Caffeic Acid Phenethyl Ester Protects Against Doxorubicin-Induced Cardiotoxicity via Inhibiting the ROS-MLKL-Mediated Cross-Talk Between Oxidative Stress and Necroptosis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Reagents and Chemicals
2.2. Cell Lines and Culture
2.3. Animals and Treatments
2.4. Cell Viability Assay
2.5. Surface Electrocardiogram (ECG) Assessment of Cardiac Function
2.6. Histopathologic Assay
2.7. Measurement of Serum Levels of cTn-I, CK-MB and LDH
2.8. Transmission Electron Microscopy (TEM)
2.9. Oxidative Stress Detection
2.10. Mitochondrial Respiration Analysis
2.11. Western Blotting
2.12. Immunohistochemistry Assay (IHC)
2.13. Plasmid Transfection
2.14. Statistical Analysis
3. Results
3.1. CAPE Alleviated DOX-Induced Myocardial Injury In Vivo
3.2. CAPE Alleviated DOX-Induced Myocardial Injury In Vitro
3.3. CAPE Attenuated DOX-Induced Oxidative Stress
3.4. CAPE Inhibited DOX-Induced Necroptosis by Inhibiting the RIPK1/RIPK3/MLKL Pathway
3.5. The Cross-Talk Between Oxidative Stress and Necroptosis Played a Vital Role in DOX-Induced Cardiotoxicity
3.6. CAPE-Inhibited ROS-MLKL Signaling Mediated the Cross-Talk Between Oxidative Stress and Necroptosis
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Jiang, C.; Zhang, T.; Gu, J.; Shen, C.; Gao, H.; An, H.; Wang, C.; Lu, J.; Lin, S.; Zhao, H.; et al. Caffeic Acid Phenethyl Ester Protects Against Doxorubicin-Induced Cardiotoxicity via Inhibiting the ROS-MLKL-Mediated Cross-Talk Between Oxidative Stress and Necroptosis. Biomolecules 2025, 15, 783. https://doi.org/10.3390/biom15060783
Jiang C, Zhang T, Gu J, Shen C, Gao H, An H, Wang C, Lu J, Lin S, Zhao H, et al. Caffeic Acid Phenethyl Ester Protects Against Doxorubicin-Induced Cardiotoxicity via Inhibiting the ROS-MLKL-Mediated Cross-Talk Between Oxidative Stress and Necroptosis. Biomolecules. 2025; 15(6):783. https://doi.org/10.3390/biom15060783
Chicago/Turabian StyleJiang, Chenying, Tinghuang Zhang, Jiawen Gu, Chenjun Shen, Hang Gao, Hai An, Chen Wang, Jiahui Lu, Shengzhang Lin, Huajun Zhao, and et al. 2025. "Caffeic Acid Phenethyl Ester Protects Against Doxorubicin-Induced Cardiotoxicity via Inhibiting the ROS-MLKL-Mediated Cross-Talk Between Oxidative Stress and Necroptosis" Biomolecules 15, no. 6: 783. https://doi.org/10.3390/biom15060783
APA StyleJiang, C., Zhang, T., Gu, J., Shen, C., Gao, H., An, H., Wang, C., Lu, J., Lin, S., Zhao, H., & Zhu, Z. (2025). Caffeic Acid Phenethyl Ester Protects Against Doxorubicin-Induced Cardiotoxicity via Inhibiting the ROS-MLKL-Mediated Cross-Talk Between Oxidative Stress and Necroptosis. Biomolecules, 15(6), 783. https://doi.org/10.3390/biom15060783