, Volume 40, Issue 6, pp 575–580 | Cite as

Comparative effects of palm vitamin E and α-tocopherol on healing and wound tissue antioxidant enzyme levels in diabetic rats

  • M. Musalmah
  • M. Y. Nizrana
  • A. H. Fairuz
  • A. H. NoorAini
  • A. L. Azian
  • M. T. Gapor
  • W. Z. Wan Ngah


The effect of supplementing 200 mg/kg body weight palm vitamin E (PVE) and 200 mg/kg body weight α-tocopherol (α-loc) on the healing of wounds in streptozotocin-induced diabetic rats was evaluated. The antioxidant potencies of these two preparations of vitamin E were also evaluated by determining the antioxidant enzyme activities, namely, glutathione peroxidase (GPx) and superoxide dismutase (SOD), and malondialdehyde (MDA) levels in the healing of dermal wounds. Healing was evaluated by measuring wound contractions and protein contents in the healing wounds. Cellular redistribution and collagen deposition were assessed morphologically using cross-sections of paraffin-embedded day-10 wounds stained according to the Van Gieson method. GPx and SOD activities as well as MDA levels were determined in homogenates of day-10 dermal wounds. Results showed that PVE had a greater potency to enhance wound repair and induce the increase in free radical-scavenging enzyme activities than α-Toc. Both PVE and α-Toc, however, were potent antioxidants and significantly reduced the lipid peroxidation levels in the wounds as measured by the reduction in MDA levels.



glutathione peroxidase




nitroblue tetrazolium chloride


palm vitamin E


superoxide dismutase




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  1. 1.
    Pennock, J.F., Hemming, F.W., and Kerr, J.D. (1964) A Reassessment of Tocopherol in Chemistry, Biochem. Biophys. Res. Commun. 17, 542–548.PubMedCrossRefGoogle Scholar
  2. 2.
    Serbinova, E., Kagan, V., Han, D., and Packer, L. (1991) Free Radical Recycling and Intramembrane Mobility in the Antioxidant Properties of α-Tocopherol and α-Tocotrienol, Free Radic. Biol. Med. 10, 263–275.PubMedCrossRefGoogle Scholar
  3. 3.
    Suzuki, Y.J., Tsuchiya, M., Wassall, S.R., Choo, Y.M., Govil, G., Kagan, V.E., and Packer, L. (1993) Structural and Dynamic Membrane Properties of α-Tocopherol and α-Tocotrienol: Implication to the Molecular Mechanism of Their Antioxidant Potency, Biochemistry 32, 10692–10699.PubMedCrossRefGoogle Scholar
  4. 4.
    Birt, D.F. (1986) Update on the Effect of Vitamins A, C and E and Selenium on Carcinogenesis, Proc. Soc. Exp. Biol. Med. 138, 311–315.Google Scholar
  5. 5.
    Sen, C.K., Khanna, S., Roy, S., and Packer, L. (2000) Tocotrienol Potently Inhibits Glutamate-Induced pp60c-Src Kinase Activity and Death of HT4 Neuronal Cells, Biol. Chem. 275, 13049–13055.CrossRefGoogle Scholar
  6. 6.
    Suarna, C., Hood, R.L., Dean, R.T., and Stocker, R. (1993) Comparative Antioxidant Activity of Tocotrienols and Other Natural-Lipid Soluble Antioxidants in a Homogenous System, and in Rat and Human Lipoproteins, Biochim. Biophys. Acta 1166, 163–170.PubMedGoogle Scholar
  7. 7.
    Gapor, M.T., and Hashimoto, T. (1983) Effects of Processing on the Content and Composition of Tocopherols and Tocotrienols in Palm Oil, in Palm Oil Product Technology in the Eighties: A Report of the Proceedings of the International Conference on Palm Oil Product Technology in the Eighties (Pushparajah, E., and Rajagurai, M., eds.), pp. 145–156, Incorporated Society of Planters.Google Scholar
  8. 8.
    Hallberg, C.K., Troome, S.D., and Ansari, N.H. (1996) Acceleration of Corneal Wound Healing in Diabetic Rats by Antioxidant Trolox, Res. Commun. Mol. Pathol. Pharmacol. 93, 3–12.PubMedGoogle Scholar
  9. 9.
    Ceriello, A., Falleti, E., Moltz, E., Taboga, C., Tonutti, L., Ezsol, Z., Ganano, F., and Bartolli, E. (1998) Hyperglycaemia-Induced ICAM-1 Increase in Diabetes Mellitus: The Possible Role of Oxidative Stress, Horm. Metab. Res. 30, 146–149.PubMedCrossRefGoogle Scholar
  10. 10.
    Maxwell, S.R., Thomason, H., Sandler, D., LeGuen, C., Baxter, M.A., Thorpe, G.H., Jones, A.F., and Barnett, A.H. (1997) Poor Glycaemic Control Is Associated with Reduced Serum Free Radical Scavenging (antioxidant) Activity in NIDDM, Ann. Clin. Biochem. 34 (pt 6), 638–644.PubMedGoogle Scholar
  11. 11.
    Ringsdorf, W.M., Jr., and Cheraskin, E. (1982) Vitamin C and Human Wound Healing, Oral Surg. Oral Med. Oral Path. 53, 231–236.PubMedCrossRefGoogle Scholar
  12. 12.
    Haws, M., Brown, R.E., Suchy, H., and Roth, A. (1994) Vitamin-A Soaked Gelfoam Sponges and Wound Healing in Steroid-Treated Animals, Ann. Plast. Surg. 194, 42–50.Google Scholar
  13. 13.
    Trevisani, M.F., Ricci, M.A., Tolland, J.T., and Beck, W.C. (1987) Effect of Vitamin A and Zinc on Wound Healing in Steroid-Treated Mice, Curr. Surg. 44, 390–393.PubMedGoogle Scholar
  14. 14.
    Weinzweig, J., Levenson, S.M., Rettura, G., Weinzweig, N., Mendecki, J., Chang, T.H., and Seifter, E. (1990) Supplemental Vitamin A Prevents the Tumor-Induced Defect in Wound Healing, Ann. Surg. 211, 269–276.PubMedGoogle Scholar
  15. 15.
    Seifter, E., Retture, G., Padawer, J., Stratford, F., Kambosos, D., and Levenson, S.M. (1981) Impaired Wound Healing in Streptozotocin Diabetes. Prevention by Supplemental Vitamin A, Ann. Surg. 194, 42–50.PubMedCrossRefGoogle Scholar
  16. 16.
    Martin, A. (1996) The Use of Antioxiodants in Healing, Dermatol. Surg. 22, 156–160.PubMedCrossRefGoogle Scholar
  17. 17.
    Nachbar, F., and Korting, H.C. (1995) The Role of Vitamin E in Normal and Damaged Skin, J. Mol. Med. 73, 7–17.PubMedCrossRefGoogle Scholar
  18. 18.
    Fryer, M.J. (1993) Evidence for the Photoprotective Effects of Vitamin E, Photochem. Photobiol. 58, 304–312.PubMedGoogle Scholar
  19. 19.
    Taren, D.L., Chvapil, M., and Weber, C.M. (1987) Increasing the Breaking Strength of Wounds Exposed to Preoperative Radiation Using Vitamin E Supplementation, Int. J. Vitam. Nutr. Res. 57, 133–137.PubMedGoogle Scholar
  20. 20.
    Altavilla, D., Saitta, A., Cucinotta, D., Galeano, M., Deodato, B., Colonna, M., Torre, V., Russo, G., Sardella, A., Urna, G., et al. (2001) Inhibition of Lipid Peroxidation Restores Impaired Vascular Endothelial Growth Factor Expression and Stimulates Wound Healing and Angiogenesis in the Genetically, Diabetic Mouse, Diabetes 50, 667–674.PubMedGoogle Scholar
  21. 21.
    Galeano, M., Torre, V., Deodato, B., Campo, G.M., Colonna, M., Sturiale, A., Squadrito, F., Cavallari, V., Cucinotta, D., Buemi, M., and Altavilla, D. (2001) Raxofelast, a Hydrophilic Vitamin E-like Antioxidant, Stimulates Wound Healing in Genetically Diabetic Mice, Surgery 129, 467–477.PubMedGoogle Scholar
  22. 22.
    Musalmah, M., Fairuz, A.H., Gapor, M.T., and Wan Ngah, W.Z. (2002) Effect of Vitamin E on Plasma Malondialdehyde, Antioxidant Enzyme Levels and the Rates of Wound Closures During Wound Healing in Normal and Diabetic Rats, Asia Pac. J. Clin. Nutr. 11 (Suppl. 7), S448-S451.PubMedCrossRefGoogle Scholar
  23. 23.
    Baci, S.H., and Sheikh, K.A. (2000) The Wound Healing Properties of Channa striatus-Cetrimide Cream—Wound Contraction and Glycosaminoglycan Measurement, J. Ethnopharmacol. 73, 15–30.CrossRefGoogle Scholar
  24. 24.
    Bradford, M.M. (1976) A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding, Anal. Biochem. 72, 248–254.PubMedCrossRefGoogle Scholar
  25. 25.
    Bancroft, J.D., and Cook, H.C. (1984) Manual of Histological Techniques, Churchill Livingstone, Edinburgh.Google Scholar
  26. 26.
    Paglia, D.E., and Valentine, W.N. (1984) Studies on the Quantitative and Qualitative Characterization of Erythrocyte Glutathione Peroxidase, J. Lab. Clin. Med. 7, 158–169.Google Scholar
  27. 27.
    Beyer, W.F., and Fridovich, I. (1987) Assaying for SOD Activity: Some Large Consequences in Minor Changes in Conditions, Anal. Biochem. 161, 559–566.PubMedCrossRefGoogle Scholar
  28. 28.
    Ledwozyw, A., Michalak, J., Stepien, A., and Kadziolka, A. (1986) The Relationship Between Plasma Triglyceride, Cholesterol, Total Lipids and Lipid Peroxidation Products During Human Atheroclerosis, Clin. Chim. Acta 155, 275–284.PubMedCrossRefGoogle Scholar
  29. 29.
    Chithra, P., Sajthlal, G.B., and Chandrakasan, G. (1998) Influence of Aloe Vera on Collagen Characteristics in Healing Dermal Wounds in Rats, Mol. Cell. Biochem. 181, 71–76.PubMedCrossRefGoogle Scholar
  30. 30.
    Raghow, R. (1994) The Role of Extracellular Matrix Post-inflammatory Wound Healing and Fibrosis, FASEB J. 8, 823–831.PubMedGoogle Scholar
  31. 31.
    Bhartiya, D., Sklarsh, J.W., and Maheshwari, R.K. (1992) Enhanced Wound Healing in Animal Models by Interferon and on Interferon Inducer, J. Cell. Physiol. 150, 312–319.PubMedCrossRefGoogle Scholar
  32. 32.
    Chandrasoma, P., and Taylor, C.R. (1995) Healing and Repair, in Concise Pathology, 2nd edn., pp. 78–88, Appleton & Lange, Norwalk, CT.Google Scholar
  33. 33.
    Traber, M.G., Podda, M., Weber, C., Yan, L.J., and Packer, L. (1997) Diet Derived and Topically Applied Tocotrienols Accumulate in Skin and Protect the Tissue Against UV-Induced Oxidative Stress, Asia Pac. J. Clin. Nutr. 6, 63–67.Google Scholar
  34. 34.
    Kamat, J.P., and Devasagayam, T.P.A. (1995) Tocotrienols from Palm Oil as Potent Inhibitors of Lipid Peroxidation and Protein Oxidation in Rat Brain Mitochondria, Neurosci. Lett. 195, 179–182.PubMedCrossRefGoogle Scholar
  35. 35.
    Lopez-Torres, M., Thiele, J.J., Shindo, Y., Han, D., and Packer, L. (1998) Topical Application of α-Tocopherol Modulates the Antioxidant Network and Diminishes Ultraviolet-Induced Oxidative Damage in Murine Skin, Br. J. Derm. 138, 207–215.CrossRefGoogle Scholar
  36. 36.
    Weber, C., Podda, M., Rallis, M., Thiele, J.J., Traber, M.G., and Packer, L. (1997) Efficacy of Topically Applied Tocopherols and Tocotrienols in Protection of Murine Skin from Oxidative Damage Induced by UV-Irradiation, Free Radic. Biol. Med. 22, 761–769.PubMedCrossRefGoogle Scholar
  37. 37.
    Komiyama, K., Lizuka, K., Yamaoka, M., Watanabe, H., Tsuchiya, H., Umezawa, I. (1989) Studies on the Biological Activity of Tocotrienols, Chem. Pharm. Bull. 37, 1369–1371.PubMedGoogle Scholar
  38. 38.
    Nesaretnam, K., Guthrie, N., Chambers, A.F., and Carroll, K.K. (1995) Effects of Tocotrienols on the Growth of a Human Breast Cancer Line in Culture, Lipids 30, 1139–1143.PubMedGoogle Scholar
  39. 39.
    Nesaretnam, K., Stephen, R., Dils, R., and Darbre, P. (1998) Tocotrienols Inhibit the Growth of Human Breast Cancer Lines Irrespective of Estrogen Receptor Status, Lipids 33, 461–469.PubMedCrossRefGoogle Scholar
  40. 40.
    Qureshi, A.A., Qureshi, N., Wright, J.J.K., Shen, Z., Kramer, G., Gapor, A., and Chong, Y.H. (1991) Lowering of Serum Cholesterol in Hypercholesterolemic Humans by Tocotrienols (palm vitee), Am. J. Clin. Nutr 53, 1021S-1026S.PubMedGoogle Scholar
  41. 41.
    Ong, F.B., Wan Ngah, W.Z., Top, A.G., Khalid, B.A., and Shamaan, N.A. (1994) Vitamin E, Glutathione S-Transferase and α-Glutamyl Transpeptidase Activities in Cultured Hepatocytes of Rats Treated with Carcinogens, Int. J. Biochem. 26, 397–402.PubMedCrossRefGoogle Scholar
  42. 42.
    Vervaart, P., and Knight, K.R. (1996) Oxidative Stress and the Cell, Clin. Biochem. Rev. 17, 3–13.Google Scholar

Copyright information

© AOCS Press 2005

Authors and Affiliations

  • M. Musalmah
    • 1
  • M. Y. Nizrana
    • 1
  • A. H. Fairuz
    • 1
  • A. H. NoorAini
    • 1
  • A. L. Azian
    • 2
  • M. T. Gapor
    • 3
  • W. Z. Wan Ngah
    • 1
  1. 1.Department of Biochemistry, Faculty of MedicineUniversiti Kebangsaan MalaysiaKuala LumpurMalaysia
  2. 2.Department of Anatomy, Faculty of MedicineUniversiti Kebangsaan MalaysiaKuala LumpurMalaysia
  3. 3.Department of ChemistryMalaysian Palm Oil BoardBangiMalaysia

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