Darlene McCord Antioxidants

The outermost layer of the skin, the stratum corneum, is metabolically active and requires antioxidants and specific nutrients to maintain its integrity and proper function. Topically applied antioxidants reduce free radicals in skin cells and substantially inhibit the biochemical cascades responsible for infected and inflamed skin. There is an expressed concern in the scientific community that oral antioxidants may reduce oxidizing free radicals created by radiotherapy. However, there is significant evidence that exogenous antioxidants produce beneficial effects in numerous cancer cell lines. Multiple animal and human studies have demonstrated an increased effectiveness of cancer therapeutic agents, as well as decreased adverse effects, when given concomitantly with topical antioxidant application.

One of the most effective antioxidants in the terms of free radical scavenging is 3,4-dihydroxyphenyl ethanol or hydroxytyrosol (HT). HT is a simple phenol found predominantly in the aqueous fraction of olive pulp. HT application has been found to prevent both radiation-induced protein damage and radiation-induced oxidative DNA damage. The protective effects provided by HT are relevant to the radiation-induced DNA damage manifested by single- and double-strand breaks in epidermal and dermal skin cells. Furthermore, several studies have shown that HT inhibits leukocyte and macrophage activation, as well as their subsequent infiltration into epidermal and dermal skin cells. HT’s modulation of immune function helps reduce the inflammatory processes associated with radiation dermatitis.

n-3 and n-6 Polyunsaturated Fatty Acids (PUFAs)

The stratum corneum is composed of epidermal cell remnants surrounded by a combination of biological lipids. The epidermal cells producing these remnants require certain amino acids to sustain stratum corneum formation, while the lipid barrier requires specific PUFAs to maintain stratum corneum integrity. A mixture of sphingolipids, cholesterol, and free fatty acids forms the intercellular membrane bilayers of the stratum corneum which regulate barrier function. PUFAs have also been shown to reduce or prevent numerous side effects associated with radiotherapy, including radiation dermatitis.

In particular, linolenic (n-3) and linoleic (n-6) PUFAs were found to protect against radiation dermatitis while potentiating radiation treatment via lipid peroxidation. The fatty acids’ effect on tumor growth depends on the balance between n-3 and n-6 PUFAs and antioxidants. The proper formulation of potent antioxidants, n-3 and n-6 PUFAs significantly enhances radiotherapy while preventing fatty acid-induced oxidative stress on epidermal and dermal skin cells. PUFAs play important roles as regulators of the complex inflammatory processes established shortly after radiation-induced skin injury. PUFAs exert their functions in the form of protective phospholipids anchored in epidermal cell membranes or as soluble lipoic mediators of the inflammatory response. Linolenic n-3 fatty acids specifically inhibit proinflammatory interleukin-1, interleukin-6 and tumor necrosis factor-alpha (TNFα) production. Modulating the balance of lipid inflammatory mediators is an extremely valuable treatment for inflammatory skin disorders such as radiation dermatitis. Both n-3 and n-6 PUFAs balance lipid mediators and improve the reconstitution of epithelial integrity following skin injury.

There exist numerous n-3 and n-6 PUFA sources, several of which significantly protect against radiation-induced tissue damage. Canola oil has been reported as being one of the most potent antimutagenic compounds available for topical administration. Canola oil induces intracellular oxidative stress and apoptosis in human cancer cells while inhibiting inflammatory leukocyte activity and subsequent skin irritation. Similarly, safflower oil protects against normal cell damage. Olive oil is another PUFA that has been shown to exhibit substantial anticancer and antioxidative effects. In addition, olive oil specifically prevents radiation-induced skin injury by protecting normal DNA and sustaining skin cell homeostasis. Altogether, the proper balance of certain PUFAs provides important protection against radiation dermatitis.

Dr. Darlene McCord

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