Sildenafil Attenuates Hepatocellular Injury after Liver Ischemia Reperfusion in Rats: A Preliminary Study

Abstract

We evaluated the role of sildenafil in a rat liver ischemia-reperfusion model. Forty male rats were randomly allocated in four groups. The sham group underwent midline laparotomy only. In the sildenafil group, sildenafil was administered intraperitoneally 60 minutes before sham laparotomy. In the ischemia-reperfusion (I/R) group, rats were subjected to 45 minutes of hepatic ischemia followed by 120 minutes of reperfusion, while in the sild+I/R group rats were subjected to a similar pattern of I/R after the administration of sildenafil, 60 minutes before ischemia. Two hours after reperfusion, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured and histopathological examination of the lobes subjected to ischemia as well as TUNEL staining for apoptotic bodies was performed. Additionally, myeloperoxidase (MPO) activity and the expression of intercellular adhesion molecule-1 (ICAM-1) were analyzed. Serum markers of hepatocellular injury were significantly lower in the sild+I/R group, which also exhibited lower severity of histopathological lesions and fewer apoptotic bodies, as compared to the I/R group. The I/R group showed significantly higher MPO activity and higher expression of ICAM-1, as compared to the sild+I/R group. Use of sildenafil as a preconditioning agent in a rat model of liver I/R exerted a protective effect.

Anti-Inflammatory Effects of Vardenafil Against Cholestatic Liver Damage in Mice: a Mechanistic Study

“…However, vardenafil treatment significantly reversed this pathophysiological state and successfully conferred protection against LCA-induced hepatotoxic effects in a dose-dependent manner. This observation is consistent with previous studies that reported the hepatoprotective effects of PDE-5 inhibitors against ischemic liver injury [15], fatty liver [22], and hepatic fibrosis [14]. Furthermore, our lab recently demonstrated the protective effects of vardenafil against autoimmune hepatitis [17].…”

“…Sildenafil, a selective PDE-5 inhibitor, ameliorates the development of thioacetamide-induced hepatic fibrosis by inhibiting the release of profibrogenic inflammatory cytokines [14]. Furthermore, sildenafil exerts hepatoprotective effects in hepatic ischemia reperfusion injury through the modulation of ICAM and apoptosis [15]. More recently, vardenafil, another selective PDE-5 inhibitor, has been shown to offer protective effects in cystic fibrosis [16] and experimentally induced hepatitis by suppressing oxidative stress and inhibiting the activation of nuclear factor kappa-B (NF-κB) a [17].…”

Protective effect of exercise and sildenafil on acute stress and cognitive function

“…Although in a previous study of our group, the increased MPO levels of brain tissue were observed following electric foot shock stress induction [40]; our study is the first showing the effect of sildenafil pretreatment on elevated MPO levels in stressed conditions. However, several studies have reported the ameliorating effect of sildenafil on MPO levels of inflammation and ischemia-reperfusion (I/R) models [41][42][43][44][45]. Besides, in our study exercise training with or without sildenafil pretreatment prevented MPO levels from rising.…”

Sildenafil potentiates the antitumor activity of cisplatin by induction of apoptosis and inhibition of proliferation and angiogenesis

“…Due to the unexpected side effect of improvement of penile erection, in 1998, sildenafil citrate (Viagra ® ; Pfizer, Inc., New York, NY, USA) became the first PDE-5 inhibitor for the treatment of erectile dysfunction 8. Recently, sildenafil has shown benefits in experimental cardiac dysfunctions,9,10 tissue injury,11–13 cystic fibrosis,14 and ischemia/reperfusion injury 15,16. Additionally, sildenafil as well as other PDE-5 inhibitors were shown to induce apoptosis in different human tumors, such as colon carcinoma and chronic lymphocyte leukemia 17,18.…”