Lipoic and Dihydrolipoic Acids as Antioxidants. a Critical Evaluation

Abstract

A detailed evaluation of the antioxidant and pro-oxidant properties of lipoic acid (LA) and dihydrolipoic acid (DHLA) was performed. Both compounds are powerful scavengers of hypochlorous acid, able to protect α₁-antiproteinase against inactivation by HOCl. LA was a powerful scavenger of hydroxyl radicals (OH⁻) and could inhibit both iron-dependent OH' generation and peroxidation of ox-brain phospholipid liposomes in the presence of FeCl₃ -ascorbate, presumably by binding iron ions and rendering them redox-inactive. By contrast. DHLA accelerated iron-dependent OH⁻ generation and lipid peroxidation, probably by reducing Fe³⁺ to Fe²⁺. LA inhibited this pro-oxidant action of DHLA. However, DHLA did not accelerate DNA degradation by a ferric bleomycin complex and slightly inhibited peroxidation of arachidonic acid by the myoglobin-H₂O₂ system. Under certain circumstances, DHLA accelerated the loss of activity of α-antiproteinase exposed to ionizing radiation under a N₂O/O₂ atmosphere and also the loss of creatine kinase activity in human plasma exposed to gas-phase cigarette smoke. Neither LA nor DHLA reacted with superoxide radical (O₂⁻) or H₂O₂ at significant rates, but both were good scavengers of trichloromethylperoxyl radical (CCl₃O₂). We conclude that LA and DHLA have powerful antioxidant properties. However, DHLA can also exert pro-oxidant properties, both by its iron ion-reducing ability and probably by its ability to generate reactive sulphur-containing radicals that can damage certain proteins, such as α₁-antiproteinase and creatine kinase.

Key Words:

• Lipoic acid
• dihydrolipoic acid
• antioxidant
• superoxide
• hydroxyl radical
• lipid peroxidation
• hypochlorous acid
• trichloromethylperoxyl radical