You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research II1 Apr 2012118 ONOBOTULINUMTOXIN A AMELIORATES OXIDATIVE STRESS-INDUCED DETRUSOR OVERACTIVITY Alex Lin, C.C. Lin, Y.Z. Shu, and K.K. Chen Alex LinAlex Lin Taipei, Taiwan More articles by this author , C.C. LinC.C. Lin Taipei, Taiwan More articles by this author , Y.Z. ShuY.Z. Shu Taipei, Taiwan More articles by this author , and K.K. ChenK.K. Chen Taipei, Taiwan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.166AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We investigated the effect of onobotulinumtoxin A on the detrusor overactivity resulting from H2O2-induced oxidative stress. METHODS The urinary bladders of male New Zealand rabbit were treated with intravesical protamine sulfate followed by instillation of either 50 units onobotulinumtoxin A (BTX-H2O2 group, n=6) or normal saline (NS- H2O2 group, n=6) for one hour. One week later continuous cystometry with 1% hydrogen peroxide (H2O2) or normal saline (NS-NS, n=6) was performed for one hour. Contractile responses to 120mM KCl, field stimulation and bethanechol were then tested on bladder strips with (Uro+) and without (Uro−) urothelial layer in organ bath. Separate groups of animals received subcutaneous capsaicin (n=3) 4 days before or intravenous indomethacin (n=3) during intravesical H2O2 infusion. Expression of nitrotyrosine was determined with immunohistochemistry. RESULTS Comparing with NS-NS group, intravesical H2O2(NS-H2O2) induced detrusor overactivity with a significant reduction in the cystometric bladder capacity and inter-contraction interval. Prior treatment with intravesical onobotulinumtoxin A abolished the stimulatory effects of H2O2. Pre-treatment with subcutaneous capsaicin or intravenous indomethacin during H2O2 infusion also abolished the stimulation of H2O2 on bladder activity. The contractile response of detrusor strips of NS- H2O2 group to KCl, field stimulation and bethanechol was significantly higher than that of strips obtained from NS-NS group. But the contractile response of strips obtained from BTX-H2O2 was similar to those of strips from NS-NS. The contractile response of Uro- strips was significantly greater than those of Uro+ strips in both NS-NS and BTX-H2O2 groups. However, in NS-H2O2 group the contractile response was not different between Uro+ and Uro- strips. Expression of nitrotyrosine was increased following H2O2 infusion, but there was no difference between BTX-H2O2 and NS-H2O2 groups. CONCLUSIONS H2O2-induced oxidative stress results in enhanced detrusor contractility and a loss of urothelial inhibitory activity on detrusor contraction. Capsaicin pre-treatment, intravenous indomethacin and pre-treatment with intravesical onobotulinumtoxin A ameliorate the stimulatory effect of H2O2 on bladder activity. We postulate that stimulatory effect of H2O2-induced oxidative stress on the bladder might be secondary to the enhanced prostaglandin synthesis mediating via c-fiber activation, which could be inhibited by onobotulinumtoxin A. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e48 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alex Lin Taipei, Taiwan More articles by this author C.C. Lin Taipei, Taiwan More articles by this author Y.Z. Shu Taipei, Taiwan More articles by this author K.K. Chen Taipei, Taiwan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...
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