A study of the beneficial role of thiol antioxidant supplementation in various forms of glutathione deficiency.

摘要

Oxidative stress plays a major role in the pathology of numerous disorders afflicting humans, ranging from neurodegenerative diseases, to cancer, and heavy metal toxicity. Scientists are on the constant lookout for new and better antioxidants that have the ability to slow, if not stop the harmful degenerative effects of free radicals in oxidative stress related disorders. Both synthetic and naturally occurring compounds are being constantly screened for their antioxidant properties. This study attempted to evaluate the abilities of a thiol antioxidant, N-Acetylcysteine amide (NACA), to protect cells from the harmful effects of glutathione depletion in two different models of oxidative stress. The first model represented oxidative stress processes in age-related macular degeneration. This part of the study focused on the protective effects of NACA on t-butyl hydroperoxide (tBHP) induced oxidative damage in retinal pigment epithelial cells, ARPE-19. The second model of glutathione deficiency used was fibroblast cell lines derived from patients with hereditary glutathione synthetase enzyme deficiency. Thirteen different fibroblasts were investigated for their basal levels of glutathione, following which selected cell lines were treated with NACA to assess if thiol supplementation can elevate GSH levels in these cells. In addition, this study also explored a newly developed model for glutathione deficiency, i.e., the glutathione synthetase knockout mouse model. The antioxidant status of this mouse model was explored in detail, by measurement of numerous oxidative stress parameters in various tissues. Overall, the results from this study show that NACA does, indeed protect cells from the deleterious effects of loss in cellular glutathione. NACA supplementation may thus prove beneficial in a number of oxidative stress-related disorders.