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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Cardiovascular and Smooth Muscle Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1524167
This article is part of the Research Topic Innovative Approaches and Molecular Mechanisms in Cardiovascular Pharmacology View all 6 articles
Thymidine exerts anti-doxorubicin-induced cardiomyopathy effect through the regulation of the PPAR signaling pathways and ferroptosis pathways
Provisionally accepted- 1 Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
- 2 Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Jinan, Shandong Province, China
To evaluate the anti-cardiomyopathic activity of thymine (Thy) and to elucidate its mechanism of action. Transgenic zebrafish with enhanced green fluorescent protein (EGFP)-labelled hearts (Tg (cmlc2: EGFP)) and wild-type AB zebrafish were used as experimental animals. A blank control group, a doxorubicin (DOX) model group, a dexrazoxane (DEX)-positive drug group and Thy drug treatment group were established. After treatment, indicators closely related to cardiac function, such as the pericardial area, heart rate, stroke volume, short-axis shortening (SAS) rate, and ejection fraction of the zebrafish in each group, were evaluated to determine the protective activity of Thy against DOXinduced cardiomyopathy. The pathways involved in the cardioprotective activity of Thy were analyzed via transcriptomics, and the regulatory effects of Thy on key genes were investigated using RT-qPCR. The results indicated that Thy effectively relieved DOX-induced pericardial edema; reversed the effects of DOX on heart rate, stroke volume, SAS rate, ejection fraction, and blood flow velocity; and relieved DOX-induced myocardial ischemia, myocardial cell apoptosis and pathological structural changes in heart tissues. The transcriptome results indicated that the PPAR signaling and ferroptosis pathways were involved in the anti-DOX-induced cardiomyopathy effect of Thy. The RT-qPCR results revealed that Thy regulated the mRNA expression levels of genes related to the PPAR signaling pathway and ferroptosis pathway (such as pparg, apoa1a, acsl5, pltp, and tfa). Thy may exert its anti-DOX-induced cardiomyopathy effect through the regulation of the PPAR signaling and ferroptosis pathways.
Keywords: Thymidine, Doxorubicin, cardiomyopathy, Zebrafish, PPAR signaling pathway, Ferroptosis pathway
Received: 07 Nov 2024; Accepted: 05 Mar 2025.
Copyright: © 2025 Li, Wang, Zhou, Peihai, Sun, Xia and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yun Zhang, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
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