title: Ascidian (chordate-tunicate) and mammalian heparin enemas attenuate experimental diversion colitis.
abstract: OBJECTIVE
  We sought to investigate whether mammalian or ascidian Styela plicata heparin enemas could diminish inflammation in experimental diversion colitis.
  
  
  METHODS
  Wistar-specific pathogen-free rats were submitted to a Hartmann's end colostomy and treated with enemas containing mammalian or Styela plicata heparin, or saline. Enemas were administered 3 times a week in the excluded colon segment from 4 to 8 weeks after operation. The effect of treatment was evaluated using video-endoscopic and histologic scores, measuring the cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and transforming growth factor-β production in organ cultures by enzyme-linked immunosorbent assay, quantifying T cells and macrophages, and investigating nuclear factor-kappa B (NF-κB) and external mitogen-activated protein kinase (pERK) activation.
  
  
  RESULTS
  Treatment with either mammalian or Styela plicata heparins decreased colonoscopic and histologic scores (P < .02) and restored the densities of collagen fibers and the number of goblet cells (P < .03) in the diverted colon. Both heparin treatments decreased the accumulation of T cells and macrophages (P < .03), and the activation of NF-κB and pERK (P < .04) in the diverted colon. The high levels of cytokines IL-1β, TNF-α, and IL-6 from the diversion colitis explants decreased (P < .05) to near normal values with heparin treatments.
  
  
  CONCLUSIONS
  The improvement of experimental diversion colitis with heparin treatments indicates the anti-inflammatory effect of these compounds, even after topical administration. Further studies with the nonhemorrhagic heparin obtained from the invertebrate Styela plicata will be necessary to confirm its efficacy for the treatment of human diversion colitis and possibly other forms of colitis.
authors.affiliation: Centro de Cirurgia Experimental, Programa de Pós-Graduação em Ciências Cirúrgicas, Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Valter
authors.initials: V
authors.lastname: Alvarenga
authors.affiliation: Centro de Cirurgia Experimental, Programa de Pós-Graduação em Ciências Cirúrgicas, Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Rodrigo Goulart
authors.initials: RG
authors.lastname: Pacheco
authors.affiliation: Centro de Cirurgia Experimental, Programa de Pós-Graduação em Ciências Cirúrgicas, Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Christiano Costa
authors.initials: CC
authors.lastname: Esposito
authors.affiliation: Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Buongusto
authors.affiliation: Laboratório de Imunologia Celular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Morgana Teixeira Lima
authors.initials: MT
authors.lastname: Castelo-Branco
authors.affiliation: Departamento de Patologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Kalil
authors.initials: K
authors.lastname: Madi
authors.affiliation: Instituto de Bioquímica Médica, Programa de Glicobiologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Faculdade de Medicina Campus UFRJ-Macaé, da Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Celso R
authors.initials: CR
authors.lastname: Belmiro
authors.affiliation: Instituto de Bioquímica Médica, Programa de Glicobiologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Mauro Sergio Gonçalves
authors.initials: MS
authors.lastname: Pavão
authors.affiliation: Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: hsouza@hucff.ufrj.br.
authors.forename: Heitor Siffert Pereira
authors.initials: HS
authors.lastname: de Souza
authors.affiliation: Centro de Cirurgia Experimental, Programa de Pós-Graduação em Ciências Cirúrgicas, Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Alberto
authors.initials: A
authors.lastname: Schanaider
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage*; D003092:Colitis / Q000188:drug therapy* / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003113:Colonoscopy; D004195:Disease Models, Animal; D004733:Enema; D005260:Female; D006493:Heparin / Q000008:administration & dosage*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014561:Urochordata
chemical_list: D000925:Anticoagulants; D006493:Heparin; D003094:Collagen