Lipids

, Volume 33, Issue 1, pp 87–91 | Cite as

Penetration and distribution of α-tocopherol, α- or γ-tocotrienols applied individually onto murine skin

  • Maret G. Traber
  • Michalis Rallis
  • Maurizio Podda
  • Christine Weber
  • Howard I. Maibach
  • Lester Packer
Article

Abstract

To evaluate skin penetration of various vitamin E homologs, a 5% solution of either α-tocopherol, α-tocotrienol, or γ-tocotrienol in polyethylene glycol was topically applied to SKH-1 hairless mice. After 0.5, 1, 2, or 4 h (n=four per time point and four per vitamin E homolog), the skin was washed, the animals killed, the skin rapidlly removed, frozen on dry ice, and a biopsy taken and sectioned: stratum corneum (two uppermost, 5-μm sections—SC1 and SC2), epidermis (next two 10μm sections—E1 and E2), papillary dermis (next 100μ, PD), dermis (next 400 μm, D), and subcutaneous fat (next 100 μm, SF). SC1 contained the highest vitamin E concentrations per μ thickness. To compare the distribution of the various vitamin E forms into the skin layers, the percentage of each form was expressed per its respective total. Most surprising was that the largest fraction of skin vitamin E following topical application was found in the deeper subcutaneous layers—the lowest layers, PD (40±15%) and D (36±15%), contained the major portion of the applied vitamin E forms. Although PD only represents about 16% of the total skin thickness, it contains sebaceous glands—lipid secretory organs, and, thus, may account for the vitamin E affinity for this layer. Hence, applied vitamin E penetrates rapidly through the skin, but the highest concentrations are found in the uppermost 5 microns.

Abbreviations

D

dermis

E

epidermis

MDA

malondialdehyde

PD

papillary dermis

SC

stratum corneum

SF

subcutaneous fat

TRF

tocotrienolrich fraction

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Shindo, Y., Witt, E., Han, D., Epstein, W., and Packer, L. (1994) Enzymic and Non Enzymic Antioxidants in Epidermis and Dermis of Human Skin, J. Invest. Dermatol. 102, 122–124.PubMedCrossRefGoogle Scholar
  2. 2.
    Shindo, Y., Witt, E., Han, D., and Packer, L. (1994) Dose-Response Effects of Acute Ultraviolet Irradiation on Antioxidants and Molecular Markers of Oxidation in Murine Epidermis and Dermis, J. Invest. Dermatol. 102, 470–475.PubMedCrossRefGoogle Scholar
  3. 3.
    Shindo, Y., Witt, E., Han, D., Tzeng, B., Aziz, T., Nguyen, L., and Packer, L. (1994) Recovery of Antioxidants and Reduction in Lipid Hydroperoxides in Murine Epidermis and Dermis After Acute Ultraviolet Radiation Exposure, Photoderm. Photoimmunol. Photomed. 10, 183–191.Google Scholar
  4. 4.
    Fuchs, J., Mehlhorn, R.J., and Packer, L. (1989) Free Radical Reduction Mechanisms in Mouse Epidermis Skin Homogenates, J. Invest. Dermatol. 93, 633–640.PubMedCrossRefGoogle Scholar
  5. 5.
    Fuchs, J., Huflejt, M.E., Rothfuss, L.M., Wilson, D.S., Carcamo, G., and Packer, L. (1989) Impairment Of Enzymic and Nonenzymic Antioxidants in Skin By UVb Irradiation, J. Invest. Dermatol. 93, 769–773.PubMedCrossRefGoogle Scholar
  6. 6.
    Traber, M.G. (1994) Determinants of Plasma Vitamin E Concentrations, Free Radical Biol. Med. 16, 229–239.CrossRefGoogle Scholar
  7. 7.
    Burton, G.W., Joyce, A., and Ingold, K.U. (1982) First Proof That Vitamin E Is Major Lipid-Soluble, Chain-Breaking Antioxidant in Human Blood Plasma, Lancet 8292 Ii, 327.CrossRefGoogle Scholar
  8. 8.
    Burton, G.W., Joyce, A., and Ingold, K.U. (1983) Is Vitamin E the Only Lipid-Soluble, Chain-Breaking Antioxidant in Human Blood Plasma and Erythrocyte Membranes? Arch. Biochem. Biophys. 221, 281–290.PubMedCrossRefGoogle Scholar
  9. 9.
    Kagan, V.E., Serbinova, E.A., Forte, T., Scita, G., and Packer, L. (1992) Recycling of Vitamin E in Human Low Density Lipoproteins, J. Lipid Res. 33, 385–397.PubMedGoogle Scholar
  10. 10.
    Esterbauer, H., Gebicki, J., Puhl, H., and Jurgens, G. (1992) The Role of Lipid Peroxidation and Antioxidants in Oxidative Modification of L.D., Free Radical Biol. Med. 13, 341–390.CrossRefGoogle Scholar
  11. 11.
    Behrens, W.A., and Madere, R. (1987) Mechanisms of Absorption, Transport and Tissue Uptake of RRR-α-Tocopherol and d-γ-Tocopherol in the White Rat, J. Nutr. 117, 1562–1569.PubMedGoogle Scholar
  12. 12.
    Handelman, G.J., Epstein, W.L., Peerson, J., Spiegelman, D., and Machlin, L.J. (1994) Human Adipose α-Tocopherol and γ-Tocopherol Kinetics During and After 1 Y of a Tocopherol Supplementation, Am. J. Clin. Nutr. 59, 1025–1032.PubMedGoogle Scholar
  13. 13.
    Peake, I.R., and Bieri, J.G. (1977) α-and γ-Tocopherols in the Rat: In Vitro And In Vivo Tissue Uptake and Metabolism, J. Nutr. 101, 1615–1622.Google Scholar
  14. 14.
    Hayes, K.C., Pronczuk, A., and Liang, J.S. (1993) Differences in the Plasma Transport and Tissue Concentrations of Tocopherols and Tocotrienols: Observations in Humans and Hamsters. Proc. Soc. Exp. Biol. Med. 202, 353–359.PubMedGoogle Scholar
  15. 15.
    Podda, M., Weber, C., Traber, M.G., and Packer, L. (1996) Simultaneous Determination of Tissue Tocopherols, Tocotrienols, Ubiquinols and Ubiquinones, J. Lipid Res. 37, 893–901.PubMedGoogle Scholar
  16. 16.
    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 Radical Biol. Med. 10, 263–275.CrossRefGoogle Scholar
  17. 17.
    Weber, C., Podda, M., Rallis, M., Traber, M.G., and Packer, L. (1997) Efficacy of Topical Application of Tocopherols and Tocotrienols in Protection of Murine Skin from Oxidative Damage Induced by UV-Irradiation, Free Radical Biol. Med. 22, 761–769.CrossRefGoogle Scholar
  18. 18.
    Thiele, J.J., Traber, M.G., Podda, M., Tsang, K., Cross, C., and Packer, L. (1997) Ozone Depletes Tocopherols and Tocotrienols Topically Applied to Murine Skin, FEBS Lett. 167, 170.Google Scholar
  19. 19.
    Thiele, J.J., Traber, M.G., Tsang, K., Cross, C., and Packer, L. (1997) In Vivo Exposure to Ozone Depletes Vitamins C and E and Induces Lipid Peroxidation in the Upper Epidermis of Murine Skin, Free Radical Biol. Med. 23, 385–391.CrossRefGoogle Scholar
  20. 20.
    Thiele, J.J., Traber, M.G., Tsang, K., Polefka, T., Cross, C., and Packer, L. (1997) Ozone-Exposure Causes Antioxidant Depletion and Lipid Peroxidation in Murine Stratum Corneum, J. Invest. Dermatol. 108, 753–757.PubMedCrossRefGoogle Scholar
  21. 21.
    Dupuis, D., Rougier, A., Roguet, R., Lotte, C., and Kalopissis, G. (1984) In Vivo Relationship Between Horny Layer Reservoir Effect and Percutaneous Absorption in Human and Rat J. Invest. Dermatol. 82, 353–356.PubMedCrossRefGoogle Scholar
  22. 22.
    Abrams, K., Harvell, J., Shriner, D., Wertz, P., Maibach, H., Maibach, H., and Rehfeld, S. (1993) Effect of Organic Solvents on In Vitro Human Skin Water Barrier Function, J. Invest. Dermatol. 101, 609–613.PubMedCrossRefGoogle Scholar
  23. 23.
    Schaefer, H., and Stüttgen, G. (1976) Absolute Concentrations of an Antimycotic Agent, Econazole, in the Human Skin After Local Application, Arzneimittel-Forsch 26, 432–435.Google Scholar
  24. 24.
    Podda, M., Rallis, M., Traber, M.G., Packer, L., and Maibach, H.I. (1996) Kinetic Study of Cutaneous and Subcutaneous Distribution Following Topical Application Of [7,8 14C]Rac-α-Lipoic Acid onto Hairless Mice, Biochem. Pharmacol. 52, 627–633.PubMedCrossRefGoogle Scholar
  25. 25.
    Burton, G.W., Webb, A., and Ingold, K.U. (1985) A Mild, Rapid, and Efficient Method of Lipid Extraction for Use in Determining Vitamin E/Lipid Ratios, Lipids 20, 29–39.PubMedGoogle Scholar
  26. 26.
    Lang, J.K., Gohil, K., and Packer, L. (1986) Simultaneous Determination of Tocopherols, Ubiquinols, and Ubiquinones in Blood, Plasma, Tissue Homogenates, and Subcellular Fractions, Anal Biochem 157, 106–116.PubMedCrossRefGoogle Scholar
  27. 27.
    Trivedi, J.S., Krill, S.L., and Fort, J.J. (1995) Vitamin E as a Human Skin Penetration Enhancer, Eur. J. Pharm. Sci. 3, 241–243.CrossRefGoogle Scholar
  28. 28.
    Kagan, V.E., Serbinova, E.A., Bakalova, R.A., Stoytchev, T.S., Erin, A.N., Prilipko, L.L., and Evstigneeva, R.P. (1990) Mechanisms of Stabilization of Biomembranes by α Tocopherol. The Role of the Hydrocarbon Chain in the Inhibition of Lipid Peroxidation, Biochem Pharmacol. 40, 2403–2413.PubMedCrossRefGoogle Scholar
  29. 29.
    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 Radical Biol. Med. 10, 263–275.CrossRefGoogle Scholar
  30. 30.
    Serbinova, E.A., Tsuchiya, M., Goth, S., Kagan, V.E., and Packer, L. (1993) Antioxidant Action of α-Tocopherol and α-Tocotrienol in Membranes, in Vitamin E In Health And Disease, (Packer, L., and Fuchs, J., eds.) pp. 235–243, Marcel Dekker, Inc., New York.Google Scholar

Copyright information

© AOCS Press 1998

Authors and Affiliations

  • Maret G. Traber
    • 1
  • Michalis Rallis
    • 1
  • Maurizio Podda
    • 1
  • Christine Weber
    • 1
  • Howard I. Maibach
    • 1
  • Lester Packer
    • 1
  1. 1.Department of Molecular and Cell BiologyUniversity of CaliforniaBerkeley
  2. 2.Division of Pharmaceutical TechnologyUniversity of Athens, School of PharmacyAthensGreece
  3. 3.Zentrum der DermatologieKlinikum der J.W. Goethe UniversitätFrankfurt am MainGermany
  4. 4.Department of Biochemistry and NutritionThe Technical University of DenmarkLyngbyDenmark
  5. 5.University of California San Francisco, Surge 110San Francisco

Personalised recommendations