The Skin and Its Antioxidant Defense System

While the skin provides a protective barrier over the body surface, it is continuously exposed to various injuries. 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. Free radicals are the culprits, while the antioxidants in the body and in cosmeceutical preparations are both preventative and reparative of ultraviolet radiation induced cutaneous damage.

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. Glutathione, in its reduced form, protects cells against oxidative stress. Glutathione works with the enzyme glutathione peroxidase to break down hydrogen peroxide and lipid hydroperoxides. Glutathione peroxidase uses selenium as a co-factor to exert its biological functions and other selenium compounds work together with glutathione to scavenge oxygen centered radicals.

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-glutathione peroxidase cascade. Glutathione is vital in maintaining the ascorbates of vitamin C and the tocopherols of vitamin E in their reduced form. Thus, the most abundant tissue thiol, glutathione, acts synergistically with the other endogenous antioxidants to scavenge free radicals from biochemical reactions and from effects of therapeutic and ultraviolet radiation and other environmental pollutants.

Preparations incorporating the glutathione antioxidant cycle can repair radiation damaged skin and help prevent photoaging and with the addition of sunscreens, such preparations may enhance prevention of sunburn. Since the glutathione complex also 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. Finally, cosmetic and dermatologic compositions which are used as adjuncts in management of signs and symptoms of various desquamating disorders that are also associated with local inflammatory conditions may be supplemented with the glutathione antioxidant cycle to ameliorate these cutaneous symptoms.

Also See:

» The Aging Process
» Clinical Entities with Low Levels of Glutathione

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