Biliary cirrhosis-induced cardiac abnormality in rats: Interaction between Farnesoid-X-activated receptors and the cardiac uncoupling proteins 2 and 3
Objective(s): This study aimed to evaluate the relationship between Farnesoid-X-activated receptors (FXR) as nuclear regulators of the antioxidant defense system as well as cardiac mitochondrial carrier proteins of UCP2 and UCP3 in cardiac damage induced by cirrhosis. Materials and Methods: Twenty-t...
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| Format: | Article |
| Language: | English |
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Mashhad University of Medical Sciences
2022-01-01
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| Series: | Iranian Journal of Basic Medical Sciences |
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| Online Access: | https://ijbms.mums.ac.ir/article_19499_c68621b1f16a2e3808af654c208eb07b.pdf |
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| author | Gholamreza Bayat Seyed Ali Hashemi Hosein Karim Parviz Fallah Keshvad Hedayatyanfard Mahnaz Bayat Azadeh Khalili |
| author_facet | Gholamreza Bayat Seyed Ali Hashemi Hosein Karim Parviz Fallah Keshvad Hedayatyanfard Mahnaz Bayat Azadeh Khalili |
| author_sort | Gholamreza Bayat |
| collection | DOAJ |
| description | Objective(s): This study aimed to evaluate the relationship between Farnesoid-X-activated receptors (FXR) as nuclear regulators of the antioxidant defense system as well as cardiac mitochondrial carrier proteins of UCP2 and UCP3 in cardiac damage induced by cirrhosis. Materials and Methods: Twenty-two male Wistar rats (200–250 g) were randomly divided into 3 experimental groups, including a control group (n=6), a sham-operated group (n=8), and a bile duct ligated (BDL) group (n=8). Four weeks after surgical intervention, biochemical assessment (AST, ALT, GGT, LDH, and ALP), histological observation, and molecular evaluation (FXR, UCP2, UCP3, BNP, Caspase3, and GAPDH) using real-time RT-PCR were performed. Results: Compared with the sham-operation group, the BDL group showed a significant rise in liver enzymes of AST, ALT, GGT, LDH, and ALP. Defined fibrotic and necrotic bundles and thick reticulin fibers were also found in BDL liver tissue. Besides liver morphological alterations, left ventricles of BDL ones were also associated with defined cardiomyocyte hypertrophy, myofiber vacuolization, and clear pigmentation. Findings showed a significant up-regulation of cardiac Brain Natriuretic Peptide (BNP) along with marked down-regulation in hepatic FXR, cardiac FXR, and cardiac UCP2 and UCP3. However, the expression of caspase 3 in the cardiac tissue was not affected by BDL operation during 4 weeks. Conclusion: Expression of FXR as an upstream regulator of cellular redox status, besides the non-enzymatic ROS buffering defense system of cardiac UCPs, has a pivotal role in the pathogenesis of cirrhotic-induced cardiac abnormality in rats. |
| first_indexed | 2024-12-21T14:15:47Z |
| format | Article |
| id | doaj.art-7c71bbf78820428a88156ccdac3c1889 |
| institution | Directory Open Access Journal |
| issn | 2008-3866 2008-3874 |
| language | English |
| last_indexed | 2024-12-21T14:15:47Z |
| publishDate | 2022-01-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj.art-7c71bbf78820428a88156ccdac3c18892022-12-21T19:00:56ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742022-01-0125112613310.22038/ijbms.2022.60888.1348519499Biliary cirrhosis-induced cardiac abnormality in rats: Interaction between Farnesoid-X-activated receptors and the cardiac uncoupling proteins 2 and 3Gholamreza Bayat0Seyed Ali Hashemi1Hosein Karim2Parviz Fallah3Keshvad Hedayatyanfard4Mahnaz Bayat5Azadeh Khalili6Department of Physiology-Pharmacology-Medical Physic, School of Medicine, Alborz University of Medical Sciences, Karaj, IranDepartment of Pathology, School of Medicine, Alborz University of Medical Sciences, Karaj, IranCardiovascular Research Center, Alborz University of Medical Sciences, Karaj, IranDepartment of Medical Laboratory Sciences, Faculty of Para-Medicine, Alborz University of Medical Sciences, Karaj, IranDepartment of Physiology-Pharmacology-Medical Physic, School of Medicine, Alborz University of Medical Sciences, Karaj, IranClinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, IranDepartment of Physiology-Pharmacology-Medical Physic, School of Medicine, Alborz University of Medical Sciences, Karaj, IranObjective(s): This study aimed to evaluate the relationship between Farnesoid-X-activated receptors (FXR) as nuclear regulators of the antioxidant defense system as well as cardiac mitochondrial carrier proteins of UCP2 and UCP3 in cardiac damage induced by cirrhosis. Materials and Methods: Twenty-two male Wistar rats (200–250 g) were randomly divided into 3 experimental groups, including a control group (n=6), a sham-operated group (n=8), and a bile duct ligated (BDL) group (n=8). Four weeks after surgical intervention, biochemical assessment (AST, ALT, GGT, LDH, and ALP), histological observation, and molecular evaluation (FXR, UCP2, UCP3, BNP, Caspase3, and GAPDH) using real-time RT-PCR were performed. Results: Compared with the sham-operation group, the BDL group showed a significant rise in liver enzymes of AST, ALT, GGT, LDH, and ALP. Defined fibrotic and necrotic bundles and thick reticulin fibers were also found in BDL liver tissue. Besides liver morphological alterations, left ventricles of BDL ones were also associated with defined cardiomyocyte hypertrophy, myofiber vacuolization, and clear pigmentation. Findings showed a significant up-regulation of cardiac Brain Natriuretic Peptide (BNP) along with marked down-regulation in hepatic FXR, cardiac FXR, and cardiac UCP2 and UCP3. However, the expression of caspase 3 in the cardiac tissue was not affected by BDL operation during 4 weeks. Conclusion: Expression of FXR as an upstream regulator of cellular redox status, besides the non-enzymatic ROS buffering defense system of cardiac UCPs, has a pivotal role in the pathogenesis of cirrhotic-induced cardiac abnormality in rats.https://ijbms.mums.ac.ir/article_19499_c68621b1f16a2e3808af654c208eb07b.pdfcardiomyopathycholestasisfarnesoid-x-receptorliver cirrhosismitochondrial uncoupling proteins |
| spellingShingle | Gholamreza Bayat Seyed Ali Hashemi Hosein Karim Parviz Fallah Keshvad Hedayatyanfard Mahnaz Bayat Azadeh Khalili Biliary cirrhosis-induced cardiac abnormality in rats: Interaction between Farnesoid-X-activated receptors and the cardiac uncoupling proteins 2 and 3 Iranian Journal of Basic Medical Sciences cardiomyopathy cholestasis farnesoid-x-receptor liver cirrhosis mitochondrial uncoupling proteins |
| title | Biliary cirrhosis-induced cardiac abnormality in rats: Interaction between Farnesoid-X-activated receptors and the cardiac uncoupling proteins 2 and 3 |
| title_full | Biliary cirrhosis-induced cardiac abnormality in rats: Interaction between Farnesoid-X-activated receptors and the cardiac uncoupling proteins 2 and 3 |
| title_fullStr | Biliary cirrhosis-induced cardiac abnormality in rats: Interaction between Farnesoid-X-activated receptors and the cardiac uncoupling proteins 2 and 3 |
| title_full_unstemmed | Biliary cirrhosis-induced cardiac abnormality in rats: Interaction between Farnesoid-X-activated receptors and the cardiac uncoupling proteins 2 and 3 |
| title_short | Biliary cirrhosis-induced cardiac abnormality in rats: Interaction between Farnesoid-X-activated receptors and the cardiac uncoupling proteins 2 and 3 |
| title_sort | biliary cirrhosis induced cardiac abnormality in rats interaction between farnesoid x activated receptors and the cardiac uncoupling proteins 2 and 3 |
| topic | cardiomyopathy cholestasis farnesoid-x-receptor liver cirrhosis mitochondrial uncoupling proteins |
| url | https://ijbms.mums.ac.ir/article_19499_c68621b1f16a2e3808af654c208eb07b.pdf |
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