Fisetin protects against cardiac cell death through reduction of ROS production  and caspases activity.

Flavonoids; Flavonols; Reactive Oxygen Species; EC 3.4.22.- (Caspases); OO2ABO9578 (fisetin); S88TT14065 (Oxygen); Animals; Animals, Newborn; Caspases/metabolism; Cell Death/drug effects; Cell Hypoxia/drug effects; Cell Line; Cell Proliferation/drug effects; Cytoprotection/drug effects; DNA Damage; Drug Evaluation, Preclinical; Enzyme Activation/drug effects; Flavonoids/pharmacology; Gene Expression Regulation/drug effects; Models, Biological; Myocardium/enzymology/pathology; Myocytes, Cardiac/drug effects; Oxygen; Rats; Reactive Oxygen Species/metabolism

Abstract :

[en] Myocardial infarction (MI) is a leading cause of death worldwide. Reperfusion is considered as an optimal therapy following cardiac ischemia. However, the promotion of a rapid elevation of O(2) levels in ischemic cells produces high amounts of reactive oxygen species (ROS) leading to myocardial tissue injury. This phenomenon is called ischemia reperfusion injury (IRI). We aimed at identifying new and effective compounds to treat MI and minimize IRI. We previously studied heart regeneration following myocardial injury in zebrafish and described each step of the regeneration process, from the day of injury until complete recovery, in terms of transcriptional responses. Here, we mined the data and performed a deep in silico analysis to identify drugs highly likely to induce cardiac regeneration. Fisetin was identified as the top candidate. We validated its effects in an in vitro model of MI/IRI in mammalian cardiac cells. Fisetin enhances viability of rat cardiomyocytes following hypoxia/starvation - reoxygenation. It inhibits apoptosis, decreases ROS generation and caspase activation and protects from DNA damage. Interestingly, fisetin also activates genes involved in cell proliferation. Fisetin is thus a highly promising candidate drug with clinical potential to protect from ischemic damage following MI and to overcome IRI.

Disciplines :

Oncology

Author, co-author :

Rodius, Sophie; Quantitative Biology Unit, Luxembourg Institute of Health (LIH), Luxembourg, 1445, Strassen, Luxembourg. sophie.rodius@lih.lu.

de Klein, Niek; Department of Genetics, University of Groningen, Groningen, 9700 RB, The Netherlands. ; The author completed this work at the Department of Oncology, Luxembourg Institute of Health (LIH), Luxembourg, 1445, Strassen, Luxembourg.

Jeanty, Céline; Quantitative Biology Unit, Luxembourg Institute of Health (LIH), Luxembourg, 1445, Strassen, Luxembourg.

Sánchez-Iranzo, Héctor ; Development of the Epicardium and Its Role During Regeneration Group, Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029, Madrid, Spain.

Crespo, Isaac; Vital-IT Systems Biology Division, SIB Swiss Institute of Bioinformatics, Lausanne, CH-1015, Switzerland.

Ibberson, Mark; Vital-IT Systems Biology Division, SIB Swiss Institute of Bioinformatics, Lausanne, CH-1015, Switzerland.

Xenarios, Ioannis ; Vital-IT Systems Biology Division, SIB Swiss Institute of Bioinformatics, Lausanne, CH-1015, Switzerland. ; Center for Integrative Genomics, University of Lausanne, Lausanne, CH-1015, Switzerland. ; Department of Biochemistry, University of Geneva, 1211, Geneva, Switzerland.

DITTMAR, Gunnar ; Quantitative Biology Unit, Luxembourg Institute of Health (LIH), Luxembourg, 1445, Strassen, Luxembourg.

Mercader, Nadia ; Development of the Epicardium and Its Role During Regeneration Group, Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029, Madrid, Spain. ; Institute of Anatomy, University of Bern, Bern, Switzerland.

NICLOU, Simone P. ; Department of Oncology, Luxembourg Institute of Health (LIH), Luxembourg, 1445, Strassen, Luxembourg.

AZUAJE, Francisco ; Quantitative Biology Unit, Luxembourg Institute of Health (LIH), Luxembourg, 1445, Strassen, Luxembourg. Francisco.Azuaje@ucb.com. ; Current affiliation: Data and Translational Sciences, UCB Celltech, 208 Bath Road, Slough, SL1 3WE, United Kingdom. Francisco.Azuaje@ucb.com.

External co-authors :

yes

Language :

English

Title :

Fisetin protects against cardiac cell death through reduction of ROS production and caspases activity.

Publication date :

19 February 2020

Journal title :

Scientific Reports

eISSN :

2045-2322

Publisher :

Nature Publishing Group, London, United Kingdom

Volume :

Issue :

Pages :

2896

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBilu :

since 26 February 2024

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