title: Therapeutic effect of phenantroline in two rat models of inflammatory bowel disease.
abstract: BACKGROUND
  Phenantroline is a zinc-chelator that inhibits biological activities of matrix metalloproteinases (MMPs). Over-expression of MMPs can accelerate tissue destruction and disrupt subsequent tissue repair. The effects of phenantroline in two rat models of inflammatory bowel disease (IBD) are evaluated: transmural colitis induced by trinitrobenzensulphonic acid (TNBS) and distal colitis caused by dextran sulphate sodium (DSS).
  
  
  METHODS
  Transmural colitis was induced by TNBS in two groups of 15 rats each, and distal colitis was induced by DSS in two other groups of 15 rats each. Phenantroline was administered by oral gavage at 20 mg kg(-1) day(-1) to the test groups, whereas matched control groups received oral vehicle. On the last day of dosing, rats were subjected to intracolonic dialysis under anaesthesia for assessment of luminal eicosanoid release (PGE2, TXB2 and LTB4) and euthanized. Colons were removed and lesions were blindly scored according to macroscopic and histological scales. Myeloperoxidase (MPO) activity was measured in homogenates of colonic tissue.
  
  
  RESULTS
  In the TNBS model, phenantroline treatment significantly reduced colonic strictures; in the DSS model, phenantroline significantly decreased scores of epithelial injury. In both models, the levels of PGE2, TXB2 and LTB4 and tissue MPO were not significantly altered.
  
  
  CONCLUSIONS
  Although phenantroline did not modify the activity of inflammatory mediators, this compound substantially reduced intestinal injury associated with tissue remodelling.
authors.affiliation: Digestive Disease Research Unit, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Medina
authors.forename: S
authors.initials: S
authors.lastname: Videla
authors.forename: A
authors.initials: A
authors.lastname: Radomski
authors.forename: M
authors.initials: M
authors.lastname: Radomski
authors.forename: M
authors.initials: M
authors.lastname: Antolín
authors.forename: F
authors.initials: F
authors.lastname: Guarner
authors.forename: J
authors.initials: J
authors.lastname: Vilaseca
authors.forename: A
authors.initials: A
authors.lastname: Salas
authors.forename: J R
authors.initials: JR
authors.lastname: Malagelada
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D003106:Colon / Q000473:pathology; D016264:Dextran Sulfate; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D010618:Phenanthrolines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D014302:Trinitrobenzenesulfonic Acid; D015032:Zinc
chemical_list: D002614:Chelating Agents; D010618:Phenanthrolines; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate; D008666:Metalloendopeptidases; D015032:Zinc