Amino Acids

, Volume 15, Issue 1–2, pp 53–76 | Cite as

Taurine: Protective properties against ethanol-induced hepatic steatosis and lipid peroxidation during chronic ethanol consumption in rats

  • M. D. J. Kerai
  • Catherine J. Waterfield
  • S. H. Kenyon
  • D. S. Asker
  • J. A. Timbrell
Full Papers


Alcohol was administered chronically to female Sprague Dawley rats in a nutritionally adequate totally liquid diet for 28 days. This resulted in hepatic steatosis and lipid peroxidation. Taurine, when co-administered with alcohol, reduced the hepatic steatosis and completely prevented lipid peroxidation. The protective properties of taurine in preventing fatty liver were also demonstrated histologically. Although alcohol was found not to affect the urinary excretion of taurine (a non-invasive marker of liver damage), levels of serum and liver taurine were markedly raised in animals receiving alcohol + taurine compared to animals given taurine alone. The ethanol-inducible form of cytochrome P-450 (CYP2E1) was significantly induced by alcohol; the activity was significantly lower than controls and barely detectable in animals fed the liquid alcohol diet containing taurine. In addition, alcohol significantly increased homocysteine excretion into urine throughout the 28 day period of ethanol administration; however, taurine did not prevent this increase. There was evidence of slight cholestasis in animals treated with alcohol and alcohol + taurine, as indicated by raised serum bile acids and alkaline phosphatase (ALP). The protective effects of taurine were attributed to the potential of bile acids, especially taurine conjugated bile acids (taurocholic acid) to inhibit the activity of some microsomal enzymes (CYP2E1). Thesein vivo findings demonstrate for the first time that hepatic steatosis and lipid peroxidation, occurring as a result of chronic alcohol consumption, can be ameliorated by administration of taurine to rats.


Amino acids Taurine Ethanol Protection Hepatic steatosis Lipid peroxidation CYP2E1 Homocysteine Methionine synthase 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Albano E, Tomasi E, Persson J-O, Terelius Y, Goria-Gatti L, Ingelman-Sundberg M, Dianzani MU (1991) Role of ethanol-inducible cytochrome P-450 (P-4502E1) in catalyzing the free radical activation of aliphatic alcohols. Biochem Pharm 41: 1895–1902Google Scholar
  2. Bradford MM (1976) A rapid and sensitive method for quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254Google Scholar
  3. Butler WM, Maling HM, Horning HG, Brodie BB (1962) The direct determination of liver triglycerides. J Lipid Res 2: 95–96Google Scholar
  4. Chen J, Farrell GC (1996) Bile acids produce a generalized reduction of the catalytic activity of cytochromes P-450 and other hepatic microsomal enzymes in vitro: relevance to drug metabolism in experimental cholestasis. J Gastroenterol Hepatol 11: 870–877Google Scholar
  5. Chen J, Murray M, Liddle C, Jiang XM, Farrell GC (1995) Downregulation of malespecific cytochrome P-450s 2C11 and 3A2 in bile duct-ligated male rats: importance to reduced hepatic content of cytochrome P-450 in cholestasis. Hepatology 22: 580–587Google Scholar
  6. De Master EG, Redfern B (1987) High performance liquid chromatography of hepatic thiols with electrochemical detection. In: Jakoby WB, Griffith OW (eds) Methods of enzymology, vol 193. Academic Press, New York, pp 110Google Scholar
  7. Ekstrom G, Ingelman-Sundberg M (1989) Rat liver microsomal NADPH-supported oxidase activity and lipid peroxidation dependent on ethanol-inducible cytochrome P-450 (P-4502E1). Biochem Pharm 38: 1313–1319Google Scholar
  8. Ellman GL (1959) Tissue sulphydryl groups. Arch Biochem Biophys 82: 70–77Google Scholar
  9. Farinati F, Lieber CS, Garro AJ (1989) Effects of chronic ethanol consumption on carcinogen activating and detoxifying systems in rat upper alimentary tract tissue. Alcohol Clin Exp Res 13: 357–360Google Scholar
  10. Fernández-Checa JC, Hirano T, Tsukamoto H, Kaplowitz N (1993) Mitochondrial glutathione depletion in alcoholic liver disease. Alcohol 10: 469–475Google Scholar
  11. Fortin L-J, Genest J (1995) Measurement of homocysteine in the prediction of arteriosclerosis. Clin Biochem 28: 155–162Google Scholar
  12. Fukaya Y, Senda N, Fujita A, Imai S, Sawada I (1996) Combined effect of taurine and ox bile on biliary flow. Adv Exp Med Biol 403: 93–97Google Scholar
  13. Griffith OW (1980) Determination of glutathione and glutathione disulphide using glutathione reductase and 2-vinylpyridine. Anal Biochem 106: 207–212Google Scholar
  14. Harrison DJ, Burt AD (1993) Pathology of alcoholic liver disease. Bailliere's Clinical Gastroenterol 7: 641–662Google Scholar
  15. Horning MG, Wakabayashi M, Maling HM (1963) Biochemical processes involved in the synthesis, accumulation and release of triglycerides by the liver. In: Horning EC (ed) Mode of action of drugs. Effects of drugs on synthesis and mobilization of lipids, vol 2. Pergamon, Oxford, p 13Google Scholar
  16. Huxtable RJ (1992) Physiological actions of taurine. Physiol Rev 72: 101–163Google Scholar
  17. Jenner AM, Timbrell JA (1994) Effect of acute and repeated exposure to low doses of hydrazine on hepatic microsomal enzymes and biochemical parameters in vivo. Arch Toxicol 68: 240–245Google Scholar
  18. Kawase T, Kato S, Lieber CS (1989) Lipid peroxidation and antioxidant defense systems in rat liver after chronic ethanol feeding. Hepatology 10: 815–821Google Scholar
  19. Kawata S, Imai Y, Inada M, Tamura S, Miyoshi S, Nishikawa M, Minami Y, Tarui S (1987) Selective reduction of hepatic cytochrome P-450 content in patients with intrahepatic cholestasis. A mechanism for impairment of microsomal drug oxidation. Gastroenterol 92: 299–303Google Scholar
  20. Kenyon SH, Nicolaou A, Gibbons WA (1998) The effect of ethanol and its metabolites upon methionine synthase activity in vitro. Alcohol 15: 305–309Google Scholar
  21. Lake BG (1987) Investigations and characterization of microsomal fractions for studies of xenobiotic metabolism. In: Snell K, Mullock B (eds) Biochemical toxicology: a practical approach. IRL Press, Oxford, pp 183–215Google Scholar
  22. Lieber CS (1993) Biochemical factors in alcoholic liver disease. Semin Liver Dis 13: 136–153Google Scholar
  23. Lieber CS (1997a) Cytochrome P-4502E1: its physiological and pathological role. Physiol Rev 77: 517–544Google Scholar
  24. Lieber CS (1997b) Role of oxidative stress and antioxidant therapy in alcoholic and nonalcoholic liver diseases. Adv Pharmacol 38: 601–628Google Scholar
  25. Lieber CS, DeCarli LM (1989) Liquid diet technique of ethanol administration: 1989 update. Alcohol Alcohol 24: 197–211Google Scholar
  26. Lieber CS, Savolainen M (1984) State of the art. Ethanol and lipids. Alcoholism Clin Exp Res 8: 409–423Google Scholar
  27. Lieber CS, Casini A, DeCarli LM, Kim C, Lowe N, Sasaki R, Leo MA (1990) S-adenosylL-methionine attenuates alcohol-induced liver injury in the baboon. Hepatology 11: 165–172Google Scholar
  28. Lieber CS, Robins SJ, Li J., DeCarli LM, Mak KM, Faulo JM, Leo MA (1994) Phosphatidylcholine protects against fibrosis and cirrhosis in the baboon. Gastroenterol 106: 152–159Google Scholar
  29. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 263: 265–275Google Scholar
  30. McCloskey LP, Mahaney P (1981) An enzymatic assay for acetaldehyde in grape juice and wine. Am J Enol Vitic 32: 159–162Google Scholar
  31. Morimoto M, Hagbövrk A-L, Nanji AA, Ingelman-Sundberg M, Lindros KO, Fu PC, Albano E, French SW (1993) Role of cytochrome P-4502E1 in alcoholic liver disease pathogenesis. Alcohol 10: 459–464Google Scholar
  32. Müller A, Sies H (1982) Role of alcohol dehydrogenase activity and of acetaldehyde in ethanol-induced ethane and pentane production by isolated perfused rat liver. Biochem J 206: 153–156Google Scholar
  33. Nakashima T, Takino T, Kuriyama K (1983) Therapeutic and prophylactic effects of taurine administration on experimental liver injury. In: Kuriyama K, Huxtable RJ, Iwata H (eds) Sulphur amino acids: biochemical and clinical aspects. Alan R Liss Inc., New York, pp 449–459Google Scholar
  34. Nicolaou A, Waterfield CJ, Kenyon SH, Gibbons WA (1997) The inactivation of methionine synthase in isolated rat hepatocytes by sodium nitroprusside. Eur J Biochem 244: 876–882Google Scholar
  35. Omura T, Sato R (1964) The carbon monoxide binding pigment of liver microsomes. Evidence of its haemoprotein value. J Biol Chem 239: 2370–2378Google Scholar
  36. Pietrzak ER, Shanley BC, Kroon PA (1995) Antibodies made against a formaldehydeprotein adduct cross react with an acetaldehyde-protein adduct. Implications for the origin of antibodies in human serum which recognize acetaldehyde-protein adducts. Alcohol Alcohol 30: 373–378Google Scholar
  37. Prough RA, Burke MD, Mayer RT (1978) In: Fleischer S, Packer L (eds) Methods in enzymology, vol 52. Academic Press, New York, pp 372–377Google Scholar
  38. Reinke LA, Lai EK, DuBose CM, McCay PB (1987) Reactive free radical generation in vivo in heart and liver of ethanol-fed rats: correlation with radical formation in vitro. Proc Natl Acad Sci USA 84: 9223–9227Google Scholar
  39. Sawicki E, Stanley TW, Johnson H (1963) Comparison of spectrophotometric and spectrophotofluorometric methods for the determination of malonaldehyde. Anal Chem 35: 199–205Google Scholar
  40. Schapiro RH, Scheig RL, Drummey GD, Mendelson JH, Isselbacher KJ (1965) Effect of prolonged ethanol ingestion on the transport and metabolism of lipids in man. N Engl J Med 272: 610Google Scholar
  41. Seabra V, Timbrell JA (1997) Modulation of taurine levels in the rat liver alters methylene dianiline hepatotoxicity. Toxicology 122: 193–204Google Scholar
  42. Shaw S, Jayatilleke E, Ross WA (1981) Ethanol-induced lipid peroxidation: potentiation by long-term alcohol feeding and attenuation by methionine. J Lab Clin Med 98: 417–424Google Scholar
  43. Shaw S, Jayatilleke E, Lieber CS (1988) Lipid peroxidation as a mechanism of alcoholic liver injury: role of iron mobilization and microsomal induction. Alcohol 5: 135–140Google Scholar
  44. Timbrell JA, Seabra V, Waterfield CJ (1995) The in vivo and in vitro protective properties of taurine. Gen Pharmac 26: 453–462Google Scholar
  45. Trimble KC, Molloy AM, Scott JM, Weir DG (1993) The effect of ethanol on one-carbon metabolism: increased methionine catabolism and lipotrope methyl-group wastage. Hepatology 18: 984–989Google Scholar
  46. Tsuboi N, Yoshida H, Shibamura K, Hikita M, Tomonari H, Kuriyama S, Sakai O (1997) Acute renal failure after binge drinking of alcohol and nonsteroidal anti-inflammatory drug ingestion. Intern Med 36: 102–106Google Scholar
  47. Vendemiale G, Lieber CS (1984) Acute and chronic effects of ethanol on biliary secretion of bilirubin and bile acids. Subst Alcohol Actions Misuse 5: 307–317Google Scholar
  48. Vessey DA (1978) The biochemical basis for the conjugation of bile acids with either glycine or taurine. Biochem J 174: 621–626Google Scholar
  49. Watanabe A, Hobara N, Nagashima H (1985) Lowering of liver acetaldehyde but not ethanol concentrations by pretreatment with taurine in ethanol-loaded rats. Experientia 41: 1421–1422Google Scholar
  50. Waterfield CJ (1994) Determination of taurine in biological samples and isolated hepatocytes by high performance liquid chromatography with fluorimetric detection. J Chromatography 657: 37–45Google Scholar
  51. Waterfield CJ, Turton JA, Scales MDC, Timbrell JA (1993a) Reduction of liver taurine in rats by β-alanine treatment increases carbon tetrachloride toxicity. Toxicology 77: 7–20Google Scholar
  52. Waterfield CJ, Turton JA, Scales MDC, Timbrell JA (1993b) Investigations into the effects of various hepatotoxin compounds on urinary and liver taurine levels in rats. Arch Toxicol 67: 244–254Google Scholar
  53. Waterfield CJ, Asker DA, Timbrell JA (1996) Does urinary taurine reflect changes in protein metabolism? A study with cycloheximide in rats. Biomarkers 1: 107–114Google Scholar
  54. Yan CC, Bravo E, Cantafora A (1993) Effect of taurine levels on liver lipid metabolism: an in vivo study in the rat. Proc Soc Exp Biol Med 202: 88–96Google Scholar

Copyright information

© Springer-Verlag 1998

Authors and Affiliations

  • M. D. J. Kerai
    • 1
  • Catherine J. Waterfield
    • 3
  • S. H. Kenyon
    • 2
  • D. S. Asker
    • 3
  • J. A. Timbrell
    • 3
  1. 1.Centre for Toxicology, Department of PharmacologyThe School of Pharmacy, University of LondonUnited Kingdom
  2. 2.Department of Pharmaceutical and Biological ChemistryThe School of Pharmacy, University of LondonUnited Kingdom
  3. 3.Department of PharmacyKing's College LondonLondonUnited Kingdom

Personalised recommendations