| Neuroprotective effects of alpha-lipoic acid and its positively charged amide analogue. | |
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MedLine Citation:
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PMID: 10401605 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Elevated levels of extracellular glutamate have been linked to reactive oxygen species mediated neuronal damage and brain disorders. Lipoic acid is a potent antioxidant that has previously been shown to exhibit neuroprotection in clinical studies. A new positively charged water soluble lipoic acid amide analog, 2-(N,N-dimethylamine) ethylamido lipoate HCl (LA-plus), with a better cellular reduction and retention of the reduced form was developed. This novel antioxidant was tested for protection against glutamate induced cytotoxicity in a HT4 neuronal cell line. Glutamate treatment for 12 h resulted in significant release of LDH from cells to the medium suggesting cytotoxicity. Measurement of intracellular peroxides showed marked (up to 200%) increase after 6 h of glutamate treatment. Compared to lipoic acid, LA-plus was more effective in (1) protecting cells against glutamate induced cytotoxicity, (2) preventing glutamate induced loss of intracellular GSH, and (3) disallowing increase of intracellular peroxide level following the glutamate challenge. The protective effect of LA-plus was found to be independent of its stereochemistry. The protective function of this antioxidant was synergistically enhanced by selenium. These results demonstrate that LA-plus is a potent protector of neuronal cells against glutamate-induced cytotoxicity and associated oxidative stress. |
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Authors:
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O Tirosh; C K Sen; S Roy; M S Kobayashi; L Packer |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Free radical biology & medicine Volume: 26 ISSN: 0891-5849 ISO Abbreviation: Free Radic. Biol. Med. Publication Date: 1999 Jun |
Date Detail:
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Created Date: 1999-09-16 Completed Date: 1999-09-16 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1418-26 Citation Subset: IM |
Affiliation:
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Department of Molecular and Cell Biology, University of California, Berkeley 94720-3200, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line Cytoprotection Drug Evaluation, Preclinical Electrochemistry Free Radical Scavengers / pharmacology Glutamic Acid / metabolism Hippocampus / cytology, drug effects*, metabolism Mice Molecular Conformation Neurons / drug effects*, metabolism Neuroprotective Agents / pharmacology* Thioctic Acid / analogs & derivatives*, pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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DK 50430/DK/NIDDK NIH HHS; GM 27345/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Free Radical Scavengers; 0/LA-Plus; 0/Neuroprotective Agents; 56-86-0/Glutamic Acid; 62-46-4/Thioctic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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