Preventive Effect of Hydrogen Water on the Development of Detrusor Overactivity in a Rat Model of Bladder Outlet Obstruction.

PURPOSE: Bladder ischemia and oxidative stress contribute to the pathogenesis of bladder dysfunction caused by bladder outlet obstruction. H2 reportedly acts as an effective antioxidant. We investigated whether oral ingestion of H2 water would have a beneficial effect on bladder function in a rat model of bladder outlet obstruction. MATERIALS AND METHODS: H2 water was made by dissolving H2 gas in ordinary drinking water using a hydrogen water producing apparatus. The bladder outlet obstruction model was surgically induced in male rats. Rats with obstruction were fed H2 water or ordinary drinking water. On week 4 postoperatively cystometry was performed. Oxidative stress markers and the bladder nerve growth factor level were determined. Bladder tissues were processed for pharmacological studies and histological analysis. RESULTS: The micturition interval and micturition volume significantly decreased in obstructed rats given ordinary drinking water. These decreases were significantly suppressed by oral ingestion of H2 water. Increased post-void residual volume in obstructed rats was significantly reduced by H2 water. Obstruction led to a significant increase in bladder weight, oxidative stress markers and nerve growth factor. H2 water significantly suppressed these increases without affecting bladder weight. There was no significant difference in histological findings between rats with bladder obstruction given H2 water and ordinary drinking water. Decreased responses of detrusor muscle strips from obstructed bladders to KCl, carbachol and electrical field stimulation were reversed by H2 water ingestion. CONCLUSIONS: Results suggest that H2 water could ameliorate bladder dysfunction secondary to bladder outlet obstruction by attenuating oxidative stress.

Effect of melatonin on chronic bladder-ischaemia-associated changes in rat bladder function.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: There are many studies showing melatonin's potent endogenous free radical scavenging and antioxidative properties, which protect against oxidative insult, but there is no information about the effect of chronic treatment with melatonin on oxidative-stress-related bladder dysfunction caused by chronic ischaemia. The model used in this study shows that functional and morphological changes caused by chronic bladder ischaemia and oxidative stress were protected by chronic treatment with melatonin, resulting in improvement of bladder hyperactivity. OBJECTIVE: To investigate the potential therapeutic benefit of melatonin for chronic ischaemia-related bladder dysfunction. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were divided into control, arterial injury (AI), AI with low-dose melatonin treatment (AI-ML) and AI with high-dose melatonin treatment (AI-MH) groups. The AI, AI-ML and AI-MH groups underwent a procedure to induce endothelial injury of the iliac arteries and received a 2% cholesterol diet after AI. The rats in the AI-ML and AI-MH groups were treated with melatonin 2.5 or 20 mg/kg/day orally for 8 weeks after AI. The control group received a regular diet. After 8 weeks, urodynamic investigations were performed. Bladder tissues and iliac arteries were processed for pharmacological studies, and for immunohistochemical and histological examination. RESULTS: Iliac arteries from AI, AI-ML and AI-MH rats displayed neo-intimal formation and luminal occlusion. In the AI group, the micturition interval was significantly shorter, and bladder capacity and voided volume were lower than in the controls. Contractile responses of bladder strips to KCl, electrical field stimulation and carbachol were significantly lower after AI than in the controls. The AI bladders were found to have a significantly increased collagen ratio, oxidative stress and inducible nitric oxide synthase (NOS) expression, and decreased constitutive NOS expression compared with the controls. In the AI-ML and AI-MH groups, neo-intimal formation was not prevented, but there were beneficial effects on bladder function and morphology. In the AI-ML group, the beneficial effects failed to reach statistical significance. In the AI-MH group, melatonin significantly improved oxidative stress and NOS expression, and there were significant improvements in all the functional and morphological variables compared with the AI group. CONCLUSIONS: Arterial occlusive disease may lead to chronic bladder ischaemia and bladder hyperactivity associated with oxidative stress. In the model used, chronic treatment with melatonin protected bladder function and morphology, probably through its free radical scavenging and antioxidative properties. Melatonin may prevent oxidative damage and improve ischaemia-related bladder dysfunction.

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.