PUBLICATION
Calycosin attenuates doxorubicin-induced cardiotoxicity via autophagy regulation in zebrafish models
- Authors
- Lu, X., Lu, L., Gao, L., Wang, Y., Wang, W.
- ID
- ZDB-PUB-210326-1
- Date
- 2021
- Source
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 137: 111375 (Journal)
- Registered Authors
- Keywords
- Autophagy, Calycosin, Cardiotoxicity, Doxorubicin, Zebrafish
- MeSH Terms
-
- Animals
- Antibiotics, Antineoplastic/toxicity*
- Autophagy/drug effects*
- Autophagy-Related Protein 7/drug effects
- Cardiotonic Agents/pharmacology*
- Cardiotoxicity*
- Doxorubicin/antagonists & inhibitors*
- Doxorubicin/toxicity*
- Embryo, Nonmammalian
- Heart/drug effects
- Heart Function Tests
- Isoflavones/pharmacology*
- Myocardium/pathology
- Survival Analysis
- Zebrafish*
- PubMed
- 33761601 Full text @ Biomed. Pharmacother.
Citation
Lu, X., Lu, L., Gao, L., Wang, Y., Wang, W. (2021) Calycosin attenuates doxorubicin-induced cardiotoxicity via autophagy regulation in zebrafish models. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 137:111375.
Abstract
Anthracyclines are highly effective chemotherapeutics for antineoplastic treatment. However, cumulative cardiotoxicity is the main side effect with poor prognosis. No mechanism-based therapy is currently available to reverse chronic anthracycline-induced cardiotoxicity (AIC) after the deterioration of cardiac function. Calycosin (CA) is the main compound extracted from the traditional Chinese medicine Astragalus, and it has diverse beneficial effects, including autophagy modulation, anti-inflammatory and anti-tumor effects. Autophagy dysregulation is an important pathological event in AIC. Our study demonstrated a cardioprotective effect of CA in a zebrafish embryonic AIC model. To assess the effect of CA on late-onset chronic AIC, adult zebrafish were treated with CA 28 days after doxorubicin (DOX) injection, at which point heart function was obviously impaired. The results demonstrated that DOX blocked autophagic activity in adult zebrafish 8 weeks post-injection, and CA treatment improved heart function and restored autophagy. Further in vitro experiments demonstrated that atg7, which encodes an E1-like activating enzyme, may play an essential role in the CA regulation of autophagy. In conclusion, we used a rapid pharmacological screening system in embryo-adult zebrafish in vivo and elucidated the mechanism of gene targeting in vitro.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping