title: Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis.
abstract: BACKGROUND
  Reactive oxygen species may mediate tissue injury in inflammatory bowel disease. Aminosalicylates have antioxidant activity and the antioxidants, superoxide dismutase and allopurinol, are of reported benefit in inflammatory bowel disease.
  
  
  OBJECTIVE
  To develop a convenient technique for testing the antioxidant potential of standard and novel therapeutic agents for use in inflammatory bowel disease.
  
  
  METHODS
  Amplified chemiluminescence was used to measure reactive oxygen species production by colonic biopsy specimens from rats with acetic acid induced colitis and to assess the in vitro effect of conventional antioxidants, standard therapies and proposed novel therapies for inflammatory bowel disease.
  
  
  RESULTS
  The model was validated by demonstrating that the profile of effects on chemiluminescence of acetic acid induced colitis biopsy specimens given by conventional antioxidants (sodium azide, catalase, copper-zinc superoxide dismutase, dimethyl sulphoxide, N-acetylcysteine and ascorbate) and standard therapies (5-aminosalicylate and hydrocortisone) resembled that previously reported using biopsy specimens from ulcerative colitis. Human recombinant manganese superoxide dismutase did not alter chemiluminescence. Two novel compounds, LY231617 (10 mM) and amflutizole (20 mM), reduced chemiluminescence by 98% (n = 5, p = 0.009) and 88% (n = 5, p = 0.03), respectively.
  
  
  CONCLUSIONS
  The similarity of the chemiluminescence responses of colonic biopsy specimens from acetic acid induced colitis and ulcerative colitis to a range of conventional antioxidants and standard treatments suggests that this model is a useful method for testing the antioxidant potential of new therapies for inflammatory bowel disease. The antioxidant actions of dimethyl sulphoxide, ascorbate, and the novel compounds, amflutizole and LY231617 in this model suggest that these agents merit further assessment in the treatment of inflammatory bowel disease.
authors.affiliation: Gastrointestinal Science Unit, London Hospital Medical College.
authors.forename: A D
authors.initials: AD
authors.lastname: Millar
authors.forename: D S
authors.initials: DS
authors.lastname: Rampton
authors.forename: C L
authors.initials: CL
authors.lastname: Chander
authors.forename: A W
authors.initials: AW
authors.lastname: Claxson
authors.forename: S
authors.initials: S
authors.lastname: Blades
authors.forename: A
authors.initials: A
authors.lastname: Coumbe
authors.forename: J
authors.initials: J
authors.lastname: Panetta
authors.forename: C J
authors.initials: CJ
authors.lastname: Morris
authors.forename: D R
authors.initials: DR
authors.lastname: Blake
mesh_terms: D019342:Acetic Acid; D000636:Aminosalicylic Acids / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002084:Butylated Hydroxytoluene / Q000031:analogs & derivatives / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000473:pathology*; D003093:Colitis, Ulcerative / Q000188:drug therapy; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D046508:Culture Techniques; D004195:Disease Models, Animal; D006854:Hydrocortisone / Q000494:pharmacology; D008163:Luminescent Measurements; D008297:Male; D019804:Mesalamine; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D000636:Aminosalicylic Acids; D000975:Antioxidants; D017382:Reactive Oxygen Species; D013844:Thiazoles; D002084:Butylated Hydroxytoluene; D019804:Mesalamine; C046749:amflutizole; C081064:LY 231617; D019342:Acetic Acid; D006854:Hydrocortisone