Effect of the phytotherapeutic agent eviprostat on the bladder in a rat model of bladder overdistension/emptying.

AIMS: 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. CONCLUSION: 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.

Effect of tramadol on pain-related behaviors and bladder overactivity in rodent cystitis models.

Tramadol is a widely used analgesic that stimulates the µ opioid receptor and inhibits serotonin and noradrenalin reuptake. There have been studies on the analgesic effects of tramadol based on the tail-flick test, the formalin test, and the induction of allodynia by sciatic-nerve ligation. However, the effects of tramadol on behaviors related to bladder pain and bladder overactivity induced by cystitis have not been reported. To investigate the usefulness of tramadol for patients with cystitis, we investigated these effects of tramadol in rodent cystitis models. Intraperitoneal injection of cyclophosphamide caused bladder-specific inflammation and increases in pain-related behaviors, the number of voids and bladder weight in mice. Tramadol suppressed the cyclophosphamide-induced pain-related behaviors but did not affect the number of voids or the bladder weight. During continuous-infusion cystometrograms in anesthetized rats, cyclophosphamide shortened the intercontraction interval, indicating bladder overactivity. Tramadol significantly prolonged the intercontraction interval, and the effect was partially blocked by the opioid antagonist naloxone. This finding indicates that µ opioid receptors may be involved in the action of tramadol. In conclusion, tramadol ameliorated cyclophosphamide-induced bladder-pain-related behaviors and bladder overactivity in rodents. These findings suggest that tramadol might be a treatment option for cystitis-induced bladder pain and bladder overactivity.

Effect of the phytotherapeutic agent Eviprostat on 17beta-estradiol-induced nonbacterial inflammation in the rat prostate.

BACKGROUND: Anti-inflammatory medications have been used for the treatment of chronic prostatitis. The phytotherapeutic agent Eviprostat, a popular treatment for benign prostatic hyperplasia in Japan and Germany, has antioxidant and anti-inflammatory activity. We investigated the effects of the phytotherapeutic agent Eviprostat on prostate inflammation induced in castrated rats by the injection of 17beta-estradiol. METHODS: Ten-month-old male Wistar rats were divided into five groups. Nonbacterial prostatitis was experimentally induced in groups 2-5 by castration followed by daily subcutaneous injection of 17beta-estradiol for 30 days. The rats were orally administered 0.1% Tween-80 (group 2), low-dose Eviprostat (group 3), high-dose Eviprostat (group 4), or cernitin pollen extract (group 5) for the last 2 weeks of 17beta-estradiol administration. Sham-operated rats (group 1) were orally administered 0.1% Tween-80. On the 31st day after surgery, the weight of the prostate and the levels of prostatic proinflammatory cytokines as well as the oxidative-stress marker malondialdehyde were determined and histological alterations noted. RESULTS: Experimentally induced nonbacterial prostatitis led to a significant decrease in prostate weight and increases in malondialdehyde and proinflammatory cytokine levels. Eviprostat significantly suppressed the increases in malondialdehyde and cytokine levels without affecting prostate weight. Histologically, nonbacterial prostatitis was evident in the lateral lobe of the prostate, and Eviprostat treatment significantly suppressed the severity of the lesion. CONCLUSIONS: Eviprostat, which has effective antioxidant and anti-inflammatory activities in the prostate, may be useful for the clinical treatment of chronic prostatitis. These activities of Eviprostat may also contribute to the amelioration of prostate inflammation in BPH patients. Prostate 69: 1404-1410, 2009. (c) 2009 Wiley-Liss, Inc.