ArticleActa pharmacologica Sinica2012
Chronic cardiotoxicity of doxorubicin involves activation of myocardial and circulating matrix metalloproteinases in rats.
Article in Acta pharmacologica Sinica, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Extracellular matrix remodeling in animal models of anthracycline-induced cardiomyopathy: a meta-analysis.Journal of molecular medicine (Berlin, Germany) · 2021Pooled it
- Effect of High Intensity Interval Training on Matrix Metalloproteinases in Women with Breast Cancer Receiving Anthracycline-Based Chemotherapy.Scientific reports · 2020Trial
- Temporal Dynamics of Extracellular Matrix Remodeling in Anthracycline-Induced Cardiotoxicity.Cells · 2025Review
- Telomere Length of Cardiomyocytes in Wistar Rat Treated with Doxorubicin: In Vivo Experimental Study.Bulletin of experimental biology and medicine · 2025Article
- The cardio-oncologic burden of breast cancer: molecular mechanisms and importance of preclinical models.Basic research in cardiology · 2025Review
- Mitigating Doxorubicin-Induced Cardiotoxicity through Quercetin Intervention: An Experimental Study in Rats.Antioxidants (Basel, Switzerland) · 2024Article
- The treatment with trandolapril and losartan attenuates pressure and volume overload alternations of cardiac connexin-43 and extracellular matrix in Ren-2 transgenic rats.Scientific reports · 2023Article
- Impact of Cerium Oxide Nanoparticles on Metabolic, Apoptotic, Autophagic and Antioxidant Changes in Doxorubicin-Induced Cardiomyopathy: Possible Underlying Mechanisms.Reports of biochemistry & molecular biology · 2023Article
- Genome-Wide Association Study IdentifiesJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Article
- Review
- Modeling Doxorubicin-Induced Cardiomyopathy With Fibrotic Myocardial Damage in Wistar Rats.Cardiology research · 2022Article
- Cardiac Remodelling Following Cancer Therapy: A Review.Cardiovascular toxicology · 2022Review
- Investigation of the Antiremodeling Effects of Losartan, Mirabegron and Their Combination on the Development of Doxorubicin-Induced Chronic Cardiotoxicity in a Rat Model.International journal of molecular sciences · 2022Article
- Hepatoprotective Effect of Mitochondria-Targeted Antioxidant Mito-TEMPO against Lipopolysaccharide-Induced Liver Injury in Mouse.Mediators of inflammation · 2022Article
- HSP27 role in cardioprotection by modulating chemotherapeutic doxorubicin-induced cell death.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Matrix Metalloproteinases and Their Role in Mechanisms Underlying Effects of Quercetin on Heart Function in Aged Zucker Diabetic Fatty Rats.International journal of molecular sciences · 2021Article
- Detecting early onset of anthracyclines-induced cardiotoxicity using a novel panel of biomarkers in West-Virginian population with breast cancer.Scientific reports · 2021Article
- Analysis of Models of Doxorubicin-Induced Cardiomyopathy in Rats and Mice. A Modern View From the Perspective of the Pathophysiologist and the Clinician.Frontiers in pharmacology · 2021Review
- Protective Effects of Oroxylin A against Doxorubicin-Induced Cardiotoxicity via the Activation of Sirt1 in Mice.Oxidative medicine and cellular longevity · 2021Article
- The role of Nrf2 and PPARgamma in the improvement of oxidative stress in hypertension and cardiovascular diseases.Physiological research · 2020Review
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo investigate the role of matrix metalloproteinases (MMPs) in the responses of rats to a prolonged doxorubicin (DOX) treatment.
methodsMale Wistar rats were used. DOX was administered by intraperitoneal injections of seven doses (cumulative dose was 15 mg/kg). Control animals were treated with saline. Tissue or plasma samples were collected at four and eight weeks after the application of the last dose. Protein levels were determined by immunoblot assay, and MMP activities were measured by gelatin zymography. Superoxide content was analyzed using a lucigenin chemiluminescence assay and superoxide dismutase (SOD) activities with a SOD assay kit. Qualitative structural alterations of the heart were characterized by transmission electron microscopy.
resultsSystolic blood pressure was higher in DOX-treated rats as compared with the control rats at 8 weeks after treatment. In contrast, there were no differences in the heart rate between the control and DOX-treated rats. DOX treatment caused marked heterogeneous subcellular alterations of cardiomyocytes and structural disorganizations of the cardiac extracellular space. The effects of DOX were linked to a stimulation of plasma MMP-2 and MMP-9 activities that had already increased by 4 weeks after the end of the treatment. In the left ventricle, however, DOX only led to increased MMP-2 activation at 8 weeks after the end of treatment. These changes in tissue MMP-2 were connected with stimulation of Akt kinase activation, inhibition of SOD, an increase in superoxide levels, induction of iNOS protein expression and caspase-3 activation.
conclusionOur results show that MMPs are involved in the chronic cardiotoxicity of DOX in rats. The data also suggest that reactive oxygen species (superoxide), NO production (iNOS) and the Akt kinase pathway can modulate MMP-2 activities in rat hearts influenced by DOX.
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