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 language | English |
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Pages (from-to) | 53-60 |
Number of pages | 8 |
Journal | Chemico-Biological Interactions |
Volume | 124 |
Issue number | 1 |
DOIs | |
State | Published - 3 Jan 2000 |
Keywords
- Antioxidant
- Hepatocyte
- Lipopolysaccharide
- Nitric oxide
- α-Lipoic acid