Lipoic and dihydrolipoic acids as antioxidants. A critical evaluation.
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 alpha 1-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 alpha-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 (O.2-) 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 alpha 1-antiproteinase and creatine kinase.
Scott
B C
BC
Neurodegenerative Diseases Research Centre, Kings College, University of London, UK.
Aruoma
O I
OI
Evans
P J
PJ
O'Neill
C
C
Van der Vliet
A
A
Cross
C E
CE
Tritschler
H
H
Halliwell
B
B
D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology; D016718:Arachidonic Acid; D001205:Ascorbic Acid; D001761:Bleomycin / Q000633:toxicity; D001921:Brain; D002417:Cattle; D004249:DNA Damage; D003855:Deoxyribose / Q000032:analysis; D016166:Free Radical Scavengers; D006861:Hydrogen Peroxide; D006997:Hypochlorous Acid / Q000037:antagonists & inhibitors / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D008081:Liposomes; D009211:Myoglobin / Q000737:chemistry / Q000187:drug effects; D013481:Superoxides; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000737:chemistry / Q000187:drug effects
D000975:Antioxidants; D016166:Free Radical Scavengers; D008081:Liposomes; D009211:Myoglobin; D000515:alpha 1-Antitrypsin; D001761:Bleomycin; D013481:Superoxides; D016718:Arachidonic Acid; D003855:Deoxyribose; D006997:Hypochlorous Acid; D008063:Thioctic Acid; C015144:dihydrolipoic acid; D006861:Hydrogen Peroxide; D001205:Ascorbic Acid