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

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

[img]
Preview
Text
s41598-020-59894-4-1.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (2MB) | Preview

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)

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:

13 Dec 2020 02:50

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

Actions (login required)

Edit item Edit item
Provide Feedback