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Doxycycline suppresses doxorubicin-induced oxidative stress and cellular apoptosis in mouse hearts
- Source :
- European journal of pharmacology. 644(1-3)
- Publication Year :
- 2009
-
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 (3 mg/kg intraperitoneally every other day at 3 doses), doxycycline (2.5 mg/kg intraperitoneally every other day for 3 doses), or doxycycline plus doxorubicin (each dose given 1 day post doxycycline). After 28 days, 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 28 days, 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.
- Subjects :
- Male
medicine.medical_specialty
Apoptosis
Biology
medicine.disease_cause
Endoplasmic Reticulum
Antioxidants
Mitochondria, Heart
chemistry.chemical_compound
Mice
Internal medicine
Malondialdehyde
medicine
Animals
Doxorubicin
Ventricular remodeling
Antibacterial agent
Pharmacology
Doxycycline
chemistry.chemical_classification
Glutathione Peroxidase
Mice, Inbred ICR
Antibiotics, Antineoplastic
Ventricular Remodeling
Superoxide Dismutase
Glutathione peroxidase
medicine.disease
Oxidative Stress
Endocrinology
chemistry
Oxidative stress
medicine.drug
Subjects
Details
- ISSN :
- 18790712
- Volume :
- 644
- Issue :
- 1-3
- Database :
- OpenAIRE
- Journal :
- European journal of pharmacology
- Accession number :
- edsair.doi.dedup.....8bed8ea369f0e1cf870e309626ee0836