Document Detail


The pharmacology of the antioxidant lipoic acid.
MedLine Citation:
PMID:  9378235     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. Lipoic acid is an example of an existing drug whose therapeutic effect has been related to its antioxidant activity. 2. Antioxidant activity is a relative concept: it depends on the kind of oxidative stress and the kind of oxidizable substrate (e.g., DNA, lipid, protein). 3. In vitro, the final antioxidant activity of lipoic acid is determined by its concentration and by its antioxidant properties. Four antioxidant properties of lipoic acid have been studied: its metal chelating capacity, its ability to scavenge reactive oxygen species (ROS), its ability to regenerate endogenous antioxidants and its ability to repair oxidative damage. 4. Dihydrolipoic acid (DHLA), formed by reduction of lipoic acid, has more antioxidant properties than does lipoic acid. Both DHLA and lipoic acid have metal-chelating capacity and scavenge ROS, whereas only DHLA is able to regenerate endogenous antioxidants and to repair oxidative damage. 5. As a metal chelator, lipoic acid was shown to provide antioxidant activity by chelating Fe2+ and Cu2+; DHLA can do so by chelating Cd2+. 6. As scavengers of ROS, lipoic acid and DHLA display antioxidant activity in most experiments, whereas, in particular cases, pro-oxidant activity has been observed. However, lipoic acid can act as an antioxidant against the pro-oxidant activity produced by DHLA. 7. DHLA has the capacity to regenerate the endogenous antioxidants vitamin E, vitamin C and glutathione. 8. DHLA can provide peptide methionine sulfoxide reductase with reducing equivalents. This enhances the repair of oxidatively damaged proteins such as alpha-1 antiprotease. 9. Through the lipoamide dehydrogenase-dependent reduction of lipoic acid, the cell can draw on its NADH pool for antioxidant activity additionally to its NADPH pool, which is usually consumed during oxidative stress. 10. Within drug-related antioxidant pharmacology, lipoic acid is a model compound that enhances understanding of the mode of action of antioxidants in drug therapy.
Authors:
G P Biewenga; G R Haenen; A Bast
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  General pharmacology     Volume:  29     ISSN:  0306-3623     ISO Abbreviation:  Gen. Pharmacol.     Publication Date:  1997 Sep 
Date Detail:
Created Date:  1997-11-10     Completed Date:  1997-11-10     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  7602417     Medline TA:  Gen Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  315-31     Citation Subset:  IM    
Affiliation:
Leiden/Amsterdam Center for Drug Research, Vrije Universiteit, Department of Pharmacochemistry, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / metabolism,  pharmacokinetics,  pharmacology*
Humans
Oxidative Stress / drug effects
Thioctic Acid / metabolism,  pharmacokinetics,  pharmacology*
Chemical
Reg. No./Substance:
0/Antioxidants; 62-46-4/Thioctic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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