Journal Article

Pretreatment with chitosan oligosaccharides attenuate experimental severe acute pancreatitis via inhibiting oxidative stress and modulating intestinal homeostasis

Hu, Jun-hui, Zeng, Yue, Mei, Qi-xiang, Wang, Xing-peng, Huang, Chun-lan, Lu, Ying-ying, Huang, Ze-hua, Fan, Jun-jie

2021

Overview

Severe acute pancreatitis (SAP) is a severe acute abdominal disease. Recent evidence shows that intestinal homeostasis is essential for the management of acute pancreatitis. Chitosan oligosaccharides (COS) possess antioxidant activity that are effective in treating various inflammatory diseases. In this study we explored the potential therapeutic effects of COS on SAP and underlying mechanisms. Mice were treated with COS (200 mg·kg −1 ·d −1 , po ) for 4 weeks, then SAP was induced in the mice by intraperitoneal injection of caerulein. We found that COS administration significantly alleviated the severity of SAP: the serum amylase and lipase levels as well as pancreatic myeloperoxidase activity were significantly reduced. COS administration suppressed the production of proinflammatory cytokines (TNF-α, IL-1β, CXCL2 and MCP1) in the pancreas and ileums. Moreover, COS administration decreased pancreatic inflammatory infiltration and oxidative stress in SAP mice, accompanied by activated Nrf2/HO-1 and inhibited TLR4/NF-κB and MAPK pathways. We further demonstrated that COS administration restored SAP-associated ileal damage and barrier dysfunction. In addition, gut microbiome analyses revealed that the beneficial effect of COS administration was associated with its ability to improve the pancreatitis-associated gut microbiota dysbiosis; in particular, probiotics Akkermansia were markedly increased, while pathogenic bacteria Escherichia – Shigella and Enterococcus were almost eliminated. The study demonstrates that COS administration remarkably attenuates SAP by reducing oxidative stress and restoring intestinal homeostasis, suggesting that COS might be a promising prebiotic agent for the treatment of SAP. Supplementation of chitosan oligosaccharides(COS) could ameliorate severity of pancreatic injury, prevent intestinal barrier disruption and reduce inflammatory and oxidative injury in severe acute pancreatitis (SAP). The protective mechanism partly attributed to the reshaping of gut microbiota and TLR4 and Nrf2/HO-1 pathway.

• Publisher: Springer Singapore,Nature Publishing Group
• Subject: Abdominal diseases / Acute Disease / Animals / Antioxidants / Apoptosis - drug effects / Biomedical and Life Sciences / Biomedicine / Chitin - analogs & derivatives / Chitin - therapeutic use / Chitosan / Chitosan - therapeutic use / Digestive system / Dysbacteriosis / Gastrointestinal Microbiome - drug effects / Gastrointestinal tract / Homeostasis / Homeostasis - drug effects / IL-1β / Immunology / Inflammatory diseases / Internal Medicine / Intestinal microflora / Intestine / Intestines - drug effects / Male / MAP kinase / Medical Microbiology / Mice / Mice, Inbred C57BL / Microbiomes / Microbiota / NF-κB protein / Oligosaccharides / Oligosaccharides - therapeutic use / Oxidative stress / Oxidative Stress - drug effects / Pancreas / Pancreas - drug effects / Pancreas - pathology / Pancreatitis / Pancreatitis - drug therapy / Pancreatitis - pathology / Peroxidase / Pharmacology/Toxicology / Probiotics / Signal Transduction - drug effects / Supplements / TLR4 protein / Toll-like receptors / Tumor necrosis factor-α / Vaccine