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Updated: May 14, 2026
A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
[Blocking extracellular HMGB1 activity protects against doxorubicin induced cardiac injury in mice]
Yong-Gang Ma1, Xiao-Wei Zhang, Hua-Yan Bao
1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Abstract:
This study aims to investigate the preventive role and potential mechanisms of blocking extracellular HMGB1 function on doxorubicin induced cardiac injury. Mice were treated with HMGB1 blocker glycyrrhizin 1 h before and one time every day (intraperitoneal, 10 mg per mouse) after doxorubicin injection, and sacrificed on the day 14 after doxorubicin challenge. Cardiac function was evaluated by echocardiography and hemodynamic measurement. Myocardial inflammation and collagen deposition were analyzed by immunohistochemistry and picrosirius red staining. The interaction of HMGB1 and TLR2 was assessed by co-immunoprecipitation and confocal microscopy. The protein contents of HMGB1, MyD88, p65NF-kappaB and phospho-p65NF-kappaB were measured by Immunoblot. Compared with mice treated with saline, doxorubicin treatment led to an upregulation in HMGB1 expression. Blocking HMGB1 activity with glycyrrhizin protected mice against cardiac dysfunction, inflammatory response, and cardiac fibrosis induced by doxorubicin challenge. Glycyrrhizin inhibited the interaction of HMGB1 and TLR2, and blocked the downstream signaling of TLR2. In conclusion, blocking HMGB1 protected against doxorubicin induced cardiac injury by inhibiting TLR2 signaling pathway.
Insights
Blocking High Mobility Group Box 1 (HMGB1) with glycyrrhizin prevents doxorubicin-induced cardiac injury. This intervention protects heart function by inhibiting the HMGB1-TLR2 signaling pathway.
Area of Science:
- Cardiology
- Immunology
- Molecular Biology
Context:
- Doxorubicin is a widely used chemotherapy agent with known cardiotoxic side effects.
- Cardiac injury induced by doxorubicin involves inflammatory and fibrotic processes.
- High Mobility Group Box 1 (HMGB1) has been implicated in various inflammatory conditions, including cardiac damage.
Purpose:
- To investigate the protective effects of blocking extracellular HMGB1 on doxorubicin-induced cardiac injury.
- To elucidate the underlying mechanisms, focusing on the HMGB1-Toll-like receptor 2 (TLR2) signaling pathway.
Summary:
- Mice received glycyrrhizin, an HMGB1 blocker, before and after doxorubicin administration.
- Cardiac function, inflammation, and fibrosis were assessed. HMGB1 expression, HMGB1-TLR2 interaction, and downstream signaling molecules (MyD88, p65NF-kappaB) were analyzed.
- Glycyrrhizin treatment significantly improved cardiac function, reduced inflammation and fibrosis, and inhibited the HMGB1-TLR2 interaction and subsequent signaling.
Impact:
- Blocking HMGB1 with glycyrrhizin offers a potential therapeutic strategy to mitigate doxorubicin-induced cardiotoxicity.
- This study highlights the critical role of the HMGB1-TLR2 axis in chemotherapy-induced cardiac damage.
- Findings provide a mechanistic basis for developing novel cardioprotective agents targeting this pathway.
