title: High-dose tranilast administration to rats creates interstitial cystitis-like symptoms with increased vascular permeability.
abstract: OBJECTIVE
  We investigated whether the high-dose administration of tranilast could be used to create an animal model of interstitial cystitis (IC). Then, we used this model to assess the relationship between IC and changes in the vascular permeability of the bladder.
  
  
  METHODS
  Female rats were divided into the following 4 groups: a control group, a tranilast group, a carbazochrome group and a combination (tranilast+carbazochrome) group. Continuous cystometry, bladder distension, and the Evans blue dye extravasation test were performed 4weeks after drug administration. Locomotor activity, the plasma TGF-β1 level, and collagen fibers in the bladder wall were also examined in the control and tranilast groups.
  
  
  RESULTS
  The interval between bladder contractions was shorter and the leakage of Evans blue dye into the bladder wall was greater in the tranilast group than in the control group. Glomerulations of the bladder wall after bladder distention and thinning of the collagen fiber layer in the bladder were observed in the tranilast group. Locomotor activity in darkness and the plasma TGF-β1 level were both lower in the tranilast group than in the control group. In the combination group, the leakage of Evans blue dye was greater than in the control group; however, it was less prominent than in the tranilast group.
  
  
  CONCLUSIONS
  These results suggest that high-dose administration of tranilast to rats can create an IC-like rat model and that an increase in the vascular permeability of the bladder wall may be one cause of IC symptoms.
authors.affiliation: Southern Knights' Laboratory LLP, Okinawa, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Nishijima
authors.forename: Kimio
authors.initials: K
authors.lastname: Sugaya
authors.forename: Katsumi
authors.initials: K
authors.lastname: Kadekawa
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Ashitomi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ueda
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamamoto
mesh_terms: D000323:Adrenochrome / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000633:toxicity; D002199:Capillary Permeability / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism; D018856:Cystitis, Interstitial / Q000139:chemically induced / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D009043:Motor Activity / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000097:blood; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology*; D062367:ortho-Aminobenzoates / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D018926:Anti-Allergic Agents; D053773:Transforming Growth Factor beta1; D062367:ortho-Aminobenzoates; D000323:Adrenochrome; C073338:carbazochrome; D003094:Collagen; C012293:tranilast
keywords: Interstitial cystitis; Tranilast; Vascular permeability