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

作　　者：Mohammad Mehdi Ommati Hamidreza Mohammadi Khadijeh Mousavi Negar Azarpira Omid Farshad Reyhaneh Dehghani Asma Najibi Sedigheh Kamran Hossein Niknahad Reza Heidari 

机构地区：[1]College of Life Sciences,Shanxi Agricultural University,Taigu,Shanxi,China [2]Pharmaceutical Sciences Research Center,Shiraz University of Medical Sciences,Shiraz,Iran [3]Department of Pharmacology and Toxicology,School of Pharmacy,Shiraz University of Medical Sciences,Shiraz,Iran [4]Transplant Research Center,Shiraz University of Medical Sciences,Shiraz,Iran [5]Department of Chemistry,Payame Noor University,Tehran,Iran

出　　处：《Liver Research》2021年第3期171-180,共10页肝脏研究（英文）

基　　金：This work was financially supported by the Vice-Chancellor of Research Affairs of Shiraz University of Medical Sciences,Shiraz,Iran(Grant No.19444).

摘　　要：Background and aim:Cholestasis-associated renal injury or cholemic nephropathy(CN)is a serious clinical problem.Previous studies mentioned that oxidative stress and mitochondrial impairment play a role in CN.There is no specific pharmacological intervention for CN.Metformin is an anti-diabetic drug administered for decades.On the other hand,novel pharmacological properties have emerged for this drug.The effect of metformin on oxidative stress parameters has been well-recognized in different experimental models.It has also been found that metformin positively affected mitochondrial function.The current study aimed to evaluate the effects of metformin in an animal model of CN.Methods:Rats underwent bile duct ligation(BDL)and were treated with metformin(250 and 500 mg/kg)for 14 consecutive days.Two weeks after the BDL operations,urine,serum,and kidney samples were collected and analyzed.Results: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 animals.Moreover,mitochondrial indices,including adenosine triphosphate(ATP)level,dehydrogenase activity,mitochondrial membrane potential,and mitochondrial permeability,were impaired in the kidney of cholestatic rats.Renal histopathological alterations in cholestatic animals included tubular degeneration and interstitial inflammation,cast formation,and fibrosis.It was found that metformin significantly alleviated oxidative stress and improved mitochondrial indices in the kidney of cholestatic rats.Tissue histopathological alterations were also mitigated in metformin-treated groups.Conclusions:Metformin could be a candidate for managing CN.The 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 

分 类 号：R692[医药卫生—泌尿科学]