TY - JOUR
T1 - Fisetin protects against cardiac cell death through reduction of ROS production and caspases activity
AU - Rodius, Sophie
AU - de Klein, Niek
AU - Jeanty, Céline
AU - Sánchez-Iranzo, Héctor
AU - Crespo, Isaac
AU - Ibberson, Mark
AU - Xenarios, Ioannis
AU - Dittmar, Gunnar
AU - Mercader, Nadia
AU - Niclou, Simone P.
AU - Azuaje, Francisco
N1 - Funding Information:
We thank C. Guerin and L. Guyonnet for technical support in flow cytometry; PV. Nazarov, A. Muller, T. Kaoma and SY. Kim for statistical and informatics support. This work was supported by FNR, the Luxembourg National Research Fund, FNR-CORE INFUSED project. At the NorLux Laboratory and the Proteome and Genome Research Unit of LIH, it was also supported by funding from Luxembourg’s Ministry of Higher Education and Research (MESR).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85079792196
U2 - 10.1038/s41598-020-59894-4
DO - 10.1038/s41598-020-59894-4
M3 - Article
C2 - 32076073
AN - SCOPUS:85079792196
SN - 2045-2322
VL - 10
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 2896
ER -