Inhibition of nitric oxide synthesis in primary cultured mouse hepatocytes by α-lipoic acid

Jun Feng Liang, Toshihiro Akaike

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Recent work shows that septic or endotoxic shock is associated with lipopolysaccharide and cytokine mixture-induced nitric oxide (NO) synthesis in liver. Here we found that DL-α-lipoic acid inhibited but other thiol- containing antioxidants such as glutathione and N-acetylcysteine enhanced lipopolysaccharide and cytokine mixture (referred as LPS/CM)-induced NO synthesis in hepatocytes. The inhibitory action of α-lipoic acid on hepatocyte NO synthesis was as potent as that of N(G)-monomethyl-L-arginine without obvious cytotoxicity. Deletion by diethylmaleate or inhibition by buthionine sulfoximine of intracellular glutathione caused a significant decrease in hepatocyte NO synthesis, implying that increased intracellular reduced glutathione levels could not be the reason for α-lipoic acid inhibited NO synthesis. α-Lipoic acid inhibition of NO synthesis seems to be from α-lipoic acid improved carbohydrate metabolism in hepatocytes. Since α-lipoic acid is an essential compound existing naturally in physiological systems, it may serve as both a research and therapeutic agent for sepsis.

Original languageEnglish
Pages (from-to)53-60
Number of pages8
JournalChemico-Biological Interactions
Volume124
Issue number1
DOIs
StatePublished - 3 Jan 2000

Keywords

  • Antioxidant
  • Hepatocyte
  • Lipopolysaccharide
  • Nitric oxide
  • α-Lipoic acid

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