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The Skin and Its Antioxidant Defense System: The Glutathione (GSH) Cycle

Theodore Hersh, MD, MACG
Professor of Medicine, Emeritus, Emory University
Presented at the Health & Beauty Association, June 1998

While the skin provides a protective barrier over the body surface, it is continuously exposed to various injuries. These insults in inflammatory responses, including the generation of toxic oxygen and other free radical species. The skin has a well developed antioxidant defense system, with L-glutathione (GSH) as the key antioxidant.

Ultraviolet radiation and atmospheric oxygen elicit cutaneous free radical reactions. Acute ultraviolet injury causes the erythema we know as sunburn. Chronic exposure leads to early aging of the skin called photo-aging and increases the risks of developing basal cell and squamous cell carcinomas. Malignant melanomas are more closely associated with intense and intermittent sun exposure particularly during childhood and are related to appearance of melanocytic nevi in the UV exposed surfaces. Protection with sun blockers and clothing is paramount. Free radicals are the culprits, while the antioxidants in the body and in cosmeceutical preparations with all their additional cosmetic properties are both preventative and reparative of ultraviolet radiation induced cutaneous damage. This is the most commonly employed system fitting our seminar's title: Cosmetics as Therapeutics and Vice Versa.

It is hypothesized that when tissues are exposed to radiation, energy is absorbed by water contained within the cells resulting in breakage of the oxygen-hydrogen covalent bonds of the water molecule leaving hydrogen and hydroxyl radicals. The latter radical is very reactive with other biomolecules and is responsible for setting off other free radical chain reactions.

The skin is a highly vascular organ rich in polyunsaturated fatty acids. When exposed to therapeutic and ultraviolet radiation, plus other cutaneous damaging environmental pollutants, including tobacco smoke, a peroxidation reaction of lipids in the skin occurs, releasing reactive oxygen species, hydroperoxides and other free radical species. These reactive oxygen species degrade collagen, depolymerize hyaluronic acid, disrupt cell membranes and cause breaks in DNA resulting in mutations which increase the risk of developing cutaneous neoplasias.

In order to combat the free radicals, the skin, like other organs, has a well developed antioxidant system, including reparative and chain breaking antioxidants. Enzymes include superoxide dismutase and catalase. The thiol tripeptide, L-glutathione, in its reduced form (GSH), protects cells against oxidative stress. Since L-glutathione is itself oxidized in these reactions with free radicals, it must act in combination with other enzyme systems and cellular antioxidant molecules in order to be reduced, so that it may renew its role as a free radical scavenger.

GSH functions co-ordinately with the enzyme glutathione peroxidase also to break down hydrogen peroxide and lipid hydroperoxides. GSH peroxidase uses selenium as a co-factor to exert its biological functions. Also, other selenium compounds together with GSH have been shown to scavenge oxygen centered radicals. Thus, the most abundant tissue thiol, GSH, acts synergistically with the other endogenous antioxidants to scavenge free radicals from biochemical reactions and from efforts of therapeutic and ultraviolet radiation and other environmental pollutants.

The exogenous antioxidants, vitamins C and E, are provided from foodstuffs, vitamin supplements and topical cosmeceuticals. The former, as ascorbates, repair oxidizing radicals directly as chain breaking antioxidants and also stimulate synthesis of collagen. The latter, tocopherols, act also as chain breaking antioxidants in the process of lipid peroxidation. Vitamin C, a water soluble molecule, is located in aqueous phases of cells while vitamin E is in the lipid portion of the cell membranes. However, together they function synergistically in addition to their metabolic role in the glutathione-selenium-GSH peroxidase cascade. GSH is vital in maintaining the ascorbates of vitamin C and the tocopherols of vitamin E in their reduced form so that these may properly function as a defensive cycle as the prime antioxidant system in cells and body fluids.

A partial list of such preparations might include the aforementioned compositions with the GSH antioxidant complex to repair radiation damaged skin and help prevent photoaging. Also, with the addition of sunscreens, the GSH antioxidant preparations may serve to enhance preventative aspects to "sunburn". In addition, as the GSH complex combats free radical species generated by various types of cutaneous injuries such as chemical, radiation and thermal "burns", including post-cosmetic laser surgery, other wound healing agents such as zinc compounds and epidermal cell growth factors may be incorporated in these compositions. Lastly, a number of cosmetics which are used as adjuncts in management of signs and symptoms of various desquamating disorders and these with dry and itchy skin which are also associated with local inflammatory conditions, may be supplemented for therapeutic properties of the GSH antioxidant cycle, plus other agents known to ameliorate these associated cutaneous symptoms.

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