Effect of eviprostat on bladder overactivity in an experimental cystitis rat model.
OBJECTIVE
The purpose of this study was to investigate the effects of eviprostat, a phytotherapeutic drug, on bladder overactivity and inflammation in a cyclophosphamide (CYP)-induced cystitis rat model.


METHODS
Female Sprague-Dawley rats received a single intraperitoneal injection of CYP (200 mg/kg) or saline. After the CYP injection, eviprostat (9, 18 or 54 mg/kg per day) or a vehicle was orally given twice each day. Four days after the CYP injection, bladder function was evaluated by cystometrograms under urethane anesthesia. In a separate group, bladder inflammation was compared between the eviprostat- or vehicle-treated animals. Furthermore, the effects of eviprostat on carbachol-induced muscle contraction were evaluated by an in vitro experiment.


RESULTS
The intercontraction interval (ICI) significantly decreased in the CYP-injected rats in comparison to the saline-injected rats. In the CYP-injected group, 18 and 54 mg/kg per day of eviprostat treatment significantly increased the ICI, but did not change the maximum voiding pressure in comparison to the vehicle treatment. In the saline-injected group, no significant changes of any parameters in the cystometrograms were observed between the eviprostat- and vehicle-treated groups. CYP-induced bladder inflammation tended to be lower in the eviprostat-treated group in comparison to the vehicle-treated group. An in vitro experiment revealed that eviprostat failed to inhibit carbachol-induced muscle contraction.


CONCLUSIONS
The oral administration of eviprostat suppressed CYP-induced bladder overactivity. The effects of eviprostat on the micturition reflex may be irrespective of antimuscarinic action. The present findings raise the possibility that eviprostat could be an effective treatment for bladder overactivity associated with inflammation.
Kobayashi
Mizuki
M
Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Nomura
Masayoshi
M
Nishii
Hisae
H
Matsumoto
Seiji
S
Fujimoto
Naohiro
N
Matsumoto
Tetsuro
T
D000818:Animals; D018906:Antineoplastic Agents, Alkylating; D002217:Carbachol; D018679:Cholinergic Agonists; D003520:Cyclophosphamide; D003556:Cystitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004338:Drug Combinations; D004979:Ethamsylate / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D009119:Muscle Contraction / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology; D053201:Urinary Bladder, Overactive / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D014554:Urination / Q000187:drug effects*
D018906:Antineoplastic Agents, Alkylating; D018679:Cholinergic Agonists; D004338:Drug Combinations; D010936:Plant Extracts; D004979:Ethamsylate; C010152:eviprostat; D003520:Cyclophosphamide; D002217:Carbachol