Ameliorative Effects of Sildenafil in Acetic Acid-Induced Chronic Colitis in Rats

作者：Ahmed Osama M^*; Afifi Alaa; Ali Tarek M; Ramadan Shimaa A; Mahmoud Ayman M

来源：Life Science Journal-Acta Zhengzhou University Overseas Edition, 2012, 9(1): 354-361.

• Sildenafil
• Acetic acid-induced colitis
• Oxidative stress
• Pro-inflammatroy cytokines

This study aims to assess the effect of sildenafil citrate, a potent inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE) 5, on the colon histological integrity, oxidant-antioxidant status and pro-inflammatory cytokines in a rat model of acetic acid-induced colitis. Chronic colitis was induced under light ether anesthesia by intrarectal administration of 1 ml of 5% (v/v) acetic acid (AA) in male albino rats, with a second intrarectal administration of the same dose after 16 days. Control rats received an equal volume of saline intrarectally. Experimental rats were treated orally with either sildenafil citrate (5 and 10 mg/kg/day) or saline for 3 days. Tissue samples were used for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels, and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities. Blood was collected for the assessment of serum AST, ALT, creatinine, urea, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta levels. Obtained results revealed that in colitis group, the colonic tissue was characterized by lesions such as cystic dilatation, hemorrhage, and leukocytic infilterations, increased lipid peroxidation with a concomitant reduction in GSH content, and decreased GPx and SOD activities. Serum hepatic and renal function parameters, TNF-alpha and IL-1 beta levels were higher in the colitis group compared to control values. Sildenafil, in a dose dependent manner, reversed these parameters nearly back to control values. In conclusion, sildenafil citrate administration to rats with chronic AA-induced colitis seems to be beneficial via prevention of inflammatory processes, lipid peroxidation, cytokine production and alleviation of the anti-oxidant defense system. [Osama M. Ahmed, Alaa Afifi, Tarek M. Ali, Shimaa A. Ramadan and Ayman M. Mahmoud. Ameliorative Effects of Sildenafil in Acetic Acid-Induced Chronic Colitis in Rats. Life Science Journal 2012; 9(1):354-361]. (ISSN: 1097-8135). http://www.lifesciencesite.com. 51

• 出版日期2012