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Purpose <p>The use of doxorubicin (DOX), a potent chemotherapy drug, is limited by its detrimental effects on the heart. This cardiotoxicity is primarily driven by oxidative stress and inflammation. TRIM35 plays a key role in inflammatory responses; however, its exact function in DOX-induced cardiotoxicity (DIC) remains to be fully understood. This study investigates the effects of TRIM35 on DIC and explores the underlying biological mechanisms.</p> Methods <p>To assess the role of TRIM35, we reduced the expression of TRIM35 in the heart tissues of mice using an adeno-associated virus 9 (AAV9) system, delivered through tail vein injection. We then administered weekly doses of DOX (4&#xa0;mg/kg) to C57BL/6 mice for 4 weeks to induce DIC. Echocardiography, histopathological assessments, and molecular techniques were employed to examine the effects and mechanisms of TRIM35 on DIC.</p> Results <p>Our research found that DOX treatment increases TRIM35 levels in the heart. By lowering TRIM35 expression, we observed an improvement in cardiac function and a decrease in myocardial damage in DOX-treated mice. Additionally, reduced TRIM35 expression lessened myocardial hypertrophy and fibrosis. It also mitigated the oxidative stress and inflammation caused by DOX. Furthermore, the down-regulation of TRIM35 expression resulted in the downregulation of TLR4 and phosphorylated P65 expression.</p> Conclusion <p>Downregulated TRIM35 expression mitigates the oxidative stress and inflammation caused by DOX, likely through impacting the TLR4/NF-κB signaling pathway. These insights indicate that TRIM35 holds promise as a therapeutic target for managing heart damage induced by DOX.</p>

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Downregulated TRIM35 Alleviates Doxorubicin-Induced Cardiotoxicity by Suppressing Oxidative Stress and Inflammation via Inhibiting TLR4/NF-κB Pathway

  • 期刊论文

  • 发表日期：

    2025年2月15日

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  • Yewen Hu,
  • Shiqi Wang,
  • Chaoxia Zhang,
  • Fuwei He,
  • Yongxing Jiang,
  • Ruoyu Chen,
  • Jia Su,
  • Caijie Shen,
  • Xiaomin Chen,
  • Huimin Chu

摘要

Purpose

The use of doxorubicin (DOX), a potent chemotherapy drug, is limited by its detrimental effects on the heart. This cardiotoxicity is primarily driven by oxidative stress and inflammation. TRIM35 plays a key role in inflammatory responses; however, its exact function in DOX-induced cardiotoxicity (DIC) remains to be fully understood. This study investigates the effects of TRIM35 on DIC and explores the underlying biological mechanisms.

Methods

To assess the role of TRIM35, we reduced the expression of TRIM35 in the heart tissues of mice using an adeno-associated virus 9 (AAV9) system, delivered through tail vein injection. We then administered weekly doses of DOX (4 mg/kg) to C57BL/6 mice for 4 weeks to induce DIC. Echocardiography, histopathological assessments, and molecular techniques were employed to examine the effects and mechanisms of TRIM35 on DIC.

Results

Our research found that DOX treatment increases TRIM35 levels in the heart. By lowering TRIM35 expression, we observed an improvement in cardiac function and a decrease in myocardial damage in DOX-treated mice. Additionally, reduced TRIM35 expression lessened myocardial hypertrophy and fibrosis. It also mitigated the oxidative stress and inflammation caused by DOX. Furthermore, the down-regulation of TRIM35 expression resulted in the downregulation of TLR4 and phosphorylated P65 expression.

Conclusion

Downregulated TRIM35 expression mitigates the oxidative stress and inflammation caused by DOX, likely through impacting the TLR4/NF-κB signaling pathway. These insights indicate that TRIM35 holds promise as a therapeutic target for managing heart damage induced by DOX.