Background and aim:The 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...Background and aim:The 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.Methods:Rats subjected to bile duct ligation(BDL)were treated with EDV 1 or 10 mg/kg/day intraper-itoneally 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.Results:Significant 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 perox-idation,mitochondrial permeabilization,depleted adenosine triphosphate content,and decreased de-hydrogenase 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.Conclusions:The 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.展开更多
基金This study was financially supported by the Vice-Chancellor of Research Affairs of Shiraz University of Medical Sciences(Grant number:97-01-36-18730)Shanxi Agricultural University(Grant numbers:2018YJ33 and K271999031 for National Natural Science Foundation of China and Outstanding Doctors Volunteering to Work in Shanxi Province,respectively).
文摘Background and aim:The 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.Methods:Rats subjected to bile duct ligation(BDL)were treated with EDV 1 or 10 mg/kg/day intraper-itoneally 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.Results:Significant 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 perox-idation,mitochondrial permeabilization,depleted adenosine triphosphate content,and decreased de-hydrogenase 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.Conclusions:The 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.
