title: Suppression of bladder overactivity and oxidative stress by the phytotherapeutic agent, Eviprostat, in a rat model of atherosclerosis-induced chronic bladder ischemia.
abstract: OBJECTIVE
  To clarify the mechanism by which chronic bladder ischemia causes bladder functional changes, and to investigate the involvement of oxidative stress and pro-inflammatory cytokines, and the effects of the phytotherapeutic drug, Eviprostat, on these biochemical marker levels and bladder function.
  
  
  METHODS
  Male Sprague-Dawley rats aged 15 weeks were divided into three groups. Arterial injury was experimentally induced by balloon endothelial injury of the iliac arteries, and a 2% cholesterol diet was given for 8 weeks. Rats in the arterial-injury group were given daily oral vehicle or Eviprostat, whereas sham-operated animals on a regular diet (0.09% cholesterol) were given vehicle for the last 2 weeks. Eight weeks after surgery, the levels of bladder pro-inflammatory cytokines, as well as bladder and urinary oxidative-stress markers, were determined. Cystometrograms were carried out without anesthesia or restraint.
  
  
  RESULTS
  Bladder and urinary oxidative-stress markers, and bladder pro-inflammatory cytokine levels were significantly increased in the arterial-injury group, and Eviprostat markedly suppressed these increase. The cystometrograms showed that arterial injury decreased the intermicturition interval without affecting the micturition pressure. This decrease was reversed by Eviprostat treatment.
  
  
  CONCLUSIONS
  Oxidative stress and pro-inflammatory cytokines might be involved in the development of overactive bladder by atherosclerosis-induced chronic bladder ischemia. Eviprostat might provide an attractive treatment option for individuals with bladder dysfunction due to chronic bladder ischemia because of its anti-oxidant and anti-inflammatory properties.
authors.affiliation: Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan. m.oka@po.nippon-shinyaku.co.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Matsui
authors.forename: Michiko
authors.initials: M
authors.lastname: Oka
authors.forename: Tomomi
authors.initials: T
authors.lastname: Fukui
authors.forename: Mitsushi
authors.initials: M
authors.lastname: Tanaka
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Oyama
authors.forename: Koji
authors.initials: K
authors.lastname: Sagawa
authors.forename: Masanori
authors.initials: M
authors.lastname: Nomiya
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamaguchi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D050197:Atherosclerosis / Q000150:complications; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004338:Drug Combinations; D004979:Ethamsylate / Q000494:pharmacology* / Q000627:therapeutic use*; D016209:Interleukin-8 / Q000378:metabolism; D007511:Ischemia / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D023421:Models, Animal; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001743:Urinary Bladder / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000378:metabolism; D014554:Urination / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects
chemical_list: D004338:Drug Combinations; D016209:Interleukin-8; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D004979:Ethamsylate; D008315:Malondialdehyde; C010152:eviprostat; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine