Mp28-08 Oxidative Stress Accelerates the Transition From Compensated to Decompensated Bladder Function in STZ-Induced Diabetic Mice

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology I1 Apr 2016MP28-08 OXIDATIVE STRESS ACCELERATES THE TRANSITION FROM COMPENSATED TO DECOMPENSATED BLADDER FUNCTION IN STZ-INDUCED DIABETIC MICE Rania Elrashidy, Guiming Liu, Michael Kavran, Mervat Asker, Sousou Ali, Hoda Mohamed, and Firouz Daneshgari Rania ElrashidyRania Elrashidy More articles by this author , Guiming LiuGuiming Liu More articles by this author , Michael KavranMichael Kavran More articles by this author , Mervat AskerMervat Asker More articles by this author , Sousou AliSousou Ali More articles by this author , Hoda MohamedHoda Mohamed More articles by this author , and Firouz DaneshgariFirouz Daneshgari More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1058AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Diabetes affects bladder function significantly. We have shown that diabetic bladder undergoes a transition from compensated to decompensated phase. However, the mechanisms of the transition are not clear. In this study we test the hypothesis that oxidative stress plays a key role in this transition using our recently created smooth muscle (SM)-specific Sod2 knockout (KO) mouse model. METHODS 8-week-old male Sod2lox/lox, SM-CreERT2(ki)Cre/+ mice or wild type mice were treated with 4 hydroxy tamoxifen (OHT) to induce Cre-mediated excision of floxed Sod2 allele. Two weeks after OHT injection, Sod2lox/lox, SM-CreERT2(ki)Cre/+ mice and wild type mice were randomly assigned to diabetic or control groups. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) while control mice were injected with vehicle. Nine weeks later, half of mice in each group were used to evaluate bladder functions by conscious cystometry, whereas bladders were harvested from the other half for immunoblotting analysis. RESULTS Both wild type diabetic and SM-specific Sod2 KO diabetic mice showed hyperglycemia, less body weight and increased bladders weights compared with their corresponding control groups. Induction of diabetes in wild type mice resulted in significant increases in nitrotyrosine levels, along with a compensatory increase in MnSOD expression in detrusor tissue. Induction of diabetes in SM-specific Sod2 KO mice causes even more increases in nitrotyrosine levels, compared with wild type diabetic mice. Conscious cystometry revealed higher peak voiding pressure (PVP), increased voiding volume, bladder capacity and compliance in wild type diabetic mice compared with wild type control mice. Whereas, Sod2 KO diabetic mice revealed a marked drop in the PVP, increased post-void residual volume and decreased voiding volume compared with wild type diabetic mice, suggesting voiding dysfunction. This was associated with significant increases in the expressions of BAX and activated caspase-3 as pro-apoptotic markers, along with a significant reduction in Bcl-2, as an anti-apoptotic marker in detrusor tissues of both diabetic groups, compared with their respective controls, with more pronounced effects in Sod2 KO diabetic mice than wild type diabetic mice. CONCLUSIONS Our findings showed that increased oxidative stress can accelerate the transition from compensated to decompensated phase in diabetic mice, likely through activation of apoptotic pathways. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e373-e374 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Rania Elrashidy More articles by this author Guiming Liu More articles by this author Michael Kavran More articles by this author Mervat Asker More articles by this author Sousou Ali More articles by this author Hoda Mohamed More articles by this author Firouz Daneshgari More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...