Journal of Physiology and Biochemistry

, Volume 65, Issue 3, pp 225–233 | Cite as

Comparison of vitamin E, L-carnitine and melatonin in ameliorating carbon tetrachloride and diabetes induced hepatic oxidative stress

  • M. E. Shaker
  • M. E. Houssen
  • E. M. Abo-Hashem
  • T. M. Ibrahim


This study aimed to investigate whether treatments with vitamin E, L-carnitine and melatonin can protect against CCl4 and diabetes-induced hepatic oxidative stress. Hepatic oxidative stress was performed in rats through 50% v/v carbon tetrachloride (CCl4) (1 ml/kg/3days, i.p.), and through diabetes mellitus induced by streptozotocin (STZ) (40 mg/kg, i.p.). Vitamin E (100 mg/kg/day, i.p), L-carnitine (300 mg/kg/day, i.p.) and melatonin (10 mg/kg/day, i.p.) were injected for a period of 6 weeks. Thereafter, changes in serum glucose level, liver function tests, hepatic malondialdehyde (MDA) content, hepatic reduced glutathione (GSH) content, hepatic superoxide dismutase (SOD) activity, and serum total antioxidant capacity (TAC) level were evaluated. In CCl4-induced liver fibrosis, the efficacy order was melatonin > L-carnitine > vitamin E, while in STZ-induced diabetes, the efficacy order was vitamin E ≥ melatonin > L-carnitine. In conclusion, these data indicate that low dose of melatonin is more effective than high doses of vitamin E and L-carnitine in reducing hepatic oxidative stress induced by CCl4 and diabetes. Moreover, the potent effect of vitamin E in ameliorating diabetes can be linked not only to the antioxidant actions, but also to the superior effect in reducing diabetes-induced hyperglycaemia. Meanwhile, potency of L-carnitine was nearly the same in CCl4 and diabetes-induced liver damage.

Key words

Vitamin E L-carnitine Melatonin Carbon tetrachloride Diabetes 


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  1. 1.
    Belfield, A., Goldberg, D.M. (1971): Revised assay for serum phenyl phosphatase activity using 4-amino-antipyrine.Enzyme,12, 561–573.PubMedGoogle Scholar
  2. 2.
    Beutler, E., Duron, O., Kelly, B.M. (1963): Improved method for the determination of blood glutathione.J Lab Clin Med,61, 882–888.PubMedGoogle Scholar
  3. 3.
    Boll, M., Weber, L.W., Becker, E., Stampfl, A. (2001): Mechanism of carbon tetrachloride-induced hepatotoxicity. Hepatocellular damage by reactive carbon tetrachloride metabolites.Z Naturforsch,56, 649–659.Google Scholar
  4. 4.
    Brigelius-Flohé, R., Traber, M.G. (1999): Vitamin E: function and metabolism.FASEB J,13, 1145–1155.PubMedGoogle Scholar
  5. 5.
    Broderick T.L., Quinney, H.A., Lopaschuk, G.D. (1995): L-carnitine increases glucose metabolism and mechanical function following ischaemia in diabetic rat heart.Cardiovasc Res,29, 373–378.PubMedGoogle Scholar
  6. 6.
    Capaldo, B., Napoli, R., Di Bonito, P., Albano, G., Saccà, L. (1991): Carnitine improves peripheral glucose disposal in non-insulin-dependent diabetic patients.Diabetes Res Clin Pract,14, 191–195.CrossRefPubMedGoogle Scholar
  7. 7.
    Chawla, R.K., Lewis, F.W., Kutner, M.H., Bate, D.M., Roy, R.G.B., Rudman, D. (1984): Plasma cysteine, cystine, and glutathione in cirrhosis.Gastroenterol,87: 770–775.Google Scholar
  8. 8.
    Demirdag, K., Bahcecioglu, I.H., Ozercan, I.H., Ozden, M., Yilmaz, S., Kalkan, A. (2004): Role of L-carnitine in the prevention of acute liver damage induced by carbon tetrachloride in rats.J Gastroenterol Hepatol,19, 333–338.CrossRefPubMedGoogle Scholar
  9. 9.
    Ferrari, R., Merli, E., Cicchitelli, G., Mele, D., Fucili, A., Ceconi, C. (2004): Therapeutic effects of L-carnitine and propionyl-L-carnitine on cardiovascular diseases: a review.Ann NY Acad Sci,1033, 79–91.CrossRefPubMedGoogle Scholar
  10. 10.
    Gornall, A.G., Bardawill, C.J., David, M.M. (1949): Determination of serum proteins by means of the biuret reaction.J Biol Chem,177, 751–766.PubMedGoogle Scholar
  11. 11.
    Gulcin, I. (2006): Antioxidant and antiradical activities of L-carnitine.Life Sci,78, 803–811.CrossRefPubMedGoogle Scholar
  12. 12.
    Harris, E.H. (2005): Elevated Liver Function Tests in Type 2 Diabetes.Clinical Diabetes,23, 115–119.CrossRefGoogle Scholar
  13. 13.
    Hunt, J.V., Smith, C.C., Wolff, S.P. (1990): Autoxidative glycosylation and possible involvement of peroxides and free radicals in LDL modification by glucose.Diabetes,39, 1420–1424.CrossRefPubMedGoogle Scholar
  14. 14.
    Jain, S.K., McVie, R., Smith, T. (2000): Vitamin E supplementation restores gluthatione and malondialdehyde to normal concentrations in erythrocytes of type 1 diabetic children.Diabetes Care,23, 1389–1394.CrossRefPubMedGoogle Scholar
  15. 15.
    Juránek, I., Bezek, S. (2005): Controversy of free radical hypothesis: reactive oxygen species — cause or consequence of tissue injury?Gen Physiol Biophys,24, 263–278.PubMedGoogle Scholar
  16. 16.
    Koracevic, D., Koracevic, G., Djordjevic, V., Andrejevic, S., Cosic, V. (2001): Method for the measurement of antioxidant activity in human fluids.J Clin Pathol,54, 356–361.CrossRefPubMedGoogle Scholar
  17. 17.
    Lee, T.Y., Mai, L.M., Wang, G.J., Chiu, J.H., Lin, Y.L., Lin, H.C. (2003): Protective mechanism of Salvia miltiorrhiza on carbon tetrachloride-induced acute hepatotoxicity in rats.J Pharmacol Sci,91, 202–210.CrossRefPubMedGoogle Scholar
  18. 18.
    Marklund, S., Marklund, G. (1974): Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase.Eur J Biochem,47, 469–474.CrossRefPubMedGoogle Scholar
  19. 19.
    Marshall, K.A., Reiter, R.J., Poeggeler, B., Aruoma, O.I., Halliwell, B. (1996): Evaluation of the antioxidant activity of melatonin in vitro.Free Radic Biol Med,21, 307–315.CrossRefPubMedGoogle Scholar
  20. 20.
    McLennan, S.V., Heffernan, S., Wright, L., Rae, C., Fisher, E., Yue, D.K., Turtle, J.R. (1991): Changes in hepatic glutathione metabolism in diabetes.Diabetes,40, 344–348.CrossRefPubMedGoogle Scholar
  21. 21.
    Ohkawa, H., Ohishi, N., Yagi, K. (1979): Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.Anal Biochem,95, 351–358.CrossRefPubMedGoogle Scholar
  22. 22.
    Oliveira, H.R., Curi, R., Carpinelli, A.R. (1999): Glucose induces an acute increase of superoxide dismutase activity in incubated rat pancreatic islets.Am J Physiol,276, 507–510.Google Scholar
  23. 23.
    Paolisso, G., Di Maro, G., Galzerano, D., Cacciapuoti, F., Varricchio, G., Varricchio, M., D’Onofrio, F. (1994): Pharmacological doses of vitamin E and insulin action in elderly subjects.Am J Clin Nutr,59, 1291–1296.PubMedGoogle Scholar
  24. 24.
    Pitsavos, C., Panagiotakos, D.B., Tzima, N., Chrysohoou, C., Economou, M., Zampelas, A., Stefanadis, C. (2005): Adherence to the Mediterranean diet is associated with total antioxidant capacity in healthy adults: the ATTICA study.Am J Clin Nutr,82, 694–699.PubMedGoogle Scholar
  25. 25.
    Rajasekar, P., Kaviarasan, S., Anuradha, C.V. (2005): L-carnitine administration prevents oxidative stress in high fructose-fed insulin resistant rats.Diabetol Croat,34: 21–28.Google Scholar
  26. 26.
    Reiter, R.J., Tan, D.X., Mayo, J.C., Sainz, R.M., Leon, J., Czarnocki, Z. (2003): Melatonin as an antioxidant: biochemical mechanisms and pathophysiological implications in humans.Acta Biochim Pol,50, 1129–1146.PubMedGoogle Scholar
  27. 27.
    Reitman, S., Frankel, S. (1957): A colorimetric method for the determination of serum glutamic oxaloacetic and glutamic pyruvic transaminases.Am J Clin Pathol,28, 56–63.PubMedGoogle Scholar
  28. 28.
    Rolo, A.P., Palmeira, C.M. (2006): Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress.Toxicol Appl Pharmacol,212, 167–178.CrossRefPubMedGoogle Scholar
  29. 28.
    Schneider, C. (2005): Chemistry and biology of vitamin E.Mol Nutr Food Res,49, 7–30.CrossRefPubMedGoogle Scholar
  30. 30.
    Tan, D.X., Manchester, L.C., Terron, M.P., Flores, L.J., Reiter, R.J. (2007): One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species?J Pineal Res,42, 28–42.CrossRefPubMedGoogle Scholar
  31. 31.
    Trinder, P. (1969): Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor.Ann Clin Biochem,6, 24–28.Google Scholar
  32. 32.
    Urata, Y., Honma, S., Goto, S., Todoroki, S., Ueda, T., Cho, S., Honma, K., Kondo, T. (1999): Melatonin induces gammaglutamylcysteine synthetase mediated by activator protein-1 in human vascular endothelial cells.Free Radic Biol Med,27, 838–847.CrossRefPubMedGoogle Scholar
  33. 33.
    Vozarova, B., Stefan, N., Lindsay, R.S., Saremi, A., Pratley, R.E., Bogardus, C., Tataranni, P.A. (2002): High alanine aminotransferase is associated with decrease hepatic insulin sensitivity and predicts the development of type 2 diabetes.Diabetes,51, 1189–1195.Google Scholar
  34. 34.
    Wang, H., Wei, W., Wang, N.P., Gui, S.Y., Wu, L., Sun, W.Y., Xu, S.Y. (2005): Melatonin ameliorates carbon tetrachloride-induced hepatic fibrogenesis in rats via inhibition of oxidative stress.Life Sci,77, 1902–1915.CrossRefPubMedGoogle Scholar
  35. 35.
    Weber, L.W., Boll, M., Stampfl, A. (2003): Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model.Cri Rev Toxicol,33, 105–136.CrossRefGoogle Scholar
  36. 36.
    Wefers, H., Sies, H. (1988): The protection by ascorbate and glutathione against microsomal lipid peroxidation is dependent on vitamin E.Eur J Biochem,174, 353–357.CrossRefPubMedGoogle Scholar
  37. 37.
    Wolf, R., Wolf, D., Ruocco, V. (1998): Vitamin E: the radical protector.J Eur Acad Dermatol Venereol,10, 103–117.CrossRefPubMedGoogle Scholar

Copyright information

© Universidad de Navarra 2009

Authors and Affiliations

  • M. E. Shaker
    • 1
  • M. E. Houssen
    • 2
  • E. M. Abo-Hashem
    • 3
  • T. M. Ibrahim
    • 1
  1. 1.Department of Pharmacology and Toxicology, Faculty of PharmacyUniversity of MansouraMansouraEgypt
  2. 2.Department of Biochemistry, Faculty of PharmacyUniversity of Beni SueifBeni SueifEgypt
  3. 3.Department of Clinical Pathology, Faculty of MedicineUniversity of MansouraMansouraEgypt

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