Mitigation of cholestasis-associated hepatic and renal injury by edaravone treatment: Evaluation of its effects on oxidative stress and mitochondrial function

Abstract

Background and aimThe liver is the primary organ affected by cholestasis, and complications such as renal injury, renal failure, and the need for renal transplantation are associated with cholestatic liver disease. There is substantial evidence indicating that reactive oxygen species (ROS) and mitochondrial impairment are fundamental mechanisms underlying cholestasis-induced hepatic and renal injury. Edaravone (EDV) is a potent radical scavenger and antioxidant that may prevent oxidative stress and improve impaired mitochondrial function in various diseases. This study was performed to evaluate the effects and mechanisms of action of EDV on hepatic and renal injury in an animal model of cholestasis. MethodsRats subjected to bile duct ligation (BDL) were treated with EDV 1 or 10 mg/kg/day intraperitoneally for 14 consecutive days. Biomarkers of oxidative stress and mitochondrial impairment in the liver and kidney were assessed in EDV-treated and untreated rats with cholestasis. ResultsSignificant increases in tissue ROS level, lipid peroxidation, protein carbonylation, and oxidized glutathione level were detected in rats subjected to BDL. Additionally, significant decreases in tissue glutathione level and antioxidant capacity were observed in the hepatic and renal tissues of rats with cholestasis. Markers of mitochondrial impairment, including mitochondrial depolarization, lipid peroxidation, mitochondrial permeabilization, depleted adenosine triphosphate content, and decreased dehydrogenase activity, were also detected in rats subjected to BDL. Furthermore, portal inflammation, necrosis, and tissue fibrosis were detected in the liver and significant tubular atrophy and interstitial inflammation, as well as fibrotic lesions, were detected in the kidneys of rats with cholestasis. EDV treatment significantly mitigated cholestasis-associated hepatic and renal injury. ConclusionsThe antioxidative properties of EDV and its positive effects on the indices of mitochondrial function may be critical factors contributing to protection against cholestasis-associated hepatic and renal injury.