KMID : 1240020210250040285
|
|
International Neurourology Journal 2021 Volume.25 No. 4 p.285 ~ p.295
|
|
Metformin and Sildenafil Attenuate Inflammation and Suppress Apoptosis After Ischemia/Reperfusion Injuries in Rat Urinary Bladder
|
|
Park Jong-Mok
Shin Ju-Hyun Yang Seung-Woo Lee Ji-Yong Lee Chung-Lyul Lim Jae-Sung Song Ki-Hak Kim Gun-Hwa Na Yong-Gil
|
|
Abstract
|
|
|
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-¥êB) 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-¥êB inhibition. However, the combination of metformin and sildenafil was not more effective than either agent alone.
|
|
KEYWORD
|
|
Ischemia-reperfusion, Metformin, Urinary bladder
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|
|