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327645

METFORMIN AND CARVEDILOL AMELIORATE ISOPRENALINE-INDUCED MYOCARDIAL INFARCTION IN NON-DIABETIC RATS THROUGH AMPK ACTIVATION AND SUPPRESSION OF APOPTOSIS

Article

Last updated: 25 Dec 2024

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Abstract

The objective of this study was to clarify the ameliorative effect of metformin (MET), carvedilol (CAR), and their combination and the underlying mechanisms in a non-diabetic rat model of isoprenaline (ISO)-induced MI. The adult male Wistar rats were allocated into six groups (n=8). Control group A received saline while control group B received DMSO 0.5% (i.p) for 10 days. ISO-treated group: received ISO (85 mg/kg.i.p.) on the first and second day of the experiment with the injection of normal saline for 10 days from the first day. ISO+MET and ISO+CAR-treated groups: received ISO as previously described and MET (200 mg/kg.i.p.) and CAR (10 mg/kg.i.p.) respectively for 10 days from the first day of the experiment. ISO+MET+CAR-treated group: received ISO, MET, and CAR as previously described. In the ISO group, the rise in serum cardiac biomarkers cTn-I and LDH provided evidence of MI. In addition, cardiac MDA, IL6, caspase-3, and Bax gene levels were significantly elevated, while cardiac SOD, GSH, pAMPK, eNOS, Bcl-2 gene, and Bcl-2/Bax ratio levels were significantly reduced with histopathological changes in cardiac tissue. Whereas posttreatment with MET, CAR, and their combination significantly reversed these overwhelming ISO-induced damaging effects on the heart. In conclusion, MET, CAR, and their combination could improve myocardial injury in ISO-induced MI through AMPK signaling pathway activation, and anti-apoptotic, anti-inflammatory, and antioxidant mechanisms. Subsequently, promote the recovery of cardiomyocyte function.

DOI

10.21608/bfsa.2023.327645

Keywords

Metformin, Carvedilol, myocardial infarction, AMPK, apoptosis, Gene expression

Authors

First Name

Eman

Last Name

Ali

MiddleName

Mohammed

Affiliation

Department of Clinical pharmacology, Faculty of Medicine, Sohag University

Email

emanmohamed@med.sohag.edu.eg

City

Sohag

Orcid

-

First Name

Azza

Last Name

Abouelella

MiddleName

MA.

Affiliation

Department of Clinical Pharmacology, Faculty of Medicine, Sohag University, Egypt

Email

azza_mallak@yahoo.com

City

-

Orcid

-

Volume

46

Article Issue

2

Related Issue

44483

Issue Date

2023-12-01

Receive Date

2023-04-30

Publish Date

2023-12-01

Page Start

1,377

Page End

1,395

Print ISSN

1110-0052

Online ISSN

3009-7703

Article File

BFSA_Volume 46_Issue 2_Pages 1377-1395.pdf

PDF . 1.7MB

Link

https://bpsa.journals.ekb.eg/article_327645.html

Detail API

https://bpsa.journals.ekb.eg/service?article_code=327645

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327,645

Type

Original Article

Type Code

1,096

Publication Type

Journal

Publication Title

Bulletin of Pharmaceutical Sciences Assiut University

Publication Link

https://bpsa.journals.ekb.eg/

MainTitle

METFORMIN AND CARVEDILOL AMELIORATE ISOPRENALINE-INDUCED MYOCARDIAL INFARCTION IN NON-DIABETIC RATS THROUGH AMPK ACTIVATION AND SUPPRESSION OF APOPTOSIS

Details

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Article

Created At

25 Dec 2024