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Mitochondrial dysfunction as a mechanism involved in the pathogenesis of Cirrhosisassociated cholemic nephropathy

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Year: 2019
COI code: TOXICOLOGY15_127
Paper Language: English

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Authors Mitochondrial dysfunction as a mechanism involved in the pathogenesis of Cirrhosisassociated cholemic nephropathy

  Reza Heidari - Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz Iran
  Leila Mandegani - Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University ofMedical Sciences, Shiraz Iran
  Vahid Ghanbarinejad - Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University ofMedical Sciences, Shiraz Iran
  Asma Siavashpour - Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University ofMedical Sciences, Shiraz Iran
  Mohammad Mehdi Ommati - Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz Iran- Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University ofMedical Sciences, Shiraz Iran
  Asma Najibi - Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University ofMedical Sciences, Shiraz Iran

Abstract:

Cholemic nephropathy (CN) is a clinical complication associated with cholestasis and chronicliver diseases. CN could lead to renal failure and 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.

Keywords:

Acute kidney injury; Bile acids; Bioenergetics; Cirrhosis; Electrolytes imbalance; Energy crisis; Mitochondria

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COI code: TOXICOLOGY15_127

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Heidari, Reza; Leila Mandegani; Vahid Ghanbarinejad; Asma Siavashpour; Mohammad Mehdi Ommati & Asma Najibi, 2019, Mitochondrial dysfunction as a mechanism involved in the pathogenesis of Cirrhosisassociated cholemic nephropathy, 15th iranian congress of toxicology, تهران, دانشگاه علوم پزشكي شهيد بهشتي, https://www.civilica.com/Paper-TOXICOLOGY15-TOXICOLOGY15_127.htmlInside the text, wherever referred to or an achievement of this article is mentioned, after mentioning the article, inside the parental, the following specifications are written.
First Time: (Heidari, Reza; Leila Mandegani; Vahid Ghanbarinejad; Asma Siavashpour; Mohammad Mehdi Ommati & Asma Najibi, 2019)
Second and more: (Heidari; Mandegani; Ghanbarinejad; Siavashpour; Ommati & Najibi, 2019)
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Type: Medical University
Paper No.: 2097
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