Advertisement

Effect of lecithin in the treatment of ethanol mediated free radical induced hepatotoxicity

  • Subir Kumar Das
  • D. M. Vasudevan
Article

Abstract

Alcoholic liver disease (ALD) develops as a consequence of priming and sensitizing mechanisms rendered by cross-interactions of primary mechanistic factors and secondary risk factors. Liver damage due to consumption of alcohol may be caused by oxygen radicals such as superoxide and hydroxyl radicals, generated during the metabolism of ethanol by the microsomal oxidizing system. Lecithin, an important class of phospholipids contains choline, which is considered as lipotropic factor. The effects of this lecithin as a hepatoprotective drug on body weight and antioxidant status of ethanol-exposed rats were studied. The results were compared with the effects of tocopheryl acetate. From the present study, it can be concluded that ethanol-induced stress can be partly prevented by tocopheryl acetate, and showed best result. Abstination from alcohol also involved for little hepatic regeneration. Supplementation of lecithin showed better effect compared to abstination from alcohol on reversing the effect of ethanol induced liver damage in the present study. Moreover, preventive measures were found to be better than curative treatment. Antioxidants are likely to provide beneficial effects on hepatocyes via desensitization against oxidant stress while inhibiting primary mechanism for expression of proinflammatory and cytotoxic mediators. However, abstinence from alcohol, proper nutrition, and supplementation of antioxidants, vitamins and hepatoprotective drugs are some of the therapeutic options.

Key Words

S-Adenosyl methionine Lecithin Tocopherol Oxidative stress Glutathione 

References

  1. 1.
    Tsukamoto, H. and Lu, S. C. (2001). Current concepts in the pathogenesis of alcoholic liver injury. FASEB J. 15, 1335–1349.PubMedCrossRefGoogle Scholar
  2. 2.
    Finkelstein, J.D. (1990). Methionine metabolism in mammals. J. Nutr. Biochem. 1, 228–237.PubMedCrossRefGoogle Scholar
  3. 3.
    Mato, J.M., Alvarez, L., Corrales, F. and Pajares, M.A. (1994). S-adenosylmethionine and the liver. In: The liver biology and Pathology. Eds., Arias, I.M., Boyer, J.L., Fausto, N., Jakoby, W.B., Schachter, D.A. and Shafritz, D.A. Raven Press, New York; pp. 461–470.Google Scholar
  4. 4.
    Mato, J.M., Alvarez, L., Oritz, P. and Pajares, M.A. (1997). S-adenosylmethionine synthesis: molecular mechanisms and clinical implications. Pharmacol. Ther. 73, 265–280.PubMedCrossRefGoogle Scholar
  5. 5.
    Hoffman, D.R., Marion, D.W., Cornatzer, W.E. and Duerre, J.A. (1980). S-adenosylmethionine and S-adenosylhomocysteine metabolism in isolated rat liver. Effects of L-methionine, L-homocysteine, and adenosine. J. Biol. Chem. 255, 10822–10827.PubMedGoogle Scholar
  6. 6.
    Lu, S.C. (1998). Regulation of hepatic glutathione synthesis. Semin. Liv. Dis. 18, 331–343.CrossRefGoogle Scholar
  7. 7.
    Lieber, C.S., Casini, A., DeCarli, L.M., Kim, C.I., Lowe, N., Saski, R. and Leo, M.A. (1990). S-adenosyl-L-methionine attenuates alcohol-induced liver injury in the baboon. Hepatol. 11, 165–172.CrossRefGoogle Scholar
  8. 8.
    Lieber, C.S., Robins, S.J. and Leo, M.A. (1994). Hepatic phosphaidylethanolamine methyl transferase activity is decreased by ethanol and increased by phosphtidylcholine. Alc. Clin. Exp. Res. 18, 592–595.CrossRefGoogle Scholar
  9. 9.
    Package of Practices Recommendation (2001). Veterinary & Animal Husbandary Department, Kerala Agriculture University, Mannuthy, Thrissur.Google Scholar
  10. 10.
    Lowry, O.H., Rosenbourgh, N.J., Farr, A.L. and Randall, R.J. (1951). Protein measurement with folin phenol reagent. J. Biol. Chem. 193, 265–275.PubMedGoogle Scholar
  11. 11.
    Roe, J.H. and Kuether, C.A. (1943). The determination of ascorbic acid in whole blood and urine through the 2,4-dinitrophenyl hydrazine derivative of dehydro ascorbic acid. J. Biol. Chem. 147, 399–401.Google Scholar
  12. 12.
    Sinnhuber, R.O., Yu, T.C. and Yu, T.C. (1958). Characterization of the red pigment formed in the thiobarbituric acid determination of oxidative rancidity. Food Res. 23, 626–630.Google Scholar
  13. 13.
    Ellman, G.L. (1959). The sulphydryl groups. Arch. Biochem. Biophys. 32, 70–77.CrossRefGoogle Scholar
  14. 14.
    Beers, R.F. and Sizer, I.W. (1952). A spectrophotometric method for measuring the breakdown of hydrogen peroxides by catalase. J. Biol. Chem. 195, 133–140.PubMedGoogle Scholar
  15. 15.
    Nelson, D.P. and Kiesow, L.A. (1972). Enthalpy of decomposition of hydrogen peroxide by catalase at 25°C (with molar extinction coefficients of H2O2 solutions in the UV. Anal. Biochem. 49, 474–478.PubMedCrossRefGoogle Scholar
  16. 16.
    Goldberg, M.D. and Spooner, J.R. (1983). Glutathione reductase. In: Methods Enzyme Analysis. Eds. Bergmayer, H.U., Bergmayer J. and Grabi M. Academic Press, Inc., Florida; Vol. III, 3rd edn. pp. 258–265.Google Scholar
  17. 17.
    Habig, W.H., Pabst, M.J. and Jakoby, W.B. (1974). Glutathione S-transferase, the first enzymatic step in mercapturic acid formation. J. Biol. Chem. 249, 7130–7139.PubMedGoogle Scholar
  18. 18.
    Paglia, D.E. and Valentione, W.N. (1967). Studies on the quantitative and qualitative characterisation of erythrocyte glutathione peroxides. J. Lab. Clin. Med. 70, 158–159.PubMedGoogle Scholar
  19. 19.
    Marklund, S. and Marklund, G. (1974). Involvement of superoxide radical in the auto oxidation pyrogallol and a convenient assay for superoxide dismutase. Eur. J. Biochem. 47, 469–474.PubMedCrossRefGoogle Scholar
  20. 20.
    Das, S.K. and Vasudevan, D.M. (2005). Effect of ethanol on liver antioxidant defense systems: a dose dependent study. Ind. J. Clin. Biochem. 20 (1), 79–83.Google Scholar
  21. 21.
    McClain, C., Hill, D., Schmidt, J. and Diehl, A.M. (2001). Cytokines and alcoholic liver disease. Semin. Liv. Dis. 13, 170–182.Google Scholar
  22. 22.
    Mari, M., Wu, D., Nieto, N. and Cederbaum, A.I. (2001). CYP2E1-dependent toxicity and upregulation of antioxidant genes. J. Biomed. Sci. 8 (1), 52–55.PubMedCrossRefGoogle Scholar
  23. 23.
    Campos, R., Garrido, A., Guerra, R. and Valenzuela, A. (1989). Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver. Planta. Med. 55, 417–419.PubMedCrossRefGoogle Scholar
  24. 24.
    Valenzuela, A., Lagos, C., Schimdt, K. and Videla, K. (1985). Silymarin protection against hepatic lipid peroxidation induced by acute ethanol intoxication in the rat. Biochem. Pharmacol. 3, 2209–2212.CrossRefGoogle Scholar
  25. 25.
    Dinu, V. and Zamfir, O. (1991). Oxidative stress in ethanol intoxicated rats. Rev. Roum. Physiol. 28 (1–2), 63–67.PubMedGoogle Scholar
  26. 26.
    Chandra, R., Aneja, R., Rewal, C., Konduri, R., Dass, S.K. and Agarwal, S. (2000). An opium alkaloid-Papaverine ameliorates ethanol-induced hepatotoxicity: diminution of oxidative stress. Ind. J. Clin. Biochem. 15 (2), 155–160.CrossRefGoogle Scholar
  27. 27.
    Aniya, Y. and Daido, A. (1994). Activation of microsomal glutathione S-transferase in tert-butyl hydroperoxide-induced oxidative stress of isolated rat liver. Jpn. J. Pharmacol. 66 (1), 123–130PubMedCrossRefGoogle Scholar
  28. 28.
    Buettner, G.R. (1993). The pecking order of free radicals and antioxidants: lipid peroxidation, alpha tocopherol and ascorbate. Arch. Biochem. Biophys. 300, 535–543.PubMedCrossRefGoogle Scholar
  29. 29.
    Maellaro, E., Casini, A.F., DelBello, B. and Comporti. (1990). Lipid peroxidation and antioxidant systems in the liver injury produced by glutathione depleting agents. Biochem. Pharmacol. 39 (10), 1513–1521.PubMedCrossRefGoogle Scholar
  30. 30.
    Lieber, C.S., Leo, M.A., Mak, K.M., DeCarli, L.M. and Sato, S. (1985). Choline fails to prevent liver fibrosis in ethanol-fed baboons but causes toxicity. Hepatol. 5 (4), 561–572.CrossRefGoogle Scholar
  31. 31.
    Lieber, C.S., DeCarli, L.M., Mak, K.M., Kim, C.I. and Leo, M.A. (1990). Attenuation of alcohol-induced hepatic fibrosis by polyunsaturated lecithin. Hepatol. 12 (6), 1390–1398.CrossRefGoogle Scholar

Copyright information

© Association of Clinical Biochemists of India 2006

Authors and Affiliations

  1. 1.Department of BiochemistryAmrita Institute of Medical SciencesCochinIndia

Personalised recommendations