Thiol Antioxidants

Thiols share an oxidizable sulphhydryl (SH) group. Glutathione (GSH) is a tripeptide (Fig. 3) whose SH group at the cysteine can be oxidized, forming a disulphide (GSSG) with another GSH molecule. Physiologically, more than 90% of the GSH is in the reduced form. Glutathione peroxidases use GSH oxidation to reduce H2O2 and other water soluble peroxides. The synthesis of GSH by the human cell is stimulated by N-acetyl-cysteine (NAC), which is hydrolyzed to cysteine intracellularly. Moreover NAC acts as an antioxi-

Figure 3 Chemical structures of thiols: (a) GSH consisting of glycine, cysteine, and glutamic acid; (b) lipoic acid as in its oxidized form as a disulphide.

dant itself. Lipoic acid (1,2-dithiolane-3-pentanonic acid or thioctic acid, LA) is a cofactor of multienzyme complexes in the decarboxylation of a-keto acids. Applied as the oxidized dithiol dehydrolipoic acid (DHLA) it is taken up by cells and is reduced by mitochondrial and cytosolic enzymes (NAD(P)H dependent). It thereby forms an efficient cycle, since it can in turn regenerate GSSG to GSH and stimulate the GSH synthesis by improving cysteine utilization [38].

General provisos in the use of thiols in skin applications are the typical smell and the poor solubility of LA in aqueous solutions below pH 7. Yet, several thiol agents have been tested for protective effects in the skin. For oral as well as topical application in mouse models, GSH-ethylesters and GSH-isopropylesters proved to be more efficient than free GSH. Oral supplementation decreased the formation of UV-induced tumors [39] and the formation of sunburn cells [40]. Topical treatment partially inhibited UV-induced im-munosupression [41]. NAC was able to reduce UVA-induced DNA damage in fibroblasts [42] and protected mice against UVB-induced immunosuppression after topical application [43] in a mode that did not involve de novo GSH synthesis [44]. Lipoic acid was demonstrated to penetrate into mouse skin [45], while oral supplementation of lipoic acid has actually been shown to have an anti-inflammatory effect in mice [46], to prevent symptoms of vitamin E deficiency in vitamin E-deficient mice [47], and vitamin C and E deficiency in guinea pigs [48].

Cure Tennis Elbow Without Surgery

Cure Tennis Elbow Without Surgery

Everything you wanted to know about. How To Cure Tennis Elbow. Are you an athlete who suffers from tennis elbow? Contrary to popular opinion, most people who suffer from tennis elbow do not even play tennis. They get this condition, which is a torn tendon in the elbow, from the strain of using the same motions with the arm, repeatedly. If you have tennis elbow, you understand how the pain can disrupt your day.

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