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Updated: Sep 26, 2025
A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish
Published on: June 7, 2018
Spinacetin alleviates doxorubicin-induced cardiotoxicity by initiating protective autophagy through SIRT3/AMPK/mTOR
1Department of cardiovascular surgery, XiJing Hospital, The Fourth Military Medical University.
Background:
Doxorubicin-induced myocardiopathy is a massive obstacle in administering chemotherapeutic drugs in cancer patients.
Purposes:
In the present study, we aim to investigate the effects of spinacetin, a flavonoid glycoside, on doxorubicin-induced cardiotoxicity.
Study Design:
The doxorubicin-induced cardiotoxicity mice model was established to evaluate the cardioprotective effects of SP. The H9C2 cell line was used to study SP's potential mechanisms of action. Dexrazoxane (180 mg/kg) was used as the positive control.
Methods:
The CCK-8 cell proliferation assay, hematoxylin and eosin (HE) staining, detection of serum biomarkers, flow cytometry for apoptosis, dansylcadaverine (MDC) staining, and Western blot for crucial molecules were conducted in the present study.
Results:
SP significantly increased the survival rate of primary cardiomyocytes and decreased the serum LDH, CK-MB, TrT, and myocardial MDA level. The apoptosis of cardiomyocytes significantly decreased by SP, with upregulation of autophagy. In the H9C2 cell line, SP protects the cells from doxorubicin-induced cytotoxicity, decreases apoptosis, and increases autophagy. The subsequent mechanism study showed that the activation of AMPK/mTOR signaling was involved in the protective effects of SP on doxorubicin-induced cardiotoxicity through upregulating the expression level of SIRT3.
Conclusion:
We concluded that SP could protect against doxorubicin-induced cardiotoxicity both in vitro and in vivo by initiating protective autophagy through SIRT3/AMPK/mTOR pathways, which has not been reported previously. SP could be treated as a potential candidate for cardioprotective usage during chemotherapy. The further clinical study is still urgently needed to investigate the safety and effectiveness of SP in patients.
Insights
Spinacetin (SP) protects against doxorubicin-induced cardiotoxicity by promoting autophagy via the SIRT3/AMPK/mTOR pathway. This flavonoid glycoside shows potential as a cardioprotective agent during chemotherapy.
Area of Science:
- Cardiology
- Pharmacology
- Cell Biology
Background:
- Doxorubicin chemotherapy can cause cardiotoxicity, limiting its use in cancer patients.
- Identifying protective agents is crucial for improving cancer treatment outcomes.
Purpose of the Study:
- To investigate the cardioprotective effects of spinacetin (SP), a flavonoid glycoside, against doxorubicin-induced cardiotoxicity.
- To elucidate the underlying mechanisms of SP's protective actions.
Main Methods:
- Established a doxorubicin-induced cardiotoxicity mouse model and used the H9C2 cell line.
- Assessed cell viability, apoptosis, autophagy, serum biomarkers, and protein expression via Western blot.
- Utilized dexrazoxane as a positive control.
Main Results:
- SP significantly improved survival rates and reduced cardiac damage markers (LDH, CK-MB, TrT, MDA) in vivo.
- SP decreased cardiomyocyte apoptosis and enhanced autophagy in both in vitro and in vivo models.
- SP activated the SIRT3/AMPK/mTOR signaling pathway, upregulating SIRT3 expression.
Conclusions:
- Spinacetin demonstrates significant cardioprotective effects against doxorubicin-induced cardiotoxicity through autophagy induction via the SIRT3/AMPK/mTOR pathway.
- SP is a potential candidate for cardioprotection during chemotherapy, warranting further clinical investigation.
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