Metformin and Sildenafil Attenuate Inflammation and Suppress Apoptosis After Ischemia/Reperfusion Injuries in Rat Urinary Bladder

• Published in: International neurourology journal Vol. 25; no. 4; pp. 285 - 295
• Main Authors: Park, Jong Mok, Shin, Ju Hyun, Yang, Seung Woo, Lee, Ji Yong, Lee, Chung Lyul, Lim, Jae Sung, Song, Ki Hak, Kim, Gun Hwa
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Continence Society 01.12.2021; 대한배뇨장애요실금학회
• Subjects: ischemia-reperfusion; metformin; Original; urinary bladder; 비뇨기과학; Ischemia-reperfusion; Urinary bladder; Metformin
• ISSN: 2093-6931; 2093-4777; 2093-6931
• DOI: 10.5213/inj.2142206.103

Purpose: Although metformin and sildenafil can protect various organs against ischemia/reperfusion (I/R) injuries, their effects and mechanisms of action in bladder I/R injuries remain unknown. This study investigated the effects and mechanisms of action of metformin and sildenafil against bladder I/R insults in rats.Methods: One hundred male Sprague-Dawley rats were randomly divided into 5 groups, each of which contained 20 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.Results: I/R injuries induced increased malondialdehyde levels and myeloperoxidase activity and decreased superoxide dismutase activity. These changes were attenuated by treatment with metformin and/or sildenafil. The I/R group had significantly higher Jun N-terminal kinase, p38 mitogen-activated protein kinase (MAPK), Bax, caspase-3, and nuclear factor-kappa B (NF-κB) levels, and lower extracellular signal-regulated kinase, 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 coadministered metformin and sildenafil and those treated with either agent alone.Conclusions: Metformin and sildenafil protected the rat bladder against I/R injuries. This effect may have been due to the inhibition of reactive oxygen species production through MAPK, Bax, and Bcl-2 activation, and the restoration of inflammation through NF-κB inhibition. However, the combination of metformin and sildenafil was not more effective than either agent alone.