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Therapeutic potentials of cell death inhibitors in rats with cardiac ischaemia/reperfusion injury.

Authors :
Luo Y
Apaijai N
Liao S
Maneechote C
Chunchai T
Arunsak B
Benjanuwattra J
Yanpiset P
Chattipakorn SC
Chattipakorn N
Source :
Journal of cellular and molecular medicine [J Cell Mol Med] 2022 Apr; Vol. 26 (8), pp. 2462-2476. Date of Electronic Publication: 2022 Mar 21.
Publication Year :
2022

Abstract

Growing evidence demonstrated that cell death pathways including ferroptosis, apoptosis and necroptosis contribute to cardiac ischaemia/reperfusion (I/R) injury. We hypothesized that ferroptosis, apoptosis and necroptosis contribute differently to myocardial damage during acute cardiac I/R injury. Rats underwent cardiac I/R or sham operation. I/R-operated rats were divided into 4 groups: vehicle, apoptosis (Z-vad), ferroptosis (Fer-1) and necroptosis (Nec-1) inhibition. Rats in each cell death inhibitor group were subdivided into 3 different dose regimens: low, medium and high. Infarct size, left ventricular (LV) function, arrhythmias and molecular mechanism were investigated. Cardiac I/R caused myocardial infarction, LV dysfunction, arrhythmias, mitochondrial dysfunction, mitochondrial dynamic imbalance, inflammation, apoptosis and ferroptosis. Infarct size, LV dysfunction, mitochondrial dysfunction, apoptosis and ferroptosis were all reduced to a similar extent in rats treated with Z-vad (low and medium doses) or Fer-1 (medium and high doses). Fer-1 treatment also reduced mitochondrial dynamic imbalance and inflammation. No evidence of necroptosis was found in association with acute I/R injury, therefore Nec-1 treatment could not be assessed. Apoptosis and ferroptosis, not necroptosis, contributed to myocardial damage in acute I/R injury. Inhibitors of these 2 pathways provided effective cardioprotection in rats with I/R injury though modulation of mitochondrial function and attenuated apoptosis and ferroptosis.<br /> (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Details

Language :
English
ISSN :
1582-4934
Volume :
26
Issue :
8
Database :
MEDLINE
Journal :
Journal of cellular and molecular medicine
Publication Type :
Academic Journal
Accession number :
35315192
Full Text :
https://doi.org/10.1111/jcmm.17275