Acute urinary retention and subsequent catheterization cause lipid peroxidation and oxidative DNA damage in the bladder: preventive effect of edaravone, a free‐radical scavenger

• Published in: BJU international Vol. 104; no. 5; pp. 713 - 717
• Main Authors: Shimizu, Shogo, Saito, Motoaki, Kinoshita, Yukako, Kazuyama, Emi, Tamamura, Mayuko, Satoh, Itaru, Satoh, Keisuke
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2009; Wiley-Blackwell
• Subjects: 8‐hydroxydeoxyguanosine; Acute Disease; acute urinary retention; Animals; Antipyrine - analogs & derivatives; Antipyrine - pharmacology; Biological and medical sciences; Cardiology. Vascular system; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - metabolism; DNA Damage - drug effects; edaravone; Free Radical Scavengers - pharmacology; HSP70 Heat-Shock Proteins - metabolism; HSP‐70; ischaemia‐reperfusion; Lipid Peroxidation - drug effects; Male; malondialdehyde; Malondialdehyde - metabolism; Medical sciences; Nephrology. Urinary tract diseases; Oxidative Stress - drug effects; Random Allocation; Rats; Rats, Sprague-Dawley; Urinary Bladder Diseases - metabolism; Urinary Bladder Diseases - prevention & control; Urinary Catheterization; Urinary Retention - prevention & control; Urinary system involvement in other diseases. Miscellaneous; Urinary tract. Prostate gland; Oxidative stress; Nephrology; Lipids; Free radical; Urology; Prevention; Voiding dysfunction; HSP-70; Urinary bladder; 8-hydroxydeoxyguanosine; acute urinary retention; Heat shock protein 70; Edaravone; malondialdehyde; Peroxidation; Urinary system disease; Catheterization; edaravon; Acute; Ischemia reperfusion; Urinary retention; ischaemia-reperfusion; Antioxidant; Radical scavenger; Urinary system; Lesion
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1111/j.1464-410X.2009.08471.x

OBJECTIVE To investigate the effect of a free‐radical scavenger, edaravone, on the changes occurring with acute urinary retention (AUR) and subsequent catheterization in the rat bladder. MATERIALS AND METHODS Eight‐week‐old male Sprague Dawley rats were allocated to one of four groups; an AUR group that had urinary retention induced, with subsequent catheterization; two edaravone groups, given edaravone at 1 or 10 mg/kg body weight for 60 min and then the same urinary retention and subsequent catheterization; and a sham‐operated control group given edaravone 10 mg/kg. Urinary retention was induced by the clamping the rat penile urethra with a small clip, making a cystostomy, and then infusing 3 mL (0.6 mL/min) of saline with an infusion pump. The obstruction was sustained for 30 min and then the bladder was allowed to drain with a catheter in place for 60 min as the studies continued. After killing the rats the function of the bladder was assessed, with carbachol and 100 mm KCl, and the levels of malondialdehyde (MDA, a marker of lipid peroxidation), 8‐hydroxydeoxyguanosine (8‐OHdG; a marker of oxidative DNA damage), heat‐shock protein 70 (HSP 70) and its mRNA were measured. RESULTS AUR increased the intravesical pressure and decreased blood flow, and subsequent catheterization decreased the intravesical pressure and increased blood flow. Edaravone induced a decrease in blood flow in the bladder during the urinary retention and subsequent catheterization compared to the blood flow in the AUR group. Edaravone resulted in protection of the contractile responses to both carbachol and KCl in a dose‐dependent manner. The MDA concentration, 8‐OHdG content and expressions of HSP‐70 and its mRNA in the AUR group were significantly larger than those of the control group. Edaravone markedly suppressed the accumulations of MDA and 8‐OHdG in the bladder, and reduced the expressions of HSP 70 and its mRNA. CONCLUSION These results indicate that edaravone reduces the oxidative stress and prevents the bladder dysfunction caused by AUR and subsequent catheterization.