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SELECTIVE BINDING OF GUT LIPOPOLYSACCHARIDE BY NANOPARTICLES LOADED WITH SODIUM COLISTIMETHATE IMPROVES OUTCOME OF ACUTE NECROTIZING PANCREATITIS
Oleksandr Rotar*1, Igor Khomiak2, Michael Fishbach1, Orest Konyk1, Vasyl Rotar1, Andrii Khomiak2
1General Surgery, Bukovinian State Medical University, Chernivtsi, Ukraine; 2 Pancreas Surgery and Bile Ducts Reconstruction Surgery, A.A. Shalimov National Institute of Surgery and Transplantology, Kyiv, Ukraine
Introduction: Gut derived lipopolysaccharide (LPS) is an important factor in development of distant organ damage during necrotizing pancreatitis (ANP).
Aims: To determine the role of LPS in the pathogenesis of tissue injury and evaluate the effects of LPS binding by enteral administrated chitosan nanoparticles (CN) loaded with sodium colistimethate (SC) on outcome of rats with ANP.
Materials and Methods: In 180 rats ANP was induced by L-arginine. Enteral administration of 3 mg/kg of SC every 8 h has beeen started just after SAP initiation in 1st group (n=60) and 1 mg/kg of SC included in CN every 12 h in 2nd group (n=60) and normal saline - in control group (n=60). Intestinal absorbance of LPS were studied by luminescent microsopy, levels of LPS and sCD14 were evaluated by ELISA in feces and blood during 5 days of ANP.
Results: The LPS level increased 2-5 times, sCD14 - 5-10 times (p<0,05) and mortality rate reached 20% in control animals. Enteral administration of the SC reduced in LPS levels in feces to less than 0,1-1,0% in all treated groups, but in mucus such events appeared only in 2nd group due to it intensive infiltration by CN. LPS concentrations and sCD14 in portal and system blood were similar to preoperation level in 2nd, but remained elevated 2-3 times in 1st group (p<0,05). Histological changes in internal organs were minimal in 2nd group as well as mortality rate.
Conclusions: CN loaded by SC effectively bind intestinal LPS, reduce its absorption and improve outcome of rats with SAP.
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