MP09-18 METFORMIN ATTENUATED THE INFLAMMATION AFTER BLADDER ISCHEMIA/REPERFUSION AND SUPPRESSED APOPTOSIS OF URINARY BLADDER IN RATS

Abstract

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology I1 Apr 2018MP09-18 METFORMIN ATTENUATED THE INFLAMMATION AFTER BLADDER ISCHEMIA/REPERFUSION AND SUPPRESSED APOPTOSIS OF URINARY BLADDER IN RATS Jong Mok Park, Ji Yong Lee, Seung Woo Yang, Ju Hyun Shin, Jae Sung Lim, Yong Gil Na, and Ki Hak Song Jong Mok ParkJong Mok Park More articles by this author , Ji Yong LeeJi Yong Lee More articles by this author , Seung Woo YangSeung Woo Yang More articles by this author , Ju Hyun ShinJu Hyun Shin More articles by this author , Jae Sung LimJae Sung Lim More articles by this author , Yong Gil NaYong Gil Na More articles by this author , and Ki Hak SongKi Hak Song More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.344AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Metformin is a first-line antidiabetic drug (Type 2 Diabetes Mellitus) with anti-hyperglycemic effects, and has the ability to decrease reactive oxygen species (ROS). Metformin also has a protective effect on the cardiovascular system and restores renal ischemia/reperfusion (I/R) injury by increasing the energy supply to the ischemic tissue and reducing the expression of inflammatory cytokines. Although studies have been reported on the beneficial effects of metformin in I/R of various organs, but the effects and mechanisms of metformin in bladder I/R are still unknown. The purpose of present study is to investigate the effects and mechanisms of metformin against bladder I/R injury in rats. METHODS A total of 60 Spraque-Dawley male rats were randomly divided into three groups (n = 20) including group A- sham operation, group B- bladder I/R and group C- bladder I/R with metformin treatment. An ischemia induce was generated by clamping the bilateral common iliac arteries with atraumatic vascular clamp for 2 hours. After this process, the vascular clamp was removed and the bladder was allowed to reperfusion for 7 days. The rats were injected once in a day for 7 days with 4 mg/kg metformin. Malondialdehyde (MDA), myeloperoxidase (MPO), and superoxide dismutase (SOD) were measured to assess oxidative stress. The expression of MAPKs (such as Erk, JNK and p38 MAPK) and apoptosis-related proteins have detected by Western blotting and RT-PCR. The bladder tissues of rats were assessed by immunohistochemistry analysis of caspase-3. RESULTS Increased MDA levels and MPO activities and decreased SOD activities in the I/R group were reduced by metformin treatment. Compared to the sham group, the I/R group had significantly higher JNK and p38 MAPK levels and lower Erk levels in bladder. However, metformin treatment significantly ameliorated these changes on Western blotting and RT-PCR. The ratio of Bax/Bcl-2 significantly induced in I/R group compared to sham group, and these change significantly reduced after metformin administration. Compared with I/R group, expression level of caspase-3, NF-kB was significantly increased, and these change significantly decreased after metformin treatment. CONCLUSIONS Bladder I/R injury results in the generation of ROS. The findings of the present study showed for the first time that metformin inhibits cell apoptosis and inflammation in I/R induced bladder. Together, the beneficial effects of metformin reducing ROS production may be mediated by regulating the activity of the Erk, JNK, and Bax/Bcl-2 pathways and by controlling NF-kB expression. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e113-e114 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Jong Mok Park More articles by this author Ji Yong Lee More articles by this author Seung Woo Yang More articles by this author Ju Hyun Shin More articles by this author Jae Sung Lim More articles by this author Yong Gil Na More articles by this author Ki Hak Song More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...