PUBLICATION
Paeonol Reverses Adriamycin Induced Cardiac Pathological Remodeling through Notch1 Signaling Reactivation in H9c2 Cells and Adult Zebrafish Heart
- Authors
- Thabassum Akhtar Iqbal, S., Tirupathi Pichiah, P.B., Raja, S., Arunachalam, S.
- ID
- ZDB-PUB-190717-1
- Date
- 2019
- Source
- Chemical Research in Toxicology 33(2): 312-323 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Acetophenones/pharmacology*
- Animals
- Cell Survival/drug effects
- Cells, Cultured
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Doxorubicin/antagonists & inhibitors*
- Doxorubicin/toxicity*
- Heart/drug effects*
- Myocytes, Cardiac/drug effects*
- Myocytes, Cardiac/metabolism
- Myocytes, Cardiac/pathology
- Rats
- Receptor, Notch1/antagonists & inhibitors
- Receptor, Notch1/genetics
- Receptor, Notch1/metabolism*
- Signal Transduction/drug effects
- Structure-Activity Relationship
- Zebrafish/metabolism*
- PubMed
- 31307187 Full text @ Chem. Res. Toxicol.
- CTD
- 31307187
Citation
Thabassum Akhtar Iqbal, S., Tirupathi Pichiah, P.B., Raja, S., Arunachalam, S. (2019) Paeonol Reverses Adriamycin Induced Cardiac Pathological Remodeling through Notch1 Signaling Reactivation in H9c2 Cells and Adult Zebrafish Heart. Chemical Research in Toxicology. 33(2):312-323.
Abstract
Adriamycin is a commonly prescribed chemotherapeutic drug for a wide range of cancers. Adriamycin causes cardiotoxicity as an adverse effect that limits its clinical application in cancer treatment. Several mechanisms have been proposed to explain the toxicity it causes in heart cells. Disruption of inherent cardiac repair mechanism is the least understood mechanism of Adriamycin-induced cardiotoxicity. Adriamycin induces pathological remodeling in cardiac cells by promoting apoptosis, hypertrophy and fibrosis. We found that Adriamycin inhibited Notch1 in a time and dose dependent manner in H9c2 cells. We used Paeonol, a Notch1 activator and analyzed the markers of apoptosis, hypertrophy and fibrosis in H9c2 cells in vitro and in adult zebrafish heart in vivo as model system to study Adriamycin induced cardiotoxicity. Paeonol activated Notch1 signaling and expression of its downstream target genes effectively in the Adriamycin treated condition invitro and in vivo. Also we detected that Notch activation using Paeonol protected the cells from apoptosis, collagen deposition and hypertrophy response using functional assays. We conclude that Adriamycin induced cardiotoxicity by promoting the pathological cardiac remodeling through inhibition of Notch1 signaling and that the Notch1 reactivation by Paeonol protected the cells and reversed the cardiotoxicity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping