Multiple protective mechanisms of alpha-lipoic acid in oxidation, apoptosis and inflammation against hydrogen peroxide induced toxicity in human lymphocytes

The naturally antioxidant and coenzyme, alphalipoic acid (alpha-LA), has gained considerable attention regarding different functions and therapeutically effective in treating oxidative stress-associated diseases in the human body. This study was designed to examine the protective effect of alpha-LA against H2O2-induced oxidative stress and apoptosis in human lymphoid cells. Human peripheral blood lymphocytes were preincubated with alpha-LA and then exposed to H2O2. After that, the viability of the cells, rate of apoptosis, oxidative stress biomarkers such as reactive oxygen species (ROS) and level of lipid peroxidation (LPO), and also tumor necrosis factor-alpha (TNF-alpha) were studied. Pretreatment of lymphocytes with alpha-LA, dramatically enhanced viability of the cells and decreased apoptosis. Investigation of caspases gives a clear picture of the mechanism by which alpha-LA decreases ROS and causes a reduction in apoptosis through caspase-9-dependent mitochondrial pathway. Furthermore, alpha-LA dose dependently decreased oxidative stress by a reduction in level of LPO, and the dose of 1000 mu M indicates a significant decrease (p < 0.01) in TNF-alpha level. Collectively, the present data show that alpha-LA is an ideal compound which has profound protective effects on oxidation, inflammation, and apoptosis. As a result, alpha-LA may indicate a new way toward the development of antioxidant therapy.