Inhibition of nitric oxide synthesis in primary cultured mouse hepatocytes by alpha-lipoic acid.
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-alpha-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 alpha-lipoic acid on hepatocyte NO synthesis was as potent as that of NG-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 alpha-lipoic acid inhibited NO synthesis. alpha-Lipoic acid inhibition of NO synthesis seems to be from alpha-lipoic acid improved carbohydrate metabolism in hepatocytes. Since alpha-lipoic acid is an essential compound existing naturally in physiological systems, it may serve as both a research and therapeutic agent for sepsis.
Liang
J F
JF
Department of Biomolecular Engineering, Tokyo Institute of Technology, Yokohama, Japan. junfeng@umich.edu
Akaike
T
T
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D010084:Oxidation-Reduction / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000502:physiology; D008063:Thioctic Acid / Q000494:pharmacology*
D008070:Lipopolysaccharides; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; D008063:Thioctic Acid