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Metformin alleviates cholestasis-associated nephropathy through regulating oxidative stress and mitochondrial function

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Liver Research 2021年第3期5卷 171-180页

作者： Mohammad Mehdi Ommati Hamidreza Mohammadi Khadijeh Mousavi Negar Azarpira Omid Farshad Reyhaneh Dehghani Asma Najibi Sedigheh Kamran hossein niknahad Reza Heidari College of Life Sciences Shanxi Agricultural UniversityTaiguShanxiChina Pharmaceutical Sciences Research Center Shiraz University of Medical SciencesShirazIran Department of Pharmacology and Toxicology School of PharmacyShiraz University of Medical SciencesShirazIran Transplant Research Center Shiraz University of Medical SciencesShirazIran Department of Chemistry Payame Noor UniversityTehranIran

Background and aim:Cholestasis-associated renal injury or cholemic nephropathy(CN)is a serious clinical *** studies mentioned that oxidative stress and mitochondrial impairment play a role in *** is no specific pharmacological intervention for *** is an anti-diabetic drug administered for *** the other hand,novel pharmacological properties have emerged for this *** effect of metformin on oxidative stress parameters has been well-recognized in different experimental *** has also been found that metformin positively affected mitochondrial *** current study aimed to evaluate the effects of metformin in an animal model of ***:Rats underwent bile duct ligation(BDL)and were treated with metformin(250 and 500 mg/kg)for 14 consecutive *** weeks after the BDL operations,urine,serum,and kidney samples were collected and ***:Markers of oxidative stress,including reactive oxygen species(ROS)formation,lipid peroxida-tion,protein carbonylation,depleted antioxidant capacity,and decreased glutathione(GSH)levels were detected in BDL ***,mitochondrial indices,including adenosine triphosphate(ATP)level,dehydrogenase activity,mitochondrial membrane potential,and mitochondrial permeability,were impaired in the kidney of cholestatic *** histopathological alterations in cholestatic animals included tubular degeneration and interstitial inflammation,cast formation,and *** was found that metformin significantly alleviated oxidative stress and improved mitochondrial indices in the kidney of cholestatic *** histopathological alterations were also mitigated in metformin-treated ***:Metformin could be a candidate for managing *** nephroprotective role of metformin is primarily associated with its effects on oxidative stress parameters and mitochondrial function.

关键词： Metformin Bile acids Cholestasis Cirrhosis Oxidative stress Mitochondrial function Energy crisis Cholemic nephropathy(CN) Renal failure

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