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
Full Text
The Full Text of this article is available as a PDF (99.5 KB).
References
- 1.Tsukamoto H., Lu S. C. Current concepts in the pathogenesis of alcoholic liver injury. FASEB J. 2001;15:1335–1349. doi: 10.1096/fj.00-0650rev. [DOI] [PubMed] [Google Scholar]
- 2.Finkelstein J.D. Methionine metabolism in mammals. J. Nutr. Biochem. 1990;1:228–237. doi: 10.1016/0955-2863(90)90070-2. [DOI] [PubMed] [Google Scholar]
- 3.Mato J.M., Alvarez L., Corrales F., Pajares M.A. S-adenosylmethionine and the liver. In: Arias I.M., Boyer J.L., Fausto N., Jakoby W.B., Schachter D.A., Shafritz D.A., editors. The liver biology and Pathology. New York: Raven Press; 1994. pp. 461–470. [Google Scholar]
- 4.Mato J.M., Alvarez L., Oritz P., Pajares M.A. S-adenosylmethionine synthesis: molecular mechanisms and clinical implications. Pharmacol. Ther. 1997;73:265–280. doi: 10.1016/S0163-7258(96)00197-0. [DOI] [PubMed] [Google Scholar]
- 5.Hoffman D.R., Marion D.W., Cornatzer W.E., Duerre J.A. S-adenosylmethionine and S-adenosylhomocysteine metabolism in isolated rat liver. Effects of L-methionine, L-homocysteine, and adenosine. J. Biol. Chem. 1980;255:10822–10827. [PubMed] [Google Scholar]
- 6.Lu S.C. Regulation of hepatic glutathione synthesis. Semin. Liv. Dis. 1998;18:331–343. doi: 10.1055/s-2007-1007168. [DOI] [PubMed] [Google Scholar]
- 7.Lieber C.S., Casini A., DeCarli L.M., Kim C.I., Lowe N., Saski R., Leo M.A. S-adenosyl-L-methionine attenuates alcohol-induced liver injury in the baboon. Hepatol. 1990;11:165–172. doi: 10.1002/hep.1840110203. [DOI] [PubMed] [Google Scholar]
- 8.Lieber C.S., Robins S.J., Leo M.A. Hepatic phosphaidylethanolamine methyl transferase activity is decreased by ethanol and increased by phosphtidylcholine. Alc. Clin. Exp. Res. 1994;18:592–595. doi: 10.1111/j.1530-0277.1994.tb00915.x. [DOI] [PubMed] [Google Scholar]
- 9.Package of Practices Recommendation (2001). Veterinary & Animal Husbandary Department, Kerala Agriculture University, Mannuthy, Thrissur.
- 10.Lowry O.H., Rosenbourgh N.J., Farr A.L., Randall R.J. Protein measurement with folin phenol reagent. J. Biol. Chem. 1951;193:265–275. [PubMed] [Google Scholar]
- 11.Roe J.H., Kuether C.A. The determination of ascorbic acid in whole blood and urine through the 2,4-dinitrophenyl hydrazine derivative of dehydro ascorbic acid. J. Biol. Chem. 1943;147:399–401. [Google Scholar]
- 12.Sinnhuber R.O., Yu T.C., Yu T.C. Characterization of the red pigment formed in the thiobarbituric acid determination of oxidative rancidity. Food Res. 1958;23:626–630. [Google Scholar]
- 13.Ellman G.L. The sulphydryl groups. Arch. Biochem. Biophys. 1959;32:70–77. doi: 10.1016/0003-9861(59)90090-6. [DOI] [PubMed] [Google Scholar]
- 14.Beers R.F., Sizer I.W. A spectrophotometric method for measuring the breakdown of hydrogen peroxides by catalase. J. Biol. Chem. 1952;195:133–140. [PubMed] [Google Scholar]
- 15.Nelson D.P., Kiesow L.A. Enthalpy of decomposition of hydrogen peroxide by catalase at 25°C (with molar extinction coefficients of H2O2 solutions in the UV. Anal. Biochem. 1972;49:474–478. doi: 10.1016/0003-2697(72)90451-4. [DOI] [PubMed] [Google Scholar]
- 16.Goldberg M.D., Spooner J.R. Glutathione reductase. In: Bergmayer H.U., Bergmayer J., Grabi M., editors. Methods Enzyme Analysis. 3rd edn. Florida: Academic Press, Inc.; 1983. pp. 258–265. [Google Scholar]
- 17.Habig W.H., Pabst M.J., Jakoby W.B. Glutathione S-transferase, the first enzymatic step in mercapturic acid formation. J. Biol. Chem. 1974;249:7130–7139. [PubMed] [Google Scholar]
- 18.Paglia D.E., Valentione W.N. Studies on the quantitative and qualitative characterisation of erythrocyte glutathione peroxides. J. Lab. Clin. Med. 1967;70:158–159. [PubMed] [Google Scholar]
- 19.Marklund S., Marklund G. Involvement of superoxide radical in the auto oxidation pyrogallol and a convenient assay for superoxide dismutase. Eur. J. Biochem. 1974;47:469–474. doi: 10.1111/j.1432-1033.1974.tb03714.x. [DOI] [PubMed] [Google Scholar]
- 20.Das S.K., Vasudevan D.M. Effect of ethanol on liver antioxidant defense systems: a dose dependent study. Ind. J. Clin. Biochem. 2005;20(1):79–83. doi: 10.1007/BF02893047. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.McClain C., Hill D., Schmidt J., Diehl A.M. Cytokines and alcoholic liver disease. Semin. Liv. Dis. 2001;13:170–182. doi: 10.1055/s-2007-1007347. [DOI] [PubMed] [Google Scholar]
- 22.Mari M., Wu D., Nieto N., Cederbaum A.I. CYP2E1-dependent toxicity and upregulation of antioxidant genes. J. Biomed. Sci. 2001;8(1):52–55. doi: 10.1007/BF02255971. [DOI] [PubMed] [Google Scholar]
- 23.Campos R., Garrido A., Guerra R., Valenzuela A. Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver. Planta. Med. 1989;55:417–419. doi: 10.1055/s-2006-962055. [DOI] [PubMed] [Google Scholar]
- 24.Valenzuela A., Lagos C., Schimdt K., Videla K. Silymarin protection against hepatic lipid peroxidation induced by acute ethanol intoxication in the rat. Biochem. Pharmacol. 1985;3:2209–2212. doi: 10.1016/0006-2952(85)90421-6. [DOI] [PubMed] [Google Scholar]
- 25.Dinu V., Zamfir O. Oxidative stress in ethanol intoxicated rats. Rev. Roum. Physiol. 1991;28(1–2):63–67. [PubMed] [Google Scholar]
- 26.Chandra R., Aneja R., Rewal C., Konduri R., Dass S.K., Agarwal S. An opium alkaloid-Papaverine ameliorates ethanol-induced hepatotoxicity: diminution of oxidative stress. Ind. J. Clin. Biochem. 2000;15(2):155–160. doi: 10.1007/BF02883745. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Aniya Y., Daido A. Activation of microsomal glutathione S-transferase in tert-butyl hydroperoxide-induced oxidative stress of isolated rat liver. Jpn. J. Pharmacol. 1994;66(1):123–130. doi: 10.1254/jjp.66.123. [DOI] [PubMed] [Google Scholar]
- 28.Buettner G.R. The pecking order of free radicals and antioxidants: lipid peroxidation, alpha tocopherol and ascorbate. Arch. Biochem. Biophys. 1993;300:535–543. doi: 10.1006/abbi.1993.1074. [DOI] [PubMed] [Google Scholar]
- 29.Maellaro E., Casini A.F., DelBello B., Comporti Lipid peroxidation and antioxidant systems in the liver injury produced by glutathione depleting agents. Biochem. Pharmacol. 1990;39(10):1513–1521. doi: 10.1016/0006-2952(90)90515-M. [DOI] [PubMed] [Google Scholar]
- 30.Lieber C.S., Leo M.A., Mak K.M., DeCarli L.M., Sato S. Choline fails to prevent liver fibrosis in ethanol-fed baboons but causes toxicity. Hepatol. 1985;5(4):561–572. doi: 10.1002/hep.1840050407. [DOI] [PubMed] [Google Scholar]
- 31.Lieber C.S., DeCarli L.M., Mak K.M., Kim C.I., Leo M.A. Attenuation of alcohol-induced hepatic fibrosis by polyunsaturated lecithin. Hepatol. 1990;12(6):1390–1398. doi: 10.1002/hep.1840120621. [DOI] [PubMed] [Google Scholar]