Acute metformin treatment provides cardioprotection via improved mitochondrial function in cardiac ischemia / reperfusion injury

© 2020 The Author(s) Cardiac ischemia/reperfusion (I/R) injury following reperfusion therapy in acute myocardial infarction results in mitochondrial dynamic imbalance and cardiomyocyte apoptosis. Although diabetic patients taking metformin have been shown to have a lower risk of myocardial infarctio...

Full description

Saved in:
Bibliographic Details
Main Authors: Siripong Palee, Louis Higgins, Tom Leech, Siriporn C. Chattipakorn, Nipon Chattipakorn
Format: Journal
Published: 2020
Subjects:
Online Access:https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85089155725&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/71013
Tags: Add Tag
No Tags, Be the first to tag this record!
Institution: Chiang Mai University
id th-cmuir.6653943832-71013
record_format dspace
spelling th-cmuir.6653943832-710132020-10-14T08:47:01Z Acute metformin treatment provides cardioprotection via improved mitochondrial function in cardiac ischemia / reperfusion injury Siripong Palee Louis Higgins Tom Leech Siriporn C. Chattipakorn Nipon Chattipakorn Pharmacology, Toxicology and Pharmaceutics © 2020 The Author(s) Cardiac ischemia/reperfusion (I/R) injury following reperfusion therapy in acute myocardial infarction results in mitochondrial dynamic imbalance and cardiomyocyte apoptosis. Although diabetic patients taking metformin have been shown to have a lower risk of myocardial infarction, the efficacy of the cardioprotection conferred by metformin regarding the mitochondrial function and dynamic in cardiac I/R injury are still inconclusive. In addition, the comparative effects between different doses of metformin given acutely prior to cardiac I/R injury have never been investigated. Fifty 8-week-old male Wistar rats weighing 300−350 g were divided into sham-operated (n = 10) and cardiac I/R-operated (n = 40) groups. In the cardiac I/R group, rats underwent 30-min ischemia followed by 120-min reperfusion and were randomly divided into four subgroups (n = 10/group): control (received normal saline), metformin (100, 200, and 400 mg/kg). The arrhythmia score, cardiac function, infarct size, mortality rate, mitochondrial function and apoptosis, were determined. Metformin (200 mg/kg) exerted the highest level of cardioprotection through reduction in arrhythmia, infarct size, mitochondrial fission, and apoptosis, in addition to preservation of mitochondrial function, leading to the attenuation of cardiac dysfunction. Doses of metformin (100 and 400 mg/kg) also improved mitochondrial and cardiac function, but to a lesser extent than metformin (200 mg/kg). In conclusion, metformin exerts cardioprotection by attenuating mitochondrial dysfunction, mitochondrial dynamic imbalance, and apoptosis. These led to decreased infarct size and eventual improvement in cardiac function in rats with acute cardiac I/R injury. These findings indicate the potential clinical benefits of acute metformin treatment in acute myocardial infarction. 2020-10-14T08:47:01Z 2020-10-14T08:47:01Z 2020-10-01 Journal 19506007 07533322 2-s2.0-85089155725 10.1016/j.biopha.2020.110604 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85089155725&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/71013
institution Chiang Mai University
building Chiang Mai University Library
continent Asia
country Thailand
Thailand
content_provider Chiang Mai University Library
collection CMU Intellectual Repository
topic Pharmacology, Toxicology and Pharmaceutics
spellingShingle Pharmacology, Toxicology and Pharmaceutics
Siripong Palee
Louis Higgins
Tom Leech
Siriporn C. Chattipakorn
Nipon Chattipakorn
Acute metformin treatment provides cardioprotection via improved mitochondrial function in cardiac ischemia / reperfusion injury
description © 2020 The Author(s) Cardiac ischemia/reperfusion (I/R) injury following reperfusion therapy in acute myocardial infarction results in mitochondrial dynamic imbalance and cardiomyocyte apoptosis. Although diabetic patients taking metformin have been shown to have a lower risk of myocardial infarction, the efficacy of the cardioprotection conferred by metformin regarding the mitochondrial function and dynamic in cardiac I/R injury are still inconclusive. In addition, the comparative effects between different doses of metformin given acutely prior to cardiac I/R injury have never been investigated. Fifty 8-week-old male Wistar rats weighing 300−350 g were divided into sham-operated (n = 10) and cardiac I/R-operated (n = 40) groups. In the cardiac I/R group, rats underwent 30-min ischemia followed by 120-min reperfusion and were randomly divided into four subgroups (n = 10/group): control (received normal saline), metformin (100, 200, and 400 mg/kg). The arrhythmia score, cardiac function, infarct size, mortality rate, mitochondrial function and apoptosis, were determined. Metformin (200 mg/kg) exerted the highest level of cardioprotection through reduction in arrhythmia, infarct size, mitochondrial fission, and apoptosis, in addition to preservation of mitochondrial function, leading to the attenuation of cardiac dysfunction. Doses of metformin (100 and 400 mg/kg) also improved mitochondrial and cardiac function, but to a lesser extent than metformin (200 mg/kg). In conclusion, metformin exerts cardioprotection by attenuating mitochondrial dysfunction, mitochondrial dynamic imbalance, and apoptosis. These led to decreased infarct size and eventual improvement in cardiac function in rats with acute cardiac I/R injury. These findings indicate the potential clinical benefits of acute metformin treatment in acute myocardial infarction.
format Journal
author Siripong Palee
Louis Higgins
Tom Leech
Siriporn C. Chattipakorn
Nipon Chattipakorn
author_facet Siripong Palee
Louis Higgins
Tom Leech
Siriporn C. Chattipakorn
Nipon Chattipakorn
author_sort Siripong Palee
title Acute metformin treatment provides cardioprotection via improved mitochondrial function in cardiac ischemia / reperfusion injury
title_short Acute metformin treatment provides cardioprotection via improved mitochondrial function in cardiac ischemia / reperfusion injury
title_full Acute metformin treatment provides cardioprotection via improved mitochondrial function in cardiac ischemia / reperfusion injury
title_fullStr Acute metformin treatment provides cardioprotection via improved mitochondrial function in cardiac ischemia / reperfusion injury
title_full_unstemmed Acute metformin treatment provides cardioprotection via improved mitochondrial function in cardiac ischemia / reperfusion injury
title_sort acute metformin treatment provides cardioprotection via improved mitochondrial function in cardiac ischemia / reperfusion injury
publishDate 2020
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85089155725&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/71013
_version_ 1681753007485616128