Antioxidant inhibition of skin inflammation induced by reactive oxidants: evaluation of the redox couple dihydrolipoate/lipoate.

Reactive oxygen species play an important role in mediating skin inflammation, and antioxidants may provide protection. We investigated the anti-inflammatory activity of natural antioxidants, such as superoxide dismutase, catalase, trolox (a water-soluble tocopherol analog) and the redox couple dihydrolipoate/lipoate in skin. Furthermore we compared the anti-inflammatory potency of natural R and racemic dihydrolipoate, as well as R and S lipoate. Skin inflammation in hairless mice was induced by intradermal injection of the hydrogen peroxide producing enzyme glucose oxidase (GOD) or by topical application of the prooxidant drug anthralin. Intradermal injection of the antioxidants inhibited skin inflammation caused by GOD (catalase, dihydrolipoate) and anthralin (trolox, superoxide dismutase, dihydrolipoate). There was no statistically significant difference between the anti-inflammatory activity of the natural R and racemic dihydrolipoate. R or S lipoate did not inhibit skin inflammation when injected intradermally. In feeding experiments, however, R lipoate significantly inhibited GOD-mediated skin inflammation, while S lipoate was only marginally protective. We conclude that (1) several natural antioxidants such as catalase, superoxide dismutase and dihydrolipoate have anti-inflammatory properties in dermatitis induced by reactive oxidants, (2) lipoate (oxidized dihydrolipoate) has skin anti-inflammatory activity when administered orally and (3) naturally occurring R lipoate is a more potent anti-inflammatory agent than the non-physiological S lipoate.