Hepatoprotective role of vardenafil against experimentally induced hepatitis in mice

Abstract

Vardenafil is a selective phosphodiesterase-5 inhibitor used for erectile dysfunction treatment. The hepatoprotective role of vardenafil against acute hepatitis is not reported yet. Hence, this study aims to explore the protective role of vardenafil against concanavalin A (Con A) induced acute liver injury. Mice were pretreated with vardenafil (0.17 mg/kg/day) for seven consecutive days, and then subjected to a single IV injection of Con A. The results demonstrated that the vardenafil pretreatment significantly reduced the elevated serum levels of transaminases and alkaline phosphatase. Histopathological examination showed marked necrosis and inflammation in Con A-treated mice which was significantly ameliorated in vardenafil pretreated animals. Vardenafil pretreatment significantly alleviated the expression of nuclear factor kappa-B and inducible nitric oxide synthase in the hepatic tissue. Additionally, serum levels of nitric oxide and tumor necrosis factor-alpha were decreased in vardenafil pretreated animals compared to the Con A group. Therefore, our results demonstrate that vardenafil has hepatoprotective effect and this could be linked to decrease inflammatory mediators.

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

“…Our data showed that LCA induced the activation of NF-κB and markedly increased the release of inflammatory cytokines, and these effects were greatly reduced by vardenafil treatment. These findings are consistent with previous investigations that showed the ability of vardenafil to suppress NF-κB activation and subsequently the release of inflammatory cytokines in autoimmune hepatitis [17] and lung inflammation [42].…”

“…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].…”

“…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].…”

Alpha-Mangostin as a New Therapeutic Candidate for Concanavalin A-Induced Autoimmune Hepatitis: Impact on the SIRT1/Nrf2 and NF-κB Crosstalk

“…The Con A was dissolved in normal saline (Sigma-Aldrich, St. Louis, MO, USA) and was used to induce AIH via one intravenous dose (15 mg/kg) as described previously [8,25]. The mice were assigned to five groups (eight mice each) and received the treatment as follows:…”

“…A convenient animal model that resembles AIH in humans has been well established using a single dose of concanavalin A (Con A) which is a lectin derived from the Canavalia ensiformis extract [8]. Con A-induced hepatitis has a ubiquitous role and specificity in the activation of direct T-cells.…”