Increased Biliary Glutathione Disulfide (GSSG) Release in Chronically Ethanol-Treated Rats

  • Osvaldo R. Koch
  • Elba Martino
  • Alberto Boveris
  • Helmut Sies


Recently, we have reported the observation of a substantial increase in biliary glutathione disulfide (GSSG) concentration in chronically ethanol-treated rats as compared to isocalorically pair-fed controls (Sies et al., 1979). Such information may be relevant to the discussion of liver damage related to chronic alcohol intake. The long-standing dispute in the literature regarding the occurrence of lipid peroxidation in alcoholism (cf. Plaa & Witschi, 1976) may become resolved when experimental approaches of non-invasive and non-destructive nature become increasingly employed. In this respect, GSSG release into bile may prove to be a particularly useful tool, complementing the method of measurement of alkane exhalation (Riely et al., 1974; Köster et al., 1977; Litov et al., 1978) and the new developments in the detection of ultraweak chemiluminescence (cf. Chance et al., 1978, for an overview).


Bile Flow Chronic Ethanol Butyl Hydroperoxide Chronic Alcohol Intake Hepatic Lipid Peroxidation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bartoli, G. M. and Sies, H., 1978, Reduced and oxidized glutathione efflux from liver, FEBS Lett., 86: 89.Google Scholar
  2. Burk, R. F., Nishiki, K., Lawrence, R. A. and Chance, B., 1978, Peroxide remóval by selenium-dependent glutathione peroxidases in hemoglobin-free per-fused rat liver, J. Biol. Chem., 253:43.Google Scholar
  3. Chance, B., Boveris, A., Nakase, Y. and Sies, H., 1978, Hydroperoxidemetabolism: an overview, in: Functions-of Glutathione in Liver and Kidney, H. Sies, A. Wendel, eds., Springer Verlag, Heidelberg, New York.Google Scholar
  4. Chance, B., Sies, H. and Bovers, A., 1979, Hydroperoxide metabolism in mammalian organs, Phÿsiol. Rev., 59:527.Google Scholar
  5. Forker, E. L., 1977, Mechanisms of hepatic bile formation, Ann. Rev. Physiol., 39:323.Google Scholar
  6. Lawrence, R. A. and Burk, R. F., 1976, Glutathione peroxidase activity in selenium-deficient rat liver, Biochem. Biophys. Res. Comm., 71:952.Google Scholar
  7. Levine, W. G., 1978, Biliary excretion of drug and other xenobiotics, Ann. Rev. Pharmacol. Toxicol., 18:81.Google Scholar
  8. Litov, R. E., Irving, D. H., Downey, J. E. and Tappel, A. L., 1978,Google Scholar
  9. Lipid peroxidation: a mechanisms involved in actue ethanol toxicity as demonstrated by in vivo pentane production in the rat, Lipids, 13:305.Google Scholar
  10. Koch, O. R., Bedetti, C. D., Gamboni, M., Montero, G. A. and Stoppani,Google Scholar
  11. A. 0. M., 1976, Functional alterations of liver mitochondria in chronic experimental alcoholism, Exp. Mol. Pathol., 25:253.Google Scholar
  12. Koch, O. R., Bartoli, G. M. and Galeotti, T., 1978, Aumento de la lipoperoxidacion hepatica izdúcida por el consumo cronico de etanol, Medicina (Buenos Aires), 38: 779.Google Scholar
  13. Köster, U., Albrecht, D. and Kappus, H., 1977, Evidence for carbon tetrachloride-, and ethanol-induced lipid peroxidation in vivo demonstrated by ethane production in mice and rats, Toxicol. Appt. Pharmacol., 41:639.Google Scholar
  14. McDonald, C. N., 1973, The effects of ethanol on hepatic lipid peroxidation and on the activities of glutathione reductase and peroxidase, FEES Lett., 35: 227.Google Scholar
  15. Morland, J., Flengsrud, R., Prydz, H. and Svendsen, L., 1979, Hepatic amino acid levels in rats after longterm ethanol feeding, Biochem. pharmacol., 28: 423.Google Scholar
  16. Nishiki., K., Jamieson, D., Oshino, N. and Chance, B., 1976, Oxygen toxicity in the perfused: rat liver and lung under hyperbaric conditions, Biochem. J., 160:343.Google Scholar
  17. Oshino, N. and Chance, B., 1977, Properties of glutathione release observed during reduction of organic hydroperoxide, demethylation of aminopyrine and oxidation of some substances in perfused rat liver, and their Implications for the physiological function of catalase, Biochem. J., 162; 509.Google Scholar
  18. Owens, C. W. and Belcher, R. V., 1965, A colorimetric micro-method for the determination of glutathione, Biochem. J., 94: 705.Google Scholar
  19. Plea, G. L. and Witschi, H., 1976, Chemicals, drugs, and lipid peroxidation, Ann. Rev. Pharmacol. Toxìcol., 16:125.Google Scholar
  20. Reitz, R. C., 1975, A possible mechanism for the peroxidation of lipids due to chronic ethanol ingestion, Biochim. Biophys. Acta, 380:145.Google Scholar
  21. Sies, H., 1979, Giutathïone redox state and the efflux of GSSG and GSH from the hepatocyte, Kith iUB Meeting, Toronto, 06-8-R67.Google Scholar
  22. Sies, H., Gerstenecker, C., Menzel, H. and Flohe, L., 1972, Oxidation in the NADP-system and release of GSSG from hemoglobin-free perfused rat liver during peroxidatic oxidation of glutathione by hydroperoxides, FEBS Lett., 27: 171.Google Scholar
  23. Sies, H. and Summer, K. H., 1975, Hydroperoxide-metabolizing systems in rat liver, Eur. J. Biochem., 57:503.Google Scholar
  24. Sies, H.,Bartoli, G. M., Burk, R. F. and Waydhas, C., 1978a, Glutathione efflux from perfused rat liver after phenobarbital treatment,durng drug oxidations, and in selenium deficiency, Eur. J. Biochem., 89:113.Google Scholar
  25. Sies, H., Wählländer, A…, Linke, I. and Marklstorfer, A., 1978b, Glutathione disulfide •(IGSSG) efflux from liver occurs via excretion into bile, Hoppe-Seylers Z. Physiol. Chem., 359:1151.Google Scholar
  26. Sies, H., Wahlländer, A. and Waydhas, C., 1978c, Properties of glutathione disulfide ÇGSSGI and glutathione-S-conjugate release from perfused rat liver, in: Functions of Glutathione in Liver and Kidney H. Sies, A.. Wendel. eds., Springer Verlag, Heidelberg, New York.CrossRefGoogle Scholar
  27. Sies, H., Koch, O. R., Martino, E. and Boveris, A., 1979, Increased biliary glutathione disulfide (SSG) release in chronically ethanol-treated rats, FEES Lett., 103: 287.Google Scholar
  28. Stege, T. E., Hanby, J. D. and Di Luzio, N.R., 1977, Acetaldehyde-induced Hepatic Lipid Peroxidation, 139-160, in: Currents in Alcoholism: Biological, Biomedical and Clinical Studies F. A. Sexas, ed., Grune and Stratton, New York.Google Scholar
  29. Thurman, R., 1973, Induction of hepatic microsomal reduced nicotinamide adenine dinucleotide phosphate-dependent production of hydrogen peroxide by chronic prior treatment with ethanol, Mol. Pharmacol., 9:670.Google Scholar
  30. Tietze, F., 1969, Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues, Anal. Bochem.27:502.Google Scholar

Copyright information

© Springer Science+Business Media New York 1980

Authors and Affiliations

  • Osvaldo R. Koch
    • 1
  • Elba Martino
    • 2
  • Alberto Boveris
    • 2
  • Helmut Sies
    • 3
  1. 1.Centro de Patologia Experimental, II Catedra de PatologiaUniversidad de Buenos AiresBuenos AiresArgentina
  2. 2.Instituto de Quimica BiologicaUniversidad de Buenos AiresBuenos AiresArgentina
  3. 3.Institut für Physiologische Chemie, Physikalische Biochemie und ZellbiologieUniversität MünchenMünchenGermany

Personalised recommendations