title: Improvement by phytotherapeutic agent of detrusor overactivity, down-regulation of pharmacological receptors and urinary cytokines in rats with cyclophosphamide induced cystitis.
abstract: OBJECTIVE
  We characterized pharmacological effects of the phytotherapeutic agent Eviprostat® on urodynamic parameters, bladder muscarinic and purinergic receptors, and urinary cytokines in rats with cyclophosphamide induced cystitis.
  
  
  METHODS
  Urodynamic parameters in cyclophosphamide (150 mg/kg intraperitoneally) treated rats were measured by a cystometric method. Muscarinic and purinergic receptors in the bladder and other tissues were measured by radioreceptor assays using [N-methyl-(3)H]scopolamine methyl chloride and [(3)H]αβ-MeATP, respectively. The urinary cytokines interleukin-1β, 6 and 17 were measured with enzyme-linked immunoassay kits. Eviprostat (36 mg/kg per day twice daily for 7 days) was orally administered.
  
  
  RESULTS
  On cystometry the micturition interval and micturition volume were significantly decreased in cyclophosphamide vs sham treated rats, while micturition frequency, basal pressure and post-void residual urine volume were significantly increased. Repeat oral administration of Eviprostat in cyclophosphamide treated rats significantly increased the micturition interval and micturition volume, and decreased micturition frequency, basal pressure and post-void residual urine volume. The maximal number of binding sites for [N-methyl-(3)H]scopolamine methyl chloride and [(3)H]αβ-MeATP was significantly decreased in the bladder of cyclophosphamide vs sham treated rats. Such decreases were significantly attenuated by repeat Eviprostat treatment. Increased urinary cytokine levels in cyclophosphamide treated rats were also effectively attenuated by Eviprostat.
  
  
  CONCLUSIONS
  Repeat Eviprostat treatment significantly improved detrusor overactivity, down-regulated the expression of bladder pharmacological receptors and increased urinary cytokine levels in rats with cyclophosphamide induced cystitis. Therefore, Eviprostat may be a pharmacologically useful phytotherapeutic agent for cystitis.
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Sweety
authors.initials: S
authors.lastname: Nasrin
authors.forename: Eiji
authors.initials: E
authors.lastname: Masuda
authors.forename: Haruna
authors.initials: H
authors.lastname: Kugaya
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Ito
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
mesh_terms: D000818:Animals; D003520:Cyclophosphamide / Q000633:toxicity; D003556:Cystitis / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D016207:Cytokines / Q000652:urine*; D015536:Down-Regulation / Q000187:drug effects*; D004338:Drug Combinations; D004979:Ethamsylate / Q000494:pharmacology*; D005260:Female; D008517:Phytotherapy / Q000379:methods; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011983:Receptors, Purinergic / Q000187:drug effects / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D014563:Urodynamics / Q000187:drug effects
chemical_list: D016207:Cytokines; D004338:Drug Combinations; D010936:Plant Extracts; D011983:Receptors, Purinergic; D004979:Ethamsylate; C010152:eviprostat; D003520:Cyclophosphamide