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

Autor: Moheimani HR; Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran., Amiriani T; Golestan Research Center of Gastroenterology and Hepatology, Gorgan, Iran., Alizadeh AM; Cancer Research Center of Institute Cancer, Tehran University of Medical Science, Tehran, Iran., Jand Y; Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran., Shakiba D; Department of Mechanical Engineering and Material Science, Washington University in St. Louis, St. Louis, MO, USA., Ensan PS; Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran., Jafarzadeh F; Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran., Rajaei M; Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran., Enayati A; Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran., Pourabouk M; Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran., Aliazadeh S; Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran., Pourkhani AH; Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran., Mazaheri Z; Basic Medical Science Research Center, Histogenotech Company, Tehran, Iran., Zeyghami MA; Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran., Dehpour A; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: dehpoura@sina.tums.ac.ir., Khori V; Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran. Electronic address: vahid.khori@yahoo.com.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2021 Feb 15; Vol. 893, pp. 173807. Date of Electronic Publication: 2021 Jan 05.
DOI: 10.1016/j.ejphar.2020.173807
Abstrakt: 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.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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