Metformin alleviates cholestasis-associated nephropathy through regulating oxidative stress and mitochondrial function
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...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2021-09-01
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| Series: | Liver Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2542568420300726 |
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| author | Mohammad Mehdi Ommati Hamidreza Mohammadi Khadijeh Mousavi Negar Azarpira Omid Farshad Reyhaneh Dehghani Asma Najibi Sedigheh Kamran Hossein Niknahad Reza Heidari |
| author_facet | Mohammad Mehdi Ommati Hamidreza Mohammadi Khadijeh Mousavi Negar Azarpira Omid Farshad Reyhaneh Dehghani Asma Najibi Sedigheh Kamran Hossein Niknahad Reza Heidari |
| author_sort | Mohammad Mehdi Ommati |
| collection | DOAJ |
| description | 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 peroxidation, 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. |
| first_indexed | 2024-12-16T09:51:57Z |
| format | Article |
| id | doaj.art-fa5354ea490e42a8b2f51857bd5b1496 |
| institution | Directory Open Access Journal |
| issn | 2542-5684 |
| language | English |
| last_indexed | 2024-12-16T09:51:57Z |
| publishDate | 2021-09-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Liver Research |
| spelling | doaj.art-fa5354ea490e42a8b2f51857bd5b14962022-12-21T22:36:02ZengKeAi Communications Co., Ltd.Liver Research2542-56842021-09-0153171180Metformin alleviates cholestasis-associated nephropathy through regulating oxidative stress and mitochondrial functionMohammad Mehdi Ommati0Hamidreza Mohammadi1Khadijeh Mousavi2Negar Azarpira3Omid Farshad4Reyhaneh Dehghani5Asma Najibi6Sedigheh Kamran7Hossein Niknahad8Reza Heidari9College of Life Sciences, Shanxi Agricultural University, Taigu, Shanxi, ChinaPharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranPharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranTransplant Research Center, Shiraz University of Medical Sciences, Shiraz, IranPharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranDepartment of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranDepartment of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Chemistry, Payame Noor University, Tehran, IranDepartment of Chemistry, Payame Noor University, Tehran, IranPharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; Corresponding authors. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Corresponding authors. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.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 peroxidation, 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.http://www.sciencedirect.com/science/article/pii/S2542568420300726MetforminBile acidsCholestasisCirrhosisOxidative stressMitochondrial function |
| spellingShingle | Mohammad Mehdi Ommati Hamidreza Mohammadi Khadijeh Mousavi Negar Azarpira Omid Farshad Reyhaneh Dehghani Asma Najibi Sedigheh Kamran Hossein Niknahad Reza Heidari Metformin alleviates cholestasis-associated nephropathy through regulating oxidative stress and mitochondrial function Liver Research Metformin Bile acids Cholestasis Cirrhosis Oxidative stress Mitochondrial function |
| title | Metformin alleviates cholestasis-associated nephropathy through regulating oxidative stress and mitochondrial function |
| title_full | Metformin alleviates cholestasis-associated nephropathy through regulating oxidative stress and mitochondrial function |
| title_fullStr | Metformin alleviates cholestasis-associated nephropathy through regulating oxidative stress and mitochondrial function |
| title_full_unstemmed | Metformin alleviates cholestasis-associated nephropathy through regulating oxidative stress and mitochondrial function |
| title_short | Metformin alleviates cholestasis-associated nephropathy through regulating oxidative stress and mitochondrial function |
| title_sort | metformin alleviates cholestasis associated nephropathy through regulating oxidative stress and mitochondrial function |
| topic | Metformin Bile acids Cholestasis Cirrhosis Oxidative stress Mitochondrial function |
| url | http://www.sciencedirect.com/science/article/pii/S2542568420300726 |
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