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Fisetin Confers Cardioprotection against Myocardial Ischemia Reperfusion Injury by Suppressing Mitochondrial Oxidative Stress and Mitochondrial Dysfunction and Inhibiting Glycogen Synthase Kinase 3β Activity
Joint Authors
Mohanraj, Rajesh
Kurian, Gino A.
Shanmugam, Karthi
Ravindran, Sriram
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-02-25
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Abstract EN
Acute myocardial infarction (AMI) is the leading cause of morbidity and mortality worldwide.
Timely reperfusion is considered an optimal treatment for AMI.
Paradoxically, the procedure of reperfusion can itself cause myocardial tissue injury.
Therefore, a strategy to minimize the reperfusion-induced myocardial tissue injury is vital for salvaging the healthy myocardium.
Herein, we investigated the cardioprotective effects of fisetin, a natural flavonoid, against ischemia/reperfusion (I/R) injury (IRI) using a Langendorff isolated heart perfusion system.
I/R produced significant myocardial tissue injury, which was characterized by elevated levels of lactate dehydrogenase and creatine kinase in the perfusate and decreased indices of hemodynamic parameters.
Furthermore, I/R resulted in elevated oxidative stress, uncoupling of the mitochondrial electron transport chain, increased mitochondrial swelling, a decrease of the mitochondrial membrane potential, and induction of apoptosis.
Moreover, IRI was associated with a loss of the mitochondrial structure and decreased mitochondrial biogenesis.
However, when the animals were pretreated with fisetin, it significantly attenuated the I/R-induced myocardial tissue injury, blunted the oxidative stress, and restored the structure and function of mitochondria.
Mechanistically, the fisetin effects were found to be mediated via inhibition of glycogen synthase kinase 3β (GSK3β), which was confirmed by a biochemical assay and molecular docking studies.
American Psychological Association (APA)
Shanmugam, Karthi& Ravindran, Sriram& Kurian, Gino A.& Mohanraj, Rajesh. 2018. Fisetin Confers Cardioprotection against Myocardial Ischemia Reperfusion Injury by Suppressing Mitochondrial Oxidative Stress and Mitochondrial Dysfunction and Inhibiting Glycogen Synthase Kinase 3β Activity. Oxidative Medicine and Cellular Longevity،Vol. 2018, no. 2018, pp.1-16.
https://search.emarefa.net/detail/BIM-1212362
Modern Language Association (MLA)
Shanmugam, Karthi…[et al.]. Fisetin Confers Cardioprotection against Myocardial Ischemia Reperfusion Injury by Suppressing Mitochondrial Oxidative Stress and Mitochondrial Dysfunction and Inhibiting Glycogen Synthase Kinase 3β Activity. Oxidative Medicine and Cellular Longevity No. 2018 (2018), pp.1-16.
https://search.emarefa.net/detail/BIM-1212362
American Medical Association (AMA)
Shanmugam, Karthi& Ravindran, Sriram& Kurian, Gino A.& Mohanraj, Rajesh. Fisetin Confers Cardioprotection against Myocardial Ischemia Reperfusion Injury by Suppressing Mitochondrial Oxidative Stress and Mitochondrial Dysfunction and Inhibiting Glycogen Synthase Kinase 3β Activity. Oxidative Medicine and Cellular Longevity. 2018. Vol. 2018, no. 2018, pp.1-16.
https://search.emarefa.net/detail/BIM-1212362
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1212362