title: Effect of the phytotherapeutic agent eviprostat on the bladder in a rat model of bladder overdistension/emptying.
abstract: OBJECTIVE
  Ischemia-reperfusion injury is an important factor in the development of lower urinary tract symptoms (LUTS) that is partly mediated by the generation of free radicals. We investigate the effect of the phytotherapeutic agent Eviprostat, a treatment for benign prostatic hyperplasia (BPH) that has antioxidant and anti-inflammatory activity, on urinary bladder blood flow (BBF), and function in a rat model of bladder overdistension and emptying (OE).
  
  
  METHODS
  For 8 days before surgery, OE rats received daily oral Eviprostat (36 mg/kg/day) or vehicle, while sham-operated animals received vehicle. The bladder was distended by infusion of saline over a period of 2 hr (overdistension) and then emptied. After 24 hr, BBF was measured with a laser speckle blood flow imager. The oxidative-stress marker malondialdehyde (MDA), proinflammatory cytokines, and myeloperoxidase were determined in the isolated bladder, and histological analysis was performed. Functional contractile responses of bladder strips to electrical field stimulation, carbachol, and KCl were measured.
  
  
  RESULTS
  Twenty-four hours after bladder OE, a significant decrease in BBF and significant increases in bladder weight, malondialdehyde, proinflammatory cytokines, and myeloperoxidase were observed. Eviprostat almost completely prevented these changes. Histological analysis of the bladder of OE rats showed hemorrhage, accumulation of leukocytes, desquamation of epithelium, and edema, and Eviprostat suppressed these changes. The reduction in functional contractile forces in the bladder of OE rats was also prevented by Eviprostat.
  
  
  CONCLUSIONS
  Eviprostat-mediated suppression of increased bladder oxidative stress and inflammation caused by bladder OE may contribute to the improvement of BBF and bladder function by Eviprostat.
authors.affiliation: Discovery Research Laboratories, Nippon Shinyaku Co., Ltd., Nishinosho-monguchi-cho, Kisshoin, Minami-ku, Kyoto, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kawai
authors.forename: Michiko
authors.initials: M
authors.lastname: Oka
authors.forename: Junko
authors.initials: J
authors.lastname: Kyotani
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Oyama
authors.forename: Seiji
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Kakizaki
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001783:Blood Flow Velocity; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004338:Drug Combinations; D004979:Ethamsylate / Q000494:pharmacology*; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D017078:Laser-Doppler Flowmetry; D008315:Malondialdehyde / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D013997:Time Factors; D001743:Urinary Bladder / Q000098:blood supply / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001748:Urinary Bladder Neck Obstruction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D004338:Drug Combinations; D018836:Inflammation Mediators; D010936:Plant Extracts; D004979:Ethamsylate; D008315:Malondialdehyde; C010152:eviprostat; D009195:Peroxidase
keywords: Eviprostat; benign prostatic hyperplasia; bladder blood flow; bladder function; oxidative stress; proinflammatory cytokines