title: Intravesical application of rebamipide suppresses bladder inflammation in a rat cystitis model.
abstract: OBJECTIVE
  We examined the effects of intravesical application of rebamipide (Otsuka Pharmaceutical, Tokyo, Japan) on bladder inflammation and overactivity in a chemically induced cystitis model.
  
  
  METHODS
  Female Sprague Dawley® rats under isoflurane anesthesia were injected with 150 mg/kg cyclophosphamide in the peritoneum, and 1 mM or 10 mM rebamipide or vehicle was administered in the bladder and remained for 1 hour. Control rats were injected with saline in the peritoneum and vehicle was administered in the bladder. The bladder was harvested at 48 hours. Hematoxylin and eosin staining was performed and the inflammation grade was assessed. The amount of myeloperoxidase was measured using enzyme-linked immunosorbent assay. Proinflammatory cytokines were quantified using reverse transcriptase-polymerase chain reaction. Cystometrogram was done in awake rats 48 hours after cyclophosphamide treatment to measure voiding reflex parameters.
  
  
  RESULTS
  Histological evaluation revealed that bladder inflammation in cyclophosphamide treated rats was suppressed by rebamipide in a dose dependent manner. Up-regulated myeloperoxidase, IL-1β, IL-6 and TNF-α expression in cyclophosphamide treated rats was also suppressed in rebamipide treated rats. Cystometrogram demonstrated that the intercontraction interval decreased in cyclophosphamide treated rats but was prolonged by rebamipide.
  
  
  CONCLUSIONS
  Intravesical application of rebamipide suppressed bladder inflammation and overactivity in a dose dependent manner. This may provide a new treatment strategy for chemotherapy associated cystitis.
authors.affiliation: Department of Urology, Nagoya University Graduate School of Medicine, Nagoya and National Center for Geriatrics and Gerontology (MY), Ohbu, Japan. Electronic address: yfunahashi@med.nagoya-u.ac.jp.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Funahashi
authors.affiliation: Department of Urology, Nagoya University Graduate School of Medicine, Nagoya and National Center for Geriatrics and Gerontology (MY), Ohbu, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Department of Urology, Nagoya University Graduate School of Medicine, Nagoya and National Center for Geriatrics and Gerontology (MY), Ohbu, Japan.
authors.forename: Tokunori
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Urology, Nagoya University Graduate School of Medicine, Nagoya and National Center for Geriatrics and Gerontology (MY), Ohbu, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Majima
authors.affiliation: Department of Urology, Nagoya University Graduate School of Medicine, Nagoya and National Center for Geriatrics and Gerontology (MY), Ohbu, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Takai
authors.affiliation: Department of Urology, Nagoya University Graduate School of Medicine, Nagoya and National Center for Geriatrics and Gerontology (MY), Ohbu, Japan.
authors.forename: Momokazu
authors.initials: M
authors.lastname: Gotoh
mesh_terms: D000283:Administration, Intravesical; D000409:Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D003556:Cystitis / Q000188:drug therapy*; D004195:Disease Models, Animal; D005260:Female; D015363:Quinolones / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015363:Quinolones; C052785:rebamipide; D000409:Alanine
keywords: cyclophosphamide; cystitis; inflammation; overactive; rebamipide; urinary bladder