatic glutathione (GSH) turnover following amino acid (AA) infusion: evidence for the function of the y-glutamyl-cycle in vivo. Gastroenterology 77: A24, 1979.
Lauterburg, B. H., Vaishnav, Y.,Stillwell, W. G., and Mitchell, J. R.: The effects of age and glutathione depletion on hepatic glutathione turnover in vivo determined by acetaminophen probe analysis. J. Pharmacol. Exp. Ther. 213: 5459, 1980a.
Lauterburg, B. H., and Mitchell, J. R.: Increased hepatic glutathione synthesis during fasting. Gastroenterology 78: A15, 1980b.
Leaf, G., and Neuberger, A: The effect of diet on the gluta- thione content of the liver. J. Biochem. 41: 280–287, 1947.
McLean, A. E. M., and Day, P. A.: The effect of diet on the toxicity of paracetamol and the safety of paracetamol-methionine mixtures. Biochem. Pharmacol. 24: 37–42, 1975.
Mitchell, J. R., Jollow, D. J., Potter, W. Z., Gillette, J. R., and Brodie, B. B.: Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione. J. Pharmacol. Exp. Ther. 187: 211–217, 1973.
Pessayre, D., Dolder, A. Artigou, J. Y., Wandscheer, J. C., Descatoire, V., DeGott, C., and Benhamou, J. P.: Effect of fasting on metabolite-mediated hepatotoxicity in the rat Gastroenterology 77: 264–271, 1979.
Potter, W. Z., Thorgeirsson, S. S., Jollow, D. J., and Mitchell, J. R.: Acetaminophen-induced hepatic necrosis. V. Correlation of hepatic necrosis, covalent binding and glutathione depletion in hamsters. Pharmacology (Basel) 12: 129143, 1974.
Richman, P. G., and Meister, A.: Regulation of y -glutamylcysteine synthetase by nonallosteric feedback inhibition by glutathione. J. Biol. Chem. 250: 1422–1426, 1975.
Tateishi, N., Higashi, T., Shinya, S., Naruse, A., and Sakamoto, Y.: Studies on the regulation of glutathione level in rat liver. J. Biochem. (Tokyo) 75: 93–103, 1974.
Waelsch, H., and Rittenberg, D.: Glutathione II. The metabolism of glutathione studied with isotopic ammonia and glutamic acid. J. Biol. Chem. 144: 53–58, 1942.
Young, L.: The metabolic conversion of naphthalene to 1:2dihydronaphthalene–1:2-diol. Biochem. 41: 417–422, 1947.
Zampaglione, N., Jollow, I. J., Mitchell, J. R., Stripp, B. Hamrick, M., and Gillette, J. R.: Role of detoxifying enzymes in bromobenzene–induced liver necrosis. J. Pharmacol. Exp. Ther. 187: 218–227, 1973.
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Lauterburg, B.H., Mitchel, J.R. (1982). In Vivo Regulation of Hepatic Glutathione Synthesis: Effects of Food Deprivation or Glutathione Depletion by Electrophilic Compounds. In: Snyder, R., et al. Biological Reactive Intermediates—II. Advances in Experimental Medicine and Biology, vol 136. Springer, New York, NY. https://doi.org/10.1007/978-1-4757-0674-1_34
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