Sildenafil Blunts Lung Inflammation and Oxidative Stress in a Rat Model of Cholestasis

Background: Cholestasis is a multifaceted disease that influences not only the function of the liver but also affects many other organs. In this context, cholestasis-induced lung injury is a significant clinical complication. Unfortunately, there is no precise therapeutic option against cholestasis-associated lung injury. It has been revealed that oxidative stress and inflammatory response play a role in cholestasis-induced pulmonary damage. Sildenafil is a phosphodiesterase enzyme inhibitor used in the management of erectile dysfunction. Meanwhile, several experiments revealed the effects of sildenafil on oxidative stress and inflammation. This study aimed to evaluate the effect of sildenafil on cholestasis-induced oxidative stress and inflammation in cholestasis-induced lung injury.

Methods: Rats underwent bile duct ligation (BDL) to induce cholestasis. Bronchoalveolar lavage fluid (BALF) levels of inflammatory cells, cytokine, and immunoglobulin were monitored at (3, 7, and 14 days after BDL surgery). Moreover, lung tissue histopathological alterations and biomarkers of oxidative stress were evaluated.

Results: A significant increase in BALF inflammatory cells, TNF-α, and immunoglobulin G (IgG) was evident in BDL animals. Moreover, the infiltration of inflammatory cells, vascular congestion, and hemorrhage were detected in the lung of BDL rats. Increased markers of oxidative stress were also evident in the lung of BDL animals. Sildenafil (10 and 20 mg/kg) significantly blunted inflammatory response, oxidative stress, and histopathological alterations in the lung of cholestatic animals.

Conclusion: The effects of sildenafil on inflammatory response and oxidative stress biomarkers seems to play a crucial role in its protective properties in the lung of cholestatic animals.