Chitosan oligosaccharides ameliorate severe acute pancreatitis-associated intestinal mucosal injury via the modulation of TLR4/NF-κB/NRLP3 pathway

Severe acute pancreatitis (SAP) is an abrupt inflammation of the pancreas, frequently associated with intestinal barrier injury. Chitosan oligosaccharides (COS) possess anti-inflammatory effects observed in multiple disease contexts. The protective effect of COS (200 mg/kg) was evaluated in a mouse model of SAP induced via intraperitoneal injection of cerulein (100 μg/kg) and lipopolysaccharide (5 mg/kg) in this study. The results shown that COS reduced serum amylase and lipase levels and alleviated pancreatic and ileal pathological damage in SAP mice. COS effectively diminished pancreatic and ileal pro-inflammatory cytokines levels (MCP-1, IL-1β, IL-6, and TNF-α), ileal cell apoptosis and intestinal permeability, and bacterial translocation as well. Moreover, COS administration restored the intestinal epithelial junction proteins expression (Claudin-1, Occludin, and ZO-1) and enhanced Paneth cell functional recovery. Mechanically, COS alleviated SAP-associated inflammatory response by suppressing the TLR4/NF-κB/NRLP3 pathway, which suggest that COS intervention may be a potential strategy to protect against SAP. • COS attenuated SAP-induced pancreatic damage (edema, necrosis, inflammation). • COS suppressed systemic cytokines (TNF-α, IL-1β, IL-6, MCP-1) and serum amylase/lipase. • COS reduced bacterial translocation, restored intestinal permeability/barrier integrity, and recovered Paneth cell function. • COS acted by suppressing the TLR4/NF-κB/NLRP3 pathway and modulating the intestinal barrier via apoptosis inhibition.