Topical a-LA with its metabolite DHLA could protect the skin from oxidative stress in several ways. Both a-LA and DHLA are highly effective antioxidants, as summarized in Table 1 (22). DHLA is actually the more potent form. Both successfully scavenge ROS in vitro and in vivo. However, pro-oxidant activity has been observed. This occurs when an antioxidant reacts with a ROS scavenger, forming a product that is more harmful than the scavenged ROS. Fortunately a-LA can act as an antioxidant against the pro-oxidant activity of DHLA (22). Both a-LA and DHLA further provide antioxidant activity by chelating Fe2C and Cu2C(a-LA) and Cd2C (DHLA) (22).
DHLA, unlike a-LA, has the capacity to regenerate the endogenous antioxidants vitamin E, vitamin C, gluthatione, and ubiquinol, as illustrated in Figure 3. This is clearly
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Table 1 Antioxidant Activity of a-Lipoic Acid and Dihydrolipoic Acid (DHLA)
Abbreviations: C, indicates activity; ++, indicates greater activity; —, indicates no activity. Source: Adapted from Ref. 22. |
of great importance for skin, since UV exposure directly depletes especially ubiquinone and vitamin E as well as vitamin C, thereby stressing the other linked antioxidants (154). Regeneration of these major membrane and cytosol antioxidants gives cascading protection. Increases in the other important antioxidants (intracellular glutathione and extracellular cysteine) are noted when a-LA is added to cell cultures (22). Vitamin E deficient animals do not show symptoms (weight loss, neuromuscular abnormalities) when supplemented with a-LA (155).
Although a-LA is a potent antioxidant, it provides no effective protection against UV – induced erythema or cell damage measured as sunburn cells (156). However, a-LA (but not DHLA) acts as an anti-inflammatory agent by reducing the production and inhibiting the binding of transcription factors such as nuclear factor-kappa B (NF-kappa B), thereby indirectly affecting the gene expression of inflammatory cytokines such as tumor necrosis factor-a (TNF-a) and interleukins (157). DHLA (but not a-LA) can repair oxidatively damaged proteins, which in turn regulate the activity of proteinase inhibitors such as a l-AP, an inflammatory modulator (158). As antioxidants, both a-LA and DHLA are directly antiinflammatory by virtue of their quenching oxidants secreted by leukocytes and macrophages at sites of inflammation (158).
a-LA may prove to retard and correct both intrinsic and extrinsic aging of the skin as well as other organs (159). By damaging DNA, the ROS continuously formed in normal metabolism may be largely responsible for the functional deterioration of organs with aging. A decrease in cellular protein and DNA as well as in a-LA levels has been measured in aged rat liver, kidney, and spleen (160). Supplementation with a-LA increases nucleic acid and protein levels in the elderly organs (160). Similarly, the age-related decrease of mitochondiral function in cardiac and brain cells can be improved with a-LA supplementation (161). Clearly, aging skin might similarly benefit.