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Updated: Jun 10, 2026
A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
Doxycycline suppresses doxorubicin-induced oxidative stress and cellular apoptosis in mouse hearts
Hui-Chin Lai1, Yueh-Chiao Yeh, Chih-Tai Ting
1Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan.
Abstract:
Cardiac toxicity remains a serious yet unsolved complication of doxorubicin. This study was designed to examine whether doxycycline, a tetracycline-derived synthetic antibiotic with potential cytoprotective properties, could ameliorate this complication of doxorubicin. Male mice at 4-week of age were administrated with vehicle, doxorubicin (3mg/kg intraperitoneally every other day at 3 doses), doxycycline (2.5mg/kg intraperitoneally every other day for 3 doses), or doxycycline plus doxorubicin (each dose given 1day post doxycycline). After 28days, left ventricular geometric and systolic parameters were measured by transthoracic echocardiography, and hearts were harvested for extensive analyses regarding oxidative stress and cellular apoptosis. At 28days, hearts of doxorubicin-treated mice were characterized by less weight compared with controls, also with remodeling and depressed systolic function of the left ventricle. Biochemical analyses disclosed that content of malondialdehyde was increased and activity of antioxidant enzymes, including superoxide dismutase and glutathione peroxidase, was decreased in these hearts. Both mitochondrion-dependent and endoplasmic reticulum stress-induced apoptotic pathways were also activated in the hearts of doxorubicin-treated mice as reflected by decreased Bcl-2/Bcl-(XL) and elevated Bax/Bad, p53/Apaf-1, endoplasmic reticulum glucose-related protein 78, C/EBP homologous protein, cytochrome c release from mitochondria, caspases-9/-3 cleavage, and cardiomyocyte apoptosis. In contrast, all the above left ventricular remodeling, systolic depressing, oxidative and pro-apoptotic actions of doxorubicin could be significantly alleviated by doxycycline pretreatment. Thus, doxycycline extensively counteracts multiple oxidative and apoptotic actions of doxorubicin in heart, hence may serve as an adjuvant agent to assuage the untoward cardiac effects of doxorubicin in clinical application.
Insights
Doxycycline pretreatment significantly counteracts doxorubicin-induced cardiac toxicity in mice by reducing oxidative stress and apoptosis. This suggests doxycycline may serve as a protective adjuvant therapy against doxorubicin
Area of Science:
- Cardiology
- Pharmacology
- Toxicology
Background:
- Doxorubicin chemotherapy is associated with significant cardiac toxicity.
- This cardiotoxicity presents as left ventricular remodeling and impaired systolic function.
- Oxidative stress and apoptosis are key mechanisms underlying doxorubicin-induced heart damage.
Purpose of the Study:
- To investigate the potential cardioprotective effects of doxycycline against doxorubicin toxicity.
- To evaluate doxycycline's impact on doxorubicin-induced oxidative stress and apoptosis in the heart.
Main Methods:
- Male mice were treated with doxorubicin, doxycycline, or a combination.
- Cardiac function was assessed using transthoracic echocardiography.
- Heart tissues were analyzed for oxidative stress markers and apoptotic pathway activation.
Main Results:
- Doxorubicin treatment led to cardiac remodeling, reduced systolic function, increased malondialdehyde, and decreased antioxidant enzyme activity.
- Doxorubicin induced both mitochondrion-dependent and endoplasmic reticulum stress-mediated apoptosis.
- Doxycycline pretreatment significantly alleviated doxorubicin-induced cardiac dysfunction, oxidative stress, and apoptosis.
Conclusions:
- Doxycycline effectively counteracts doxorubicin's detrimental effects on the heart.
- Doxycycline demonstrates potential as an adjuvant agent to mitigate doxorubicin cardiotoxicity in clinical settings.
