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Int Neurourol J > Accepted Articles
DOI:    [Accepted]
Metformin and Sildenafil Attenuate Inflammation and Suppress Apoptosis After Ischemia/Reperfusion Injury in Rat Urinary Bladder
Jong MoK Park1, Ju Hyun Shin2, Seung Woo Yang2, Ji Yong Lee2, Chung Lyul Lee2, Jae Sung Lim2, Ki Hak Song2, Gun Hwa Kim3, Yong Gil Na1
1Department of Urology, Chungnam National University Sejong Hospital, Chungnam National University School of Medicine, Sejong, Korea
2Department of Urology, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Korea
3Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju, Korea
Correspondence  Yong Gil Na ,Email:
Submitted: 1 July 2021;  Accepted after revision: 3 September 2021.
Although metformin and sildenafil can protect various organs against ischemia/reperfusion (I/R) injury, their effects and mechanisms of action in bladder I/R injury remain unknown. This study investigated the effects and mechanisms of action of metformin and sildenafil against bladder I/R insult in rats.
One hundred male Sprague–Dawley rats were randomly divided into five groups each of twenty rats: a sham-operated group, a bladder I/R group, and bladder I/R groups treated with metformin, sildenafil, or both agents. Ischemia was induced by clamping the bilateral common iliac arteries with atraumatic vascular clamps for 2 hours, followed by reperfusion for 7 days. During this period, rats were injected once daily with 4 mg/kg metformin and/or 1 mg/kg sildenafil.
The increased malondialdehyde (MDA) levels and myeloperoxidase (MPO) activities and the decreased superoxide dismutase (SOD) activities induced by I/R injury were reduced by treatment with metformin and/or sildenafil. The I/R group had significantly higher JNK, p38 MAPK, Bax, caspase-3, and NF-κB levels, and lower ERK and Bcl-2 levels in the bladder than the sham-operated group; these changes were significantly ameliorated by metformin and/or sildenafil treatment. No differences in the levels of these markers were observed between rats co-administered metformin and sildenafil and those treated with either agent alone.
Metformin and sildenafil protected rat bladder against I/R injury. This effect may be due to the inhibition of ROS production through MAPKs, Bax, and Bcl-2 activation, and the restoration of inflammation through NF-κB inhibition. However, the combination of metformin and sildenafil was no more effective than either agent alone.
Keywords: Ischemia-reperfusion; Metformin; Urinary bladder
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