Inhibitory effect of α-lipoic acid and its positively charged amide analogue on nitric oxide production in RAW 264.7 macrophages

Qiong Guo, Oren Tirosh, Lester Packer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


The aim of this study was to investigate the effect of the mitochondrial cofactor α-lipoic acid [R (+) LA] or its lipoamide analogue, 2-(N,N-dimethylamine) ethylamido lipoate [R (+) LA-plus], on nitric oxide (NO) production in RAW 264.7 macrophages. NO production from RAW 264.7 cells stimulated with 10 μg/mL of lipopolysaccharide and 50 U/mL of interferon-γ was measured directly by electron spin resonance using spin-trapping techniques. R (+) LA or R (+) LA-plus was found to inhibit NO production at pharmacologically relevant concentrations. However, in a cell-free chemical system, neither R (+) LA nor R (+) LA-plus was able to directly scavenge NO. Furthermore, in the presence of 2.5 or 25 mM glucose, the inhibitory effects of R (+) LA and R (+) LA-plus on NO production were decreased markedly, while they showed more potent inhibitory effects in the presence of 2 μM rotenone or 5 μg/mL of antimycin A, inhibitors of mitochondrial complex I and complex III, respectively. Glucose, rotenone, or antimycin A alone resulted in an increase of NO production. These results suggest that NO production in macrophages can be regulated by glucose and mitochondrial respiration, and that modulation of NO production by lipoic acid or lipoamide analogues in inflammatory situations is attributed not to their radical scavenging activity but to their redox properties.

Original languageAmerican English
Pages (from-to)547-554
Number of pages8
JournalBiochemical Pharmacology
Issue number5
StatePublished - 1 Mar 2001
Externally publishedYes

Bibliographical note

Funding Information:
This research was supported by BASF Aktiengesellschaft, Germany. The authors thank Drs. Hadi Moini and Sashwati Roy for helpful discussions.


  • Electron spin resonance
  • Glucose
  • Lipoic acid
  • Macrophages
  • Mitochondrial respiration
  • Nitric oxide


Dive into the research topics of 'Inhibitory effect of α-lipoic acid and its positively charged amide analogue on nitric oxide production in RAW 264.7 macrophages'. Together they form a unique fingerprint.

Cite this