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-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.
ABSTRACT
PURPOSE: Korean red ginseng (KRG) is a potent antioxidant and a free radical scavenger. This study was designed to determine whether KRG could protect against dysfunction and oxidative stress induced by torsion-detorsion injury in rat testis. MATERIALS AND METHODS: Six-week-old male Sprague-Dawley rats were randomly divided into four groups: a sham-operated control group (C), a sham-operated and KRG-treated group (K), a 2 hours torsion and detorsion group (T), and a 2 hours torsion and detorsion and KRG-treated group (T+K). We measured testis weight and hormone levels and reactive oxygen species (ROS) from the left renal vein. Superoxide generation was measured on the basis of lucigenin-enhanced chemiluminescence in testis tissue. RESULTS: Testicular weight was significantly higher in the T+K group than in the T group; however, there were no significant differences in hormone levels between the 4 groups. The mean level of ROS and superoxide production was significantly higher in the T group than in the C group, whereas administration of KRG attenuated this increase. Upon histologic evaluation, the T group was found to have cellular disarray, a lack of cellular cohesiveness, degenerative changes in the germinal cells, and less distinct changes in the seminiferous tubules, whereas the T+K group had a germinal epithelial layer that appeared nearly normal. CONCLUSIONS: The present study demonstrated that KRG recovered the testis dysfunction in the rat testis by suppressing superoxide production.