PURPOSE: The present study aimed to characterize pharmacological effects of a phytotherapeutic agent, Eviprostat® (EVI), on urodynamic parameters, bladder muscarinic and purinergic receptors and urinary cytokines in rats with cystitis induced by cyclophosphamide (CYP).
MATERIALS AND METHODS: The urodynamic parameters in CYP (150 mg/kg i.p.)-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 chloride ([(3)H]NMS) and αβ -methylene-ATP [2,8-(3)H] tetrasodium salt ([(3)H] αβ-MeATP), respectively. Urinary cytokines (interleukin-1β [IL-1β], IL-6 and IL-17) were measured with ELISA kits. EVI (36 mg/kg/day, twice a day, 7 days) was orally administered.
RESULTS: In the cystometry of CYP-treated rats compared with sham rats, micturition interval and micturition volume were significantly decreased, and the frequency of micturition, basal pressure and residual urine volume were significantly increased. Repeated oral administration of EVI in CYP-treated rats significantly increased micturition interval and micturition volume and decreased the frequency of micturition, basal pressure and residual urine volume. The maximal number of binding sites (Bmax) for [(3)H]NMS and [(3)H] αβ-MeATP was significantly decreased in the bladder of CYP-treated rats compared with sham rats. Such decreases were significantly attenuated by the repeated treatment with EVI. The elevation in urinary cytokine levels in CYP-treated rats was also effectively attenuated by the EVI treatment.
CONCLUSION: Repeated treatment with EVI improved significantly detrusor overactivity, down-regulated expression of bladder pharmacological receptors and elevated urinary cytokine levels in rats with CYP-induced cystitis. Therefore, EVI may be a pharmacologically useful phytotherapeutic agent for cystitis.
Written by:
Nasrin S, Masuda E, Kugaya H, Ito Y, Yamada S. Are you the author?
Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
Reference: J Urol. 2012 Sep 20. pii: S0022-5347(12)04908-7.
doi: 10.1016/j.juro.2012.09.054
PubMed Abstract
PMID: 23000860
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