title: Protective effects of fucoidan, a P- and L-selectin inhibitor, in murine acute pancreatitis.
abstract: OBJECTIVE
  The objective of this study was to investigate the potential protective effects of fucoidan, an L- and P-selectin modulator, in 2 murine models of acute pancreatitis.
  
  
  METHODS
  Acute pancreatitis was induced in mice either by the retrograde infusion of taurolithocholic acid sulfate into the pancreatic duct or by intraperitoneal injections of cerulein (50 μg/kg per hour). The experimental groups received fucoidan (25 mg/kg, intravenously) before pancreatitis induction, whereas control groups received only saline. After 24 hours, serum amylase, lipase, interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and nitrite were measured. In addition, myeloperoxidase (MPO) activity (lung and pancreas) and histological assessment (pancreas) were determined.
  
  
  RESULTS
  Serum amylase, lipase, nitrite, TNF-α, and IL-1β, and pancreatic and lung MPO were increased in both taurolithocholic acid sulfate and cerulein acute pancreatitis compared with the respective control groups. Fucoidan significantly decreased the augmented levels of amylase, lipase, pancreatic and lung MPO, TNF-α, IL-1β, and nitrite in both models. Pancreas histological changes observed in both acute pancreatitis models were significantly attenuated by fucoidan.
  
  
  CONCLUSIONS
  Fucoidan reduced the severity of acute pancreatitis in mice by decreasing neutrophil infiltration and systemic inflammation, suggesting that modulation of selectins may constitute a promising therapeutic approach.
authors.affiliation: From the Departments of *Physiology and Pharmacology and †Morphology, Institute of Biomedicine of Brazilian Semi-Arid, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil; and ‡NIHR Pancreas Biomedical Research Unit and §Department of Cellular & Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Ana C S
authors.initials: AC
authors.lastname: Carvalho
authors.forename: Rhamon B
authors.initials: RB
authors.lastname: Sousa
authors.forename: Álvaro Xavier
authors.initials: ÁX
authors.lastname: Franco
authors.forename: José Victor Gomes
authors.initials: JV
authors.lastname: Costa
authors.forename: Luara Manuela
authors.initials: LM
authors.lastname: Neves
authors.forename: Ronaldo A
authors.initials: RA
authors.lastname: Ribeiro
authors.forename: Robert
authors.initials: R
authors.lastname: Sutton
authors.forename: David N
authors.initials: DN
authors.lastname: Criddle
authors.forename: Pedro M G
authors.initials: PM
authors.lastname: Soares
authors.forename: Marcellus H L P
authors.initials: MH
authors.lastname: de Souza
mesh_terms: D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D002108:Ceruletide; D053583:Interleukin-1beta / Q000097:blood; D019041:L-Selectin / Q000378:metabolism*; D008049:Lipase / Q000097:blood; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects; D009573:Nitrites / Q000097:blood; D019007:P-Selectin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D009195:Peroxidase / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology*; D013658:Taurolithocholic Acid; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000897:Anti-Ulcer Agents; D053583:Interleukin-1beta; D009573:Nitrites; D019007:P-Selectin; D011134:Polysaccharides; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; D013658:Taurolithocholic Acid; D002108:Ceruletide; C007789:fucoidan; D009195:Peroxidase; D008049:Lipase; D000681:Amylases