There is extensive evidence that Se prevents the accumulation of free radicals, thereby protecting from UV damage and fortifying the immune system. Se is an essential cofactor for the intracellular antioxidant enzymes GPX and thioredoxin reductase (TDR) (84). Se is incorporated covalently into proteins of this GPX-TDR family of selenoenzymes (85) as well as into other selenoproteins (86) that may mediate some of the protective effects of Se on UVB-induced cell damage. Through the activities of these enzymes, Se quenches free radicals which would otherwise damage DNA proteins and cellular membranes.
Precise molecular mechanisms are being extensively researched. Protection of keratinocyte DNA was demonstrated by decreased 8-hydroxy-2-deoxyguanosine formation after UV irradiation (87,88), though there was no protection from pyrimidine dimer formation (87). There is evidence that L-selenomethionine (SeMet) induces a DNA repair response in human fibroblasts in vitro (89), perhaps by redox regulation of the DNA repair branch of the p53 pathway (90). In fact, different chemical forms of Se differently modify p53 (each by phosphorylation of specifc cysteine and threonine residues) to induce DNA repair or apoptosis after DNA damage (91). Further cellular protection has been
demonstrated by a decrease in UVB-induced lipid peroxides in keratinocytes (87) and fibroblasts (92) by pre-treatment with SeMet.
Finally, in vitro both SeMet and Se sulfide protect keratinocytes (87,93,94), melanocytes (87,93), and apoptosis (87,95). Interestingly, keratinocytes have twice the GPX activity of fibroblasts which correlates with greatly increased resistance to UVA – induced cell death for keratincytes (96). The fact that Se may prevent UV-induced cell death by p53-independent pathways is evidenced by the demonstration that pre-incubation of cultured human keratinocytes with sodium selenite or SeMet protects from UVB – induced apoptosis without decreasing levels of UVB-induced p53 (97).
Se may also be of particular importance in pigmentation through TDR. Located on keratinocyte membranes, TDR prevents UV oxidation of thioredoxin (which would otherwise enhance tyrosinase synthesis of dihydroxyphenylalanine, the precursor of melanin) (98,99).
Se has other advantageous action on the skin. Clinically, a direct anti-inflammatory effect by oral sodium selenite in Selye granuloma induction in rats was demonstrated (100). This anti-inflammatory action might be a direct result of decreased oxidative damage to cell membranes.
Finally, Se also increases cellular immune responses by several mechanisms, including increasing interleukin IL-2 receptor function (101-103) (thus making cells more resistant to oxidative stress) and through enhanced production of eicosanoids (101).