Sildenafil blunts cholestasis-associated cholemic nephropathy in a rat model of bile duct ligation
Abstract
Aim of the study Cholestasis is characterized by impaired bile flow from the liver to the small intestine. Beyond liver damage, cholestasis significantly affects other organs, particularly the kidneys, causing a condition known as cholemic nephropathy (CN). Sildenafil is a phosphodiesterase type 5 (PDE5) enzyme inhibitor with a wide range of pharmacological effects. Several studies have described the nephroprotective properties of sildenafil. Material and methods Rats underwent bile duct ligation (BDL) surgery to induce cholestasis and CN. Afterward, BDL animals received sildenafil (5, 10, and 20 mg/kg/day, i.p., for 14 consecutive days). Urine, blood, and kidney samples were collected for further evaluation. Results Elevated levels of blood urea nitrogen (BUN) and creatinine (Cr) and urinalysis revealed renal injury in this model (p < 0.001). Oxidative stress markers, including depleted antioxidant capacity, increased ROS formation, lipid peroxidation, and protein carbonylation, were evident in the kidneys of BDL rats (p < 0.001). Moreover, the activity of enzymatic antioxidant systems (CAT, SOD, GR, and GPx) was also significantly decreased in the kidney of BDL animals (p < 0.001). Tissue pro-inflammatory cytokines (TNF-a, IL-6, and IL-1b) were also considerably higher in the kidney of cholestatic rats (p < 0.001). Renal histopathological changes in BDL animals included inflammatory cell infiltration, tubular atrophy, necrosis, significant fibrotic changes, and cast…
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