Gut lipopolysaccharide binding by colistin decreases tissue injury during severe acute pancreatitis

Abstract

Introduction: Gut derived lipopolysaccharide (LPS) is important factor in development of single and multiple organ failure during severe acute pancreatitis (SAP). Aims: To evaluate the effects of enteral administration of colistin (CS) on preventing LPS absorption from gut during SAP. Materials & methods: In 200 rats SAP was induced by L-arginine injection. Enteral administration of 2 mg/kg of CS every 6 h performed in CS high dose (CHD) group (n 1⁄4 10), 1 mg/kg every 12 h in CS low dose (CLD) group (n1⁄4 10), 1 mg/kg included in chitosan nanoparticles every 12 h in CS nanoparticles (CNP) group (n 1⁄4 10). Levels of LPS, sCD14, TNFa, morphological changes in pancreas, other internal organs and intestinal microbiota have been studied during 7 days. Results: CS administration caused reduction of LPS levels in faeces for 100-1000 times in all treated groups, but in mucus such events appeared only in CNP group. LPS concentrations in portal and system blood were similar to sham control level in CNP and elevated 2 and 4-5 times in CHD and CLD animals. Administration of CS reduced amounts of sCD14 and TNFa in all treatment cases, but only in CNP group there levels were closed to sham animals. Tissue injuries were much lesser in case of CNP group. Conclusion: Selective binding of gut-derived LPS during SAP by enteral administration of CS effectively decreases tissue injury in case it is incorporated to mucoadhesive nanoparticle delivery system or applied in high dose regimen. Abstracts / Pancreatolog S2