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

Hamid Reza Moheimani; Taghi Amiriani; Ali Mohammad Alizadeh; Yahya Jand; Delaram Shakiba; Parham Sayyah Ensan; Fatemeh Jafarzadeh; Maryam Rajaei; Ayesheh Enayati; Mona Pourabouk; Shahriar Aliazadeh; Amir Hoshang Pourkhani; Zohreh Mazaheri; Mohammad Ali Zeyghami; Ahmadreza Dehpour; Vahid Khori

doi:10.1016/j.ejphar.2020.173807

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

Hamid Reza Moheimani
, Taghi Amiriani
, Ali Mohammad Alizadeh
, Yahya Jand
, Delaram Shakiba
, Parham Sayyah Ensan
, Fatemeh Jafarzadeh
, Maryam Rajaei
, Ayesheh Enayati
, Mona Pourabouk
, Shahriar Aliazadeh
, Amir Hoshang Pourkhani
, Zohreh Mazaheri
, Mohammad Ali Zeyghami
, Ahmadreza Dehpour
, Vahid Khori

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Article number	173807
Journal	European Journal of Pharmacology
Volume	893
DOIs	https://doi.org/10.1016/j.ejphar.2020.173807
State	Published - Feb 15 2021
Externally published	Yes

Keywords

Bile duct ligation
Caspase
Cyclosporin-A
Cyclosporin-A (3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-Ethyl-33-[(E,1R,2R)-1-Hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone, PubChemCID: 5284373
Ischemic preconditioning
Metformin
Metformin 3-(diaminomethylidene)-1,1-dimethylguanidine, PubChem CID:4091

ASJC Scopus subject areas

Pharmacology

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10.1016/j.ejphar.2020.173807

Cite this

Moheimani, H. R., Amiriani, T., Alizadeh, A. M., Jand, Y., Shakiba, D., Ensan, P. S., Jafarzadeh, F., Rajaei, M., Enayati, A., Pourabouk, M., Aliazadeh, S., Pourkhani, A. H., Mazaheri, Z., Zeyghami, M. A., Dehpour, A., & Khori, V. (2021). Preconditioning and anti-apoptotic effects of Metformin and Cyclosporine-A in an isolated bile duct-ligated rat heart. European Journal of Pharmacology, 893, Article 173807. https://doi.org/10.1016/j.ejphar.2020.173807

Moheimani, HR, Amiriani, T, Alizadeh, AM, Jand, Y, Shakiba, D, Ensan, PS, Jafarzadeh, F, Rajaei, M, Enayati, A, Pourabouk, M, Aliazadeh, S, Pourkhani, AH, Mazaheri, Z, Zeyghami, MA, Dehpour, A & Khori, V 2021, 'Preconditioning and anti-apoptotic effects of Metformin and Cyclosporine-A in an isolated bile duct-ligated rat heart', European Journal of Pharmacology, vol. 893, 173807. https://doi.org/10.1016/j.ejphar.2020.173807

@article{439ed313c30c4655a1511e0ee8b2a111,

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

abstract = "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{\textquoteright} 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.",

keywords = "Bile duct ligation, Caspase, Cyclosporin-A, Cyclosporin-A (3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-Ethyl-33-[(E,1R,2R)-1-Hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone, PubChemCID: 5284373, Ischemic preconditioning, Metformin, Metformin 3-(diaminomethylidene)-1,1-dimethylguanidine, PubChem CID:4091",

author = "Moheimani, \{Hamid Reza\} and Taghi Amiriani and Alizadeh, \{Ali Mohammad\} and Yahya Jand and Delaram Shakiba and Ensan, \{Parham Sayyah\} and Fatemeh Jafarzadeh and Maryam Rajaei and Ayesheh Enayati and Mona Pourabouk and Shahriar Aliazadeh and Pourkhani, \{Amir Hoshang\} and Zohreh Mazaheri and Zeyghami, \{Mohammad Ali\} and Ahmadreza Dehpour and Vahid Khori",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier B.V.",

year = "2021",

month = feb,

day = "15",

doi = "10.1016/j.ejphar.2020.173807",

language = "English (US)",

volume = "893",

journal = "European Journal of Pharmacology",

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TY - JOUR

T1 - Preconditioning and anti-apoptotic effects of Metformin and Cyclosporine-A in an isolated bile duct-ligated rat heart

AU - Moheimani, Hamid Reza

AU - Amiriani, Taghi

AU - Alizadeh, Ali Mohammad

AU - Jand, Yahya

AU - Shakiba, Delaram

AU - Ensan, Parham Sayyah

AU - Jafarzadeh, Fatemeh

AU - Rajaei, Maryam

AU - Enayati, Ayesheh

AU - Pourabouk, Mona

AU - Aliazadeh, Shahriar

AU - Pourkhani, Amir Hoshang

AU - Mazaheri, Zohreh

AU - Zeyghami, Mohammad Ali

AU - Dehpour, Ahmadreza

AU - Khori, Vahid

PY - 2021/2/15

Y1 - 2021/2/15

N2 - 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.

AB - 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.

KW - Bile duct ligation

KW - Caspase

KW - Cyclosporin-A

KW - Cyclosporin-A (3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-Ethyl-33-[(E,1R,2R)-1-Hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31undecazacyclotritriacontane-2

KW - Ischemic preconditioning

KW - Metformin

KW - Metformin 3-(diaminomethylidene)-1,1-dimethylguanidine, PubChem CID:4091

UR - https://www.scopus.com/pages/publications/85098876509

UR - https://www.scopus.com/pages/publications/85098876509#tab=citedBy

U2 - 10.1016/j.ejphar.2020.173807

DO - 10.1016/j.ejphar.2020.173807

M3 - Article

C2 - 33359222

AN - SCOPUS:85098876509

SN - 0014-2999

VL - 893

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

M1 - 173807

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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