Preconditioning and anti-apoptotic effects of Metformin and Cyclosporine-A in an isolated bile duct-ligated rat heart

Autor: Ayesheh Enayati, Zohreh Mazaheri, Hamid Reza Moheimani, Mona Pourabouk, Parham Sayyah Ensan, Mohammad Ali Zeyghami, Yahya Jand, Taghi Amiriani, Ahmad Reza Dehpour, Maryam Rajaei, Amir Hoshang Pourkhani, Vahid Khori, Delaram Shakiba, Ali Mohammad Alizadeh, Fatemeh Jafarzadeh, Shahriar Aliazadeh
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Cirrhosis
Ischemia
Myocardial Infarction
Hemodynamics
Apoptosis
Myocardial Reperfusion Injury
Pharmacology
AMP-Activated Protein Kinases
Liver Cirrhosis
Experimental
digestive system
03 medical and health sciences
0302 clinical medicine
Cyclosporin a
Medicine
Animals
Myocytes
Cardiac
cardiovascular diseases
Rats
Wistar
Ligation
business.industry
Bile duct
Mitochondrial Permeability Transition Pore
Isolated Heart Preparation
medicine.disease
digestive system diseases
Cirrhotic cardiomyopathy
Metformin
Enzyme Activation
030104 developmental biology
medicine.anatomical_structure
Cytoprotection
Ischemic Preconditioning
Myocardial
Cyclosporine
Ischemic preconditioning
Bile Ducts
business
Apoptosis Regulatory Proteins
Cardiomyopathies
030217 neurology & neurosurgery
medicine.drug
Signal Transduction
Zdroj: European journal of pharmacology. 893
ISSN: 1879-0712
Popis: Despite all previous studies relating to the mechanism of cirrhotic cardiomyopathy (CCM), the role of cirrhosis on Ischemic Preconditioning (IPC) has not yet been explored. The present study strives to assess the cardioprotective role of IPC in bile duct ligated (BDL) rats as well as the cardioprotective role of Cyclosporin-A (CsA) and Metformin (Met) in CCM. Cirrhosis was induced by bile duct ligation (BDL). Rats' hearts were isolated and attached to a Langendorff Apparatus. The pharmacological preconditioning with Met and CsA was done before the main ischemia. Myocardial infarct size, hemodynamic and electrophysiological parameters, biochemical markers, and apoptotic indices were determined at the end of the experiment. Infarct size, apoptotic indices, arrhythmia score, and incidence of VF decreased significantly in the IPC group in comparison with the I/R group. These significant decreases were abolished in the IPC (BDL) group. Met significantly decreased the infarct size and apoptotic indices compared with I/R (BDL) and normal groups, while CsA led to similar decreases except in the level of caspase-3 and -8. Met and CsA decreased and increased the arrhythmia score and incidence of VF in the BDL groups, respectively. Functional recovery indices decreased in the I/R (BDL) and IPC (BDL) groups. Met improved these parameters. Therefore, the current study depicted that the cardioprotective effect of Met and CsA on BDL rats is mediated through the balance between pAMPK and apoptosis in the mitochondria.
Databáze: OpenAIRE
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