Mitochondrial dysfunction as a mechanism involved in the pathogenesis of cirrhosis-associated cholemic nephropathy
| Autor: | Leila Mandegani, Reza Heidari, Negar Azarpira, Hossein Niknahad, Mohammad Mehdi Ommati, Asma Siavashpour, Asma Najibi, Vahid Ghanbarinejad |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Liver Cirrhosis Male Pathology medicine.medical_specialty Cirrhosis Electrolytes imbalance RM1-950 Mitochondrion Bioenergetics medicine.disease_cause digestive system Nephropathy Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Cholestasis medicine Renal fibrosis Animals Pharmacology Kidney business.industry Acute kidney injury General Medicine Energy crisis Acute Kidney Injury medicine.disease Bile acids Mitochondria Rats 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Therapeutics. Pharmacology Lipid Peroxidation business Oxidative stress |
| Zdroj: | Biomedicine & Pharmacotherapy, Vol 109, Iss, Pp 271-280 (2019) |
| ISSN: | 1950-6007 |
| Popis: | Cholemic nephropathy (CN) is a clinical complication associated with cholestasis and chronic liver diseases. CN could lead to renal failure and the need for kidney transplantation if not appropriately managed. On the other hand, although the clinical features of CN are well described, there is no clear idea on the precise cellular and molecular mechanisms of CN. The current study was designed to evaluate kidney mitochondrial function in cholestasis-associated CN. Rats underwent bile duct ligation (BDL) surgery, and kidney mitochondria were isolated at scheduled time intervals (14, 28, and 42 days after BDL operation). Several mitochondrial indices including mitochondrial permeabilization and swelling, glutathione and ATP content, mitochondrial depolarization, and lipid peroxidation were evaluated. Renal tissue markers of oxidative stress along with tissue histopathological changes and serum biochemistry were also analyzed. Severe kidney tissue histopathological alterations including interstitial inflammation, necrosis, and Bowman capsule dilation were detected in the BDL animals. Moreover, drastic elevation in renal fibrosis and collagen deposition was detected in BDL rats. Oxidative stress markers were also significantly enhanced in the kidney tissue of BDL animals. On the other hand, it was found that mitochondrial indices of functionality were significantly deteriorated in BDL rats. These data introduce mitochondrial dysfunction and energy metabolism disturbances as a fundamental mechanism involved in the pathogenesis of bile acids-associated renal injury during cholestasis. |
| Databáze: | OpenAIRE |
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