Rodius, Sophie; de Klein, Niek; Jeanty, Céline; Sánchez-Iranzo, Héctor; Crespo, Isaac; Ibberson, Mark; Xenarios, Ioannis; Dittmar, Gunnar; Mercader, Nadia; Niclou, Simone P; Azuaje, Francisco (2020). Fisetin protects against cardiac cell death through reduction of ROS production and caspases activity. Scientific reports, 10(1), p. 2896. Springer Nature 10.1038/s41598-020-59894-4
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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 O2 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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy 04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Functional Anatomy |
UniBE Contributor: |
Mercader Huber, Nadia Isabel |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2045-2322 |
Publisher: |
Springer Nature |
Language: |
English |
Submitter: |
Nadia Isabel Mercader Huber |
Date Deposited: |
10 Dec 2020 17:06 |
Last Modified: |
05 Dec 2022 15:41 |
Publisher DOI: |
10.1038/s41598-020-59894-4 |
PubMed ID: |
32076073 |
BORIS DOI: |
10.7892/boris.147041 |
URI: |
https://boris.unibe.ch/id/eprint/147041 |
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