Effects of Castanospermine on Inflammatory Response in a Rat Model of Experimental Severe Acute Pancreatitis.

Abstract

BACKGROUND AND AIMS:

Acute pancreatitis (AP) is an acute inflammatory disorder characterized by autodigestion of pancreatic tissue resulting in local pancreatic injury or systemic inflammatory response. Castanospermine (CAST) is an alkaloid from the Castanospermum australe, known as an anti-inflammatory agent and immunosuppressant in animal experiments. However, whether CAST can attenuate AP remains unclear. This study investigated the effects of CAST on sodium taurocholate (STC)-induced severe acute pancreatitis (SAP) in rats and the pertinent mechanism.

METHODS:

SAP was induced in rats by a retrograde infusion of 5% STC (1 mL/kg) into the biliopancreatic duct. CAST (10, 50, 100, 200 and 500 mg/kg body weight) was then administered via intraperitoneal injection. Measurement of serum amylase, lipase, alanine aminotransferase, aspartate aminotransferase, creatinine, blood urea nitrogen and pancreas pathological grading was used to estimate the severity of pancreatitis. Serum levels of interleukin (IL) -1β, IL-6 and IL-10 were studied by enzyme-linked immunosorbent assay (ELISA). Nuclear factor (NF) -κB, tumor necrosis factor (TNF)-α, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 expression in pancreas was evaluated by immunohistochemistry.

RESULTS:

Administration of CAST following SAP was found to ameliorate the acute pancreatic tissue injury and exhibit a more appropriately protective effect at the dose of 200 mg/kg body weight. In addition, it decreased the interleukin production in serum and NF-κB activation, TNF-α, ICAM-1 and VCAM-1 up-regulation in pancreatic tissue.

CONCLUSIONS:

Our study demonstrated that CAST exerts a protective effect on SAP in rats.

• Authors: Yu-Pu Hong, Chen Chen, Wen-Yi Guo, Liang Zhao, Fang-Chao Mei, Ming-Wei Xiang, Wei-Xing Wang
• Journal: Archives of medical research (Arch Med Res) Vol. 47 Issue 6 Pg. 436-445 (Aug 2016) ISSN: 1873-5487 [Electronic] United States
• PMID: 27986123 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• IL10 protein, human
• Indolizines
• Interleukin-1beta
• Interleukin-6
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• Interleukin-10
• Taurocholic Acid
• castanospermine

Topics

• Acute Disease
• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Indolizines (therapeutic use)
• Intercellular Adhesion Molecule-1 (metabolism)
• Interleukin-10 (blood)
• Interleukin-1beta (blood)
• Interleukin-6 (blood)
• Male
• NF-kappa B (metabolism)
• Pancreas (drug effects, metabolism)
• Pancreatitis (chemically induced, metabolism, prevention & control)
• Rats, Sprague-Dawley
• Taurocholic Acid
• Tumor Necrosis Factor-alpha (metabolism)
• Up-Regulation
• Vascular Cell Adhesion Molecule-1 (metabolism)