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Updated: Mar 27, 2026
A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
Inflammatory mediators in a short-time mouse model of doxorubicin-induced cardiotoxicity
Michela Pecoraro1, Mariagiovanna Del Pizzo1, Stefania Marzocco1
1Department of Pharmacy, University of Salerno, Fisciano, SA, Italy.
Abstract:
Doxorubicin (DOXO) is commonly used to treat a wide range of malignant tumors, but its clinical use is limited by acute and chronic cardiotoxicity. The precise mechanism underlying DOXO-induced cardiotoxicity is still not completely elucidated, but cardiac inflammation seems to be involved. Effects of DOXO on proinflammatory cytokines, inflammatory cell infiltration, and necrosis have been proven only when a functional impairment has already occurred, so this study aimed to investigate the acute effect of DOXO administration in mouse heart. The results of our study demonstrated alterations in cardiac function parameters assessed by ultrasound within 24h after a single injection of DOXO, with a cumulative effect along the increase of the dose and the number of DOXO administrations. At the same time, DOXO causes a significant production of proinflammatory cytokines (such as TNF-α and IL-6) with a concomitant reduction of IL-10, a well-known antiinflammatory cytokine. Furthermore, overexpression of inducible nitric oxide synthase (iNOS) in heart tissue and increased levels of serum nitrite in DOXO-treated mice were detected. Notably, DOXO administration significantly increased nitrotyrosine expression in mouse heart. Our data support the hypothesis that these early events, could be responsible for the later onset of more severe deleterious remodeling leading to DOXO induced cardiomyopathy.
Insights
Doxorubicin (DOXO) causes early cardiac dysfunction and inflammation within 24 hours in mice. These findings reveal crucial insights into the mechanisms of DOXO-induced cardiotoxicity, highlighting the role of inflammation in heart damage.
Area of Science:
- Cardiology
- Oncology
- Toxicology
Background:
- Doxorubicin (DOXO) is a vital chemotherapy agent but causes significant cardiotoxicity.
- The exact mechanisms of DOXO-induced cardiotoxicity, particularly early inflammatory events, remain unclear.
- Existing research often links DOXO effects to established functional impairment.
Purpose of the Study:
- To investigate the acute effects of Doxorubicin administration on the mouse heart.
- To explore the early inflammatory responses and cardiac function alterations following DOXO treatment.
- To elucidate the initial molecular events contributing to DOXO-induced cardiotoxicity.
Main Methods:
- Single injection of Doxorubicin (DOXO) in mice.
- Cardiac function assessment using ultrasound within 24 hours.
- Measurement of proinflammatory cytokines (TNF-α, IL-6, IL-10), inducible nitric oxide synthase (iNOS), nitrite, and nitrotyrosine expression.
Main Results:
- DOXO induced significant alterations in cardiac function parameters within 24 hours post-injection.
- A dose-dependent and cumulative effect of DOXO on cardiac function was observed.
- DOXO administration led to increased production of TNF-α and IL-6, decreased IL-10, elevated iNOS and nitrite levels, and increased nitrotyrosine expression in the heart.
Conclusions:
- Early cardiac inflammation and oxidative stress are key events following acute DOXO administration.
- These initial inflammatory changes, including cytokine imbalance and iNOS/nitrotyrosine upregulation, may initiate the cascade leading to DOXO-induced cardiomyopathy.
- Understanding these early mechanisms is critical for developing strategies to mitigate DOXO cardiotoxicity.
