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
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.
» Clinical Entities
with Low Levels of Glutathione
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