| Summary: | 碩士 === 實踐大學 === 食品營養研究所 === 93 === Sepsis is caused by serious bacterial infections that induced severe systemic immune response and high mortality rate. Lipopolysaccharide (LPS), the main component of the outer cell wall in all Gram-negative bacteria, triggers severe pathologic alternations,such as systemic inflammation, mupltiple organdysfunction (MOD), and death in clinical studies. Sialic acid, a family of nine carbon 2-keto-3-deoxy sugars, can be used for building up our immunization, as inhibitors of influenza viruses, and immunoregulator and effector in tumor antimetastasis. However, the antioxidant activity and the therapeutic role of sialic acid on acute endotoxemia remain to be explored.
In in vitro experiment, we explored the effect of sialic acid on scavenging O2-., H2O2, HOCl, and NO activity by a chemiluminescence analyzer and the binding effect to lipopolysaccharide (LPS) and Lipid A (LPA) by a biosensor.In the in vivo experiment, we assessed the effect of sialic acid on (LPS) induced acute endotoxemia. We evaluated in vitro (blood and bile) and in vivo (liver) reactive oxygen species (ROS) responses, hepatic and renal hemodynamics, plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine, blood urea nitrogen (BUN), plasma endotoxin cytokine array, tissue western blot analysis in the septic rats treated with sialic acid.
Our in vitro results showed that sialic acid can directly scavenge O2-., H2O2, HOCl, and NO activity and bind to LPS and LPA, suggesting a therapeutic role in LPS-induced acute endotoxinemia and oxidative stress. In acute endotoxiema, LPS increased the ROS level in blood, bile, and liver, increased plasma ALT and AST level, serum creatinine and BUN level as well as plasma monocyte chemoattractant protein-1 (MCP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1), TNF-α, IL-6, IL1-ß amount. Intravenous 10 mg sialic acid decreased the ROS level, reduced plasma ALT and AST and BUN and creatinine level, reduced cytokine concentration, and ameliorated hepatic and renal pathology. By western blotting analysis, we found that the antioxidant and anti-apoptotic proteins like CuZn-superoxide dismutase, Mn-superoxide dismutase, heat shock protein 70, and Bcl-2 protein were all enhanced and the proapoptotic Bax protein was decreased after sialic acid treatment. In conclusion, LPS can induced acute endotoxinema and increase oxidative stress. Sialic acid can counteract LPS-induced acute endotoxinema and oxidative stress by the possible mechanisms of a direct scavenging ROS activity and an upregulation of antioxidant and antiapoptotic proteins.
Key words：Acute endotoxiema; Lipopolysaccharide; Sialic acid; Reactive oxygen species
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