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Sialic Acid Reduces Acute Endotoxemia-induced Liver Dysfunction in the Rat.

Authors: Ho, CH  Hsu, SP  Yang, CC  Lee, YH  Chien, CT 
Citation: Ho CH, etal., Shock. 2008 Dec 4.
Pubmed: (View Article at PubMed) PMID:19060786
DOI: Full-text: DOI:10.1097/SHK.0b013e318197118e

Endotoxemia caused by lipopolysaccharides (LPS) is a life-threatening and inflammatory condition contributing to multiple organ failure. Virus or bacteria requires sialic acid (SA) for target cells binding. We suggest exogenous SA through masking or mediating the binding of LPS to the target cells may attenuate LPS-induced liver dysfunction and cecal ligation and puncture (CLP) induced shock. We found that SA can directly scavenge O2, H2O2, and NO activity by a chemiluminescence analyzer and bind to LPS with high affinity using surface plasmon resonance. Intravenous SA significantly increased plasma SA concentration within 4 hrs. We then assessed the potential effect of SA on LPS-induced acute endotoxemia in the rat. Intravenous LPS (10-50 mg/kg) dose-dependently increased plasma endotoxin, reactive oxygen species (ROS) in the blood, bile, and liver, increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level as well as TNF-alpha, monocyte chemoattractant protein-1 (MCP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1), IL1-beta and IL-6 amount in the rats. Thirty min after LPS stimulation, SA decreased LPS-enhanced endotoxin level, oxidative stress, ALT and AST level, cytokines concentration, and ameliorated histopathological alteration in the liver. We found that SA increased LPS-depressed Mn-superoxide dismutase, CuZn-superoxide dismutase and heat shock protein 70 and decreased LPS-enhanced iNOS and proapoptotic Bax protein expression in the liver by western blot. SA was given post-treatment to CLP rats and that the hypotensive effect was blunted for 6 hr. In conclusion, SA treatment can counteract LPS enhanced acute endotoxinema and oxidative injury via a direct scavenging ROS activity and neutralization potential.


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RGD Object Information
RGD ID: 2307004
Created: 2009-05-14
Species: All species
Last Modified: 2009-05-14
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.