# Thymidine exerts anti-doxorubicin-induced cardiomyopathy effect through the regulation of the PPAR signaling pathways and ferroptosis pathways

## TL;DR

Thymidine helps protect the heart from doxorubicin damage by affecting specific genetic pathways linked to heart function and cell death.

## Contribution

This study reveals thymidine's novel protective mechanism against doxorubicin-induced heart damage via PPAR and ferroptosis pathways.

## Key findings

- Thymidine reversed doxorubicin-induced heart function impairments in zebrafish.
- Thymidine regulated genes in PPAR and ferroptosis pathways linked to heart protection.
- Thymidine reduced pericardial edema and pathological changes in heart tissue.

## Abstract

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 DOX-induced cardiomyopathy. The regulatory roles of key genes in the pathways associated with the cardioprotective activity of Thy were analyzed via 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 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.

Diagram exploring methods to counteract doxorubicin-induced cardiotoxicity during cancer treatment, highlighting affected organs like lungs and liver. It involves zebrafish studies, showcasing morphological changes over days post-fertilization, and gene expression analysis done via specialized equipment with accompanying charts. Doxorubicin and thymine chemical structures are displayed.