Suppression of bladder overactivity and oxidative stress by the phytotherapeutic agent, Eviprostat, in a rat model of atherosclerosis-induced chronic bladder ischemia.

OBJECTIVES: To clarify the mechanism by which chronic bladder ischemia causes bladder functional changes, and to investigate the involvement of oxidative stress and pro-inflammatory cytokines, and the effects of the phytotherapeutic drug, Eviprostat, on these biochemical marker levels and bladder function. METHODS: Male Sprague-Dawley rats aged 15 weeks were divided into three groups. Arterial injury was experimentally induced by balloon endothelial injury of the iliac arteries, and a 2% cholesterol diet was given for 8 weeks. Rats in the arterial-injury group were given daily oral vehicle or Eviprostat, whereas sham-operated animals on a regular diet (0.09% cholesterol) were given vehicle for the last 2 weeks. Eight weeks after surgery, the levels of bladder pro-inflammatory cytokines, as well as bladder and urinary oxidative-stress markers, were determined. Cystometrograms were carried out without anesthesia or restraint. RESULTS: Bladder and urinary oxidative-stress markers, and bladder pro-inflammatory cytokine levels were significantly increased in the arterial-injury group, and Eviprostat markedly suppressed these increase. The cystometrograms showed that arterial injury decreased the intermicturition interval without affecting the micturition pressure. This decrease was reversed by Eviprostat treatment. CONCLUSIONS: Oxidative stress and pro-inflammatory cytokines might be involved in the development of overactive bladder by atherosclerosis-induced chronic bladder ischemia. Eviprostat might provide an attractive treatment option for individuals with bladder dysfunction due to chronic bladder ischemia because of its anti-oxidant and anti-inflammatory properties.

Eviprostat suppresses urinary oxidative stress in a rabbit model of partial bladder outlet obstruction and in patients with benign prostatic hyperplasia.

Eviprostat is a phytotherapeutic agent that has been used widely for more than 40 years in the treatment of benign prostatic hyperplasia (BPH) in Japan and Germany, and is known to have antioxidant activity. The present study investigated the effect of Eviprostat on the levels of the urinary oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) in a rabbit model of surgical partial bladder outlet obstruction (PBOO) and in patients with lower urinary tract symptoms (LUTS) associated with BPH. In the rabbit model, 8-OHdG levels in urine collected after 3 weeks of PBOO were 3.8-fold higher than in the urine of sham-operated rabbits. When twice-daily Eviprostat was administered orally throughout the 3-week PBOO period, the increase in urinary 8-OHdG levels was suppressed by 70%. In the clinical study, nine patients who received Eviprostat for 4 weeks showed 2.5-fold lower urinary 8-OHdG levels than before treatment. During Eviprostat treatment, the total International Prostate Symptom Score (IPSS) decreased from 16.56 +/- 2.74 to 13.67 +/- 2.30 and the quality of life score from 4.22 +/- 0.40 to 3.22 +/- 0.46. The findings provide evidence that the antioxidant activity of Eviprostat is responsible for its beneficial effects in the treatment of BPH.