Evidence-based pathogenesis and treatment of ulcerative colitis: A causal role for colonic epithelial hydrogen peroxide

Figure 5 R-dihydrolipoic acid. A: R-dihydrolipoic acid (RDLA) is the reduced form of alpha lipoic acid (the oxidized form); B: The reducing equivalents of RDLA are provided by its two thiol groups (red circles) that are each capable of donating one electron. RDLA has a redox potential of -290 millivolts which is only exceeded by NADH and NADPH with a redox potential of -320 and -400 millivolts respectively[258]. Due to its very low (more negative) redox potential, RDLA can directly or indirectly reduce all other cellular antioxidants and many types of oxygen radicals[256]. These include vitamin-C, vitamin-E, glutathione, thioredoxin, glutaredoxin, catalase, glutathione peroxidase, and peroxiredoxin[258-261]. Alpha-lipoic acid is reduced by dehydrolipoamide dehydrogenase and Thioredoxin reductase, which use NADH and NADPH as reducing co-factors respectively[262]. The amphipathic nature of RDLA (lipid and water-soluble) allows it to diffuse throughout cellular compartments to transport reducing equivalents where needed and assist in neutralizing excess hydrogen peroxide. The elimination of excess intracellular cellular hydrogen peroxide is essential in order to restore cellular redox homeostasis and prevent ulcerative colitis relapse caused by extracellular diffusion of colonocyte hydrogen peroxide. Vit: Vitamin; DLD: Dehydrolipoamide dehydrogenase; TRx: Thioredoxin reductase; GSH: Glutathione.