Redox homeostasis of albumin in relation to alpha-lipoic acid and dihydrolipoic acid

Abstract

Albumin represents the predominant circulating antioxidant agent in plasma exposed to continuous oxidative stress and a change in serum albumin structure accounts for its antioxidant properties. Alterations in the redox status of albumin may result in impairments of its biological properties. Alpha-lipoic acid (LA), a naturally occurring thiol compound found in virtually all species, is a potent antioxidant with high efficacy which is also involved in the chelation of metal ions, regeneration of antioxidants, and repair of oxidatively damaged proteins. In human body LA is rapidly reduced to dihydrolipoic acid (DHLA) after intake into the cell. Both, LA and DHLA are amphipathic molecules which act as antioxidants both in hydrophilic and lipophilic environments. The present study aimed to investigate the antioxidant/pro-oxidant effects of LA and DHLA due to their concentrations in metal-catalyzed protein oxidation (MCO) of human serum albumin (HSA). Progressive oxidative modification of albumin was found in MCO system by an increased content of protein hydroperoxides (POOH), protein carbonyl groups (PCO) which is the former's major breakdown product, and other protein oxidation markers such as advanced oxidized protein products (AOPP) and protein thiol groups (P-SH). The possible antioxidant protective effects of LA and DHLA were observed with 25 mu M and 50 mu M; DHLA being more influential. Protein oxidation parameters were found to be lower and P-SH levels seemed higher. However, prooxidant effects of both LA and DHLA came on the scene with increased concentrations of 75 mu M and 100 mu M where the latter seemed the most hazardous with contradicted results. It is clear that the loss of biological activity of human serum albumin by MCO system appears of medical relevance and if LA exerts similar effects seen in the present study, it is possible that cellular prooxidant activity can also result consuming this unique antioxidant in certain doses.