title: Effects of FK506 on an experimental model of colitis in rats.
abstract: OBJECTIVE
  To assess the effects of FK506, a newly developed immunosuppressant, on experimental colitis in rats.
  
  
  METHODS
  Experimental colitis was induced by a single colonic instillation of hapten 2,4,6-trinitrobenzene sulphonic acid (TNB) in anaesthetized rats. Rats received 30 mg TNB dissolved in 0.25 mL of 50% ethanol, and were sacrificed on day 5 following 4 days dosing with FK506 (0.25, 0.5, 1.0, 2.0 mg/kg, s.c.) or vehicle. Mucosal prostanoid concentrations were determined using high performance liquid chromotography. Tissue myeloperoxidase activities were measured. The effects of FK506 on superoxide radical formation by neutrophils in both rats and humans were also estimated in vitro.
  
  
  RESULTS
  Administration of FK506 significantly reduced the colonic damage in a dose-dependent manner. Activities of myeloperoxidase and concentrations of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), PGF2 alpha and PGE2 in colonic tissue increased significantly following induction of experimental colitis, however, FK506 did not affect these changes. FK506 reduced stimulant-induced superoxide radical formation by neutrophils in rats and humans.
  
  
  CONCLUSIONS
  FK506 decreased superoxide radical generation by neutrophils, which might contribute to the lessening of colonic damage in this model.
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, University of Nagoya, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hoshino
authors.forename: H
authors.initials: H
authors.lastname: Goto
authors.forename: S
authors.initials: S
authors.lastname: Sugiyama
authors.forename: T
authors.initials: T
authors.lastname: Hayakawa
authors.forename: T
authors.initials: T
authors.lastname: Ozawa
mesh_terms: D000818:Animals; D003092:Colitis / Q000188:drug therapy* / Q000378:metabolism; D003106:Colon / Q000201:enzymology; D008297:Male; D009247:NADH, NADPH Oxidoreductases / Q000502:physiology; D019255:NADPH Oxidases; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D013481:Superoxides; D009195:Peroxidase; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D016559:Tacrolimus