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Effect of oral glutathione on hepatic glutathione levels in rats and mice

Published online by Cambridge University Press:  09 March 2007

Jose Viña ,
Carmen Perez ,
Tadayasu Furukawa ,
Manuel Palacin  and
Juan R. Viña
Jose Viña
Affiliation:
Department of Physiology, University of Valencia, 46010-Valencia, Spain
Carmen Perez
Affiliation:
Department of Physiology, University of Valencia, 46010-Valencia, Spain
Tadayasu Furukawa
Affiliation:
Tokyo Research Laboratories, Kyowa Hakko Kogyo, Tokyo, Japan
Manuel Palacin
Affiliation:
Department of Biochemistry, Central University of Barcelona, Spain
Juan R. Viña
Affiliation:
Department of Biochemistry and Molecular Biology, University of Valencia, 46010-Valencia, Spain
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Abstract

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Administration of oral glutathione (GSH) increases hepatic GSH levels in fasted rats, in mice treated with GSH depletors such as diethyl maleate and in mice treated with high doses of paracetamol. An increase in hepatic GSH levels after administration of oral GSH does not occur in animals treated with buthionine sulphoximine, an inhibitor of GSH synthesis. Administration of oral GSH leads to an increase in the concentration of l-cysteine, a precursor of GSH, in portal blood plasma. Oral administration of l-methionine produced a significant decrease of hepatic ATP in fasted rats, but not in fed rats. Administration of N−acetylcysteine or GSH did not affect the hepatic ATP levels. The results show that the oral intake of GSH is a safe and efficient form of administration of its constituent amino acids in cases when GSH synthesis is required to replete hepatic GSH levels.

Keywords

GlutathioneLiverStarvationMiceRats
Type
Protein and Peptide Metabolism
Information
British Journal of Nutrition , Volume 62 , Issue 3 , November 1989 , pp. 683 - 691
Copyright
Copyright © The Nutrition Society 1989

References

REFERENCES

Anderson, M.E., Powrie, F., Puri, R.N. & Meister, A. (1985). Glutathione monoethyl ester: preparation, uptake by tissues, and conversion to glutathione. Archives of Biochemistry and Biophysics 239, 538–548.CrossRefGoogle ScholarPubMed
Beatty, P.W. & Reed, D.J. (1980). Involvement of the cystathionine pathway in the biosynthesis of glutathione by isolated rat hepatocytes. Archives of Biochemistry and Biophysics 204, 80–87.CrossRefGoogle ScholarPubMed
Boyland, E. & Chasseaud, L.F. (1967). Enzyme-catalysed conjugations of glutathione with unsaturated compounds. Biochemical Journal 104, 95–102.CrossRefGoogle ScholarPubMed
Chance, B., Sies, H. & Boveris, A. (1979). Hydroperoxide metabolism in mammalian organs. Physiological Reviews 59, 527–604.CrossRefGoogle ScholarPubMed
Estrela, J.M., Saez, G.T., Such, L. & Viña, J. (1983). The effect of l−cysteine and N−acetyl cysteine on rat liver glutathione (GSH). Biochemical Pharmacology 32, 3483–3485.CrossRefGoogle Scholar
Fahey, R.C. & Newton, G.L. (1983). Occurrence of low molecular weight thiols in biological systems. In Functions of Glutathione (Nobel Conference), pp. 251–260 [Larsson, A., Orrenius, S., Holmgren, A. and Mannervik, B., editors]. New York: Raven Press.Google Scholar
Furukawa, T., Meydani, S.N. & Blumberg, J.B. (1987). Reversal of age-associated decline in immune responsiveness by dietary glutathione supplementation in mice. Mechanisms of Ageing and Development 38, 107–117.CrossRefGoogle ScholarPubMed
Gaitonde, M.K. (1967). A spectrophotometric method for the direct determination of cysteine in the presence of other naturally occurring amino acids. Biochemical Journal 104, 627–633.CrossRefGoogle ScholarPubMed
Griffith, O.W. & Meister, A. (1979). Potent and specific inhibition of glutathione synthesis by buthionine sulfoximine (S-n-butyl homocysteine sulfoximine). Journal of Biological Chemistry 254, 7558–7560.CrossRefGoogle ScholarPubMed
Hahn, R., Wendel, A. & Flohé, L. (1978). The fate of extracellular glutathione in the rat. Biochimica et Biophysica Acta 539, 324–337.CrossRefGoogle ScholarPubMed
Hardwick, D.F., Applegarth, D.A., Cockcroft, D.M., Ross, P.M. & Calder, R.J. (1970). Pathogenesis of methionine-induced toxicity. Metabolism 19, 381–391.Google Scholar
Harper, A.E., Benevenga, N.J. & Wohlmueter, R.M. (1970). Effect of ingestion of disproportionate amounts of amino acids. Physiological Reviews 50, 428–558.Google Scholar
Hazelton, G.A. & Lang, C.A. (1980). Glutathione contents of tissues in the aging mouse. Biochemical Journal 188, 25–30.Google Scholar
Hinson, J.A., Mays, J.B. & Cameron, A.M. (1983). Acetaminophen-induced hepatic glycogen depletion and hyperglycemia in mice. Biochemical Pharmacology 32, 1979–1988.CrossRefGoogle ScholarPubMed
Keppler, D. & Decker, K. (1979). Glycogen determination with amyloglucosidase. In Methods of Enzymatic Analysis, pp. 1127–1131 [Bergmeyer, H.U., editor]. New York: Academic Press.Google Scholar
Kosower, N.S. & Kosower, E.M. (1978). The glutathione status of cells. International Review of Cytology 54, 109–160.CrossRefGoogle ScholarPubMed
Lamprecht, W. & Trautschold, I. (1979). Adenosine 5'-triphosphate determination with hexokinase and glucose-6-phosphate dehydrogenase. In Methods of Enzymatic Analysis, pp. 2101–2110 [Bergmeyer, H.U., editor]. New York: Academic Press.Google Scholar
Lauterburg, B.H., Corcoran, G.B. & Mitchell, J.R. (1983). Mechanism of action of N−acetylcysteine in the protection against the hepatotoxicity of acetaminophen in rats in vivo. Journal of Clinical Investigation 71, 980–991.CrossRefGoogle ScholarPubMed
Meister, A. & Anderson, M.E. (1983). Glutathione. Annual Review of Biochemistry 52, 711–760.CrossRefGoogle ScholarPubMed
Miners, J.O., Drew, R. & Birkett, D.J. (1984). Mechanism of action of paracetamol protective agents in mice in vivo. Biochemical Pharmacology 33, 2995–3000.CrossRefGoogle ScholarPubMed
Mitchell, J.R., Thorgeirsson, S.S., Potter, W.Z., Jollow, D.J. & Keiser, H. (1974). Acetaminophen-induced hepatic injury: protective role of glutathione in man and rationale for therapy. Clinical Pharmacology and Therapeutics 16, 676–684.CrossRefGoogle ScholarPubMed
Olney, J.W., Ho, O.L., Rhee, V. & Schainker, B. (1972). Cysteine-induced brain damage in infant and fetal rodents. Brain Research 45, 309–313.Google Scholar
Orrenius, S. & Moldéus, P. (1984). The multiple roles of glutathione in drug metabolism. Trends in Pharmacological Science 5, 432–435.Google Scholar
Prescott, L.F., Park, J., Ballantyne, A., Adriaenssens, P. & Proudfoot, A.T. (1977). Treatment of paracetamol (acetaminophen) poisoning with N−acetylcysteine. Lancet ii 432–434.Google Scholar
Puri, R.N. & Meister, A. (1983). Transport of glutathione, as gamma-glutamylcysteinylglycyl ester, into liver and kidney. Proceedings of the National Academy of Sciences, USA 80, 5258–5260.CrossRefGoogle ScholarPubMed
Racker, E. (1951). The mechanism of action of glyoxalase. Journal of Biological Chemistry 190, 685–696.CrossRefGoogle ScholarPubMed
Révész, L. & Edgren, M. (1982). Mechanism of radiosensitization and protection studied with glutathione-deficient human cell lines. In Progress in Radio-Oncology, vol. 2, pp. 235–242 [Kacher, K.H. and Kogelnik, H.D., editors]. New York: Raven Press.Google Scholar
Saez, G., Thornalley, P.J., Hill, H.A.O., Hems, R. & Bannister, J.V. (1982). The production of free radicals during the auto-oxidation of cysteine and their effect on isolated rat hepatocytes. Biochimica et Biophysica Acta 719, 24–31.CrossRefGoogle Scholar
Sakamoto, Y., Higashi, T. & Tateishi, N. (1983). Glutathione: Storage, Transport, and Turnover in Mammals, pp. 1–202. Tokyo: Japan Scientific Societies Press and Utrecht: VNU Science Press.Google Scholar
Smilkstein, M.J., Knapp, G.L., Kulig, K.W. & Rumack, B.H. (1988). Efficacy of oral N−acetylcysteine in the treatment of acetaminophen overdose. Analysis of the National Multicenter Study (1976 to 1985). New England Journal of Medicine 319, 1557–1562.Google Scholar
Tateishi, N., Higashi, T., Naruse, A., Nakashima, K., Shiozaki, H. & Sakamoto, Y. (1977). Rat liver glutathione: possible role as a reservoir of cysteine. Journal of Nutrition 107, 51–60.Google Scholar
Tateishi, N., Higashi, T., Shinya, S., Naruse, A. & Sakamoto, Y. (1974). Studies on the regulation of glutathione level in rat liver. Journal of Biochemistry, Tokyo 75, 93–103.CrossRefGoogle ScholarPubMed
Vale, J.A., Meredith, T.J. & Goulding, R. (1981). Treatment of acetaminophen poisoning. The use of oral methionine. Archives of Internal Medicine 141, 394–396.Google Scholar
Viña, J., Hems, R. & Krebs, H.A. (1978). Maintenance of glutathione content in isolated hepatocytes. Biochemical Journal 170, 627–630.Google Scholar
Viña, J., Romero, F.J., Estrela, J.M. & Viña, J.R. (1980). Effect of acetaminophen (paracetamol) and its antagonists on glutathione (GSH) content in rat liver. Biochemical Pharmacology 29, 1968–1970.CrossRefGoogle ScholarPubMed
Viña, J., Romero, F.J., Saez, G.T. & Pallardó, F.V. (1983 b). Effect of cysteine and N−acetyl cysteine on GSH content of brain of adult rats. Experientia 39, 164–165.Google ScholarPubMed
Viña, J., Sáez, G.T., Wiggins, D., Roberts, A.F.C., Hems, R. & Krebs, H.A. (1983 a). The effect of cysteine oxidation on isolated hepatocytes. Biochemical Journal 212, 39–44.CrossRefGoogle ScholarPubMed
Viña, J., Viña, J.R. & Sáez, G.T. (1986). Glutathione: metabolism and physiological functions. Life Chemistry Reports 4, 1–35.Google Scholar
Viña, J.R., Puertes, I.R., Rodriguez, A., Sáez, G.T. & Viña, J. (1987). Effect of physiological starvation on amino acid metabolism by lactating mammary gland. Studies in women and rats. Journal of Nutrition 117, 533–538.Google Scholar
Wendel, A. (1983). Hepatic lipid peroxidation: caused by acute drug intoxication, prevented by liposomal glutathione. International Journal of Clinical Pharmacological Research 3, 443–447.Google Scholar
Williamson, J.M. & Meister, A. (1981). Stimulation of hepatic glutathione formation by administration of l−2-oxothiazolidine-4-carboxylate, a 5-oxo-l−prolinase substrate. Proceedings of the National Academy of Sciences, USA 78, 936–939.Google Scholar