RESUMEN
OBJECTIVES: To clarify the effect of saw palmetto extract (SPE), a phytotherapeutic agent, on urodynamic parameters, bladder muscarinic and purinergic receptors, and urinary cytokines in rats with cystitis induced by cyclophosphamide (CYP). METHODS: Saw palmetto extract (60 mg/kg per day) was administered orally twice a day for 7 days to rats. The urodynamic parameters in CYP (150 mg/kg i.p.)-treated rats were monitored by a cystometric method under anesthesia. The muscarinic and purinergic receptors in the bladder and submaxillary gland were measured by radioreceptor assays using [N-methyl-(3) H] scopolamine chloride([(3) H]NMS) and αß-methylene-ATP [2,8-(3) H] tetrasodium salt ([(3) H]αß-MeATP), respectively. Urinary cytokines (interleukin-1ß [IL-1ß], IL-6 and L-17) were measured with enzyme linked immunosorbent assay kits. RESULTS: Micturition interval and micturition volume were significantly decreased and the frequency of micturition and basal pressure were significantly increased in the CYP-treated rats compared with sham-operated rats. Orally administered SPE significantly increased the micturition interval and micturition volume and decreased the frequency of micturition and basal pressure. The maximal number of sites (Bmax ) for the specific binding of [(3) H]NMS and [(3) H]αß-MeATP was significantly decreased in the bladder. The decrease in receptors was attenuated by repeated treatment with SPE. An elevation in urinary cytokine (IL-1ß and IL-17) levels were seen, and this increase was effectively suppressed by SPE treatment. CONCLUSIONS: Saw palmetto extract attenuates the alteration of urodynamic parameters, pharmacologically relevant receptors, and urinary cytokines in CYP-treated rats. Therefore, SPE may be a potential therapeutic agent for improving the clinical symptoms of cystitis.
RESUMEN
PURPOSE: 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. MATERIALS AND 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]αß-MeATP, respectively. The urinary cytokines interleukin-1ß, 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]αß-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.