Neuroprotective effects of α-lipoic acid and its positively charged amide analogue

Oren Tirosh, Chandan K. Sen, Sashwati Roy, Michael S. Kobayashi, Lester Packer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)1418-1426
Number of pages9
JournalFree Radical Biology and Medicine
Volume26
Issue number11-12
DOIs
StatePublished - Jun 1999
Externally publishedYes

Bibliographical note

Funding Information:
This research was supported by the National Institutes of Health Grants DK 50430 and GM 27345, and by the Alice Sussman fund of the Hebrew University of Jerusalem.

Keywords

  • Antioxidants
  • Free radicals
  • Neurotoxicity
  • Redox
  • Thioctic acid

Fingerprint

Dive into the research topics of 'Neuroprotective effects of α-lipoic acid and its positively charged amide analogue'. Together they form a unique fingerprint.

Cite this