title: Effects of Castanospermine on Inflammatory Response in a Rat Model of Experimental Severe Acute Pancreatitis.
abstract: OBJECTIVE
  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.affiliation: Department of General Surgery, Renmin Hospital, Wuhan University, Wuhan, PR China; Central Laboratory, Renmin Hospital, Wuhan University, Wuhan, PR China.
authors.forename: Yu-Pu
authors.initials: YP
authors.lastname: Hong
authors.affiliation: Department of General Surgery, Renmin Hospital, Wuhan University, Wuhan, PR China; Key Laboratory of Hubei Province for Digestive System Disease, Wuhan, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Renmin Hospital, Wuhan University, Wuhan, PR China.
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Guo
authors.affiliation: Department of General Surgery, Renmin Hospital, Wuhan University, Wuhan, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, Renmin Hospital, Wuhan University, Wuhan, PR China.
authors.forename: Fang-Chao
authors.initials: FC
authors.lastname: Mei
authors.affiliation: Department of General Surgery, Renmin Hospital, Wuhan University, Wuhan, PR China.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Xiang
authors.affiliation: Department of General Surgery, Renmin Hospital, Wuhan University, Wuhan, PR China. Electronic address: sate.llite@163.com.
authors.forename: Wei-Xing
authors.initials: WX
authors.lastname: Wang
mesh_terms: D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D007212:Indolizines / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D054836:Indolizidines
chemical_list: D000893:Anti-Inflammatory Agents; D007212:Indolizines; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D013656:Taurocholic Acid; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C508609:IL10 protein, human; C037806:castanospermine; D054836:Indolizidines
keywords: Acute pancreatitis; Adhesion molecules; Castanospermine; Cytokines; Inflammation