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ORIGINAL ARTICLE
Korean J Pediatr 2017 November;60(11) :365-372.
Published online 2017 November 15.       
Apoptosis and remodeling in adriamycin-induced cardiomyopathy rat model
Young Mi Hong1, Hyeryon Lee1, Min-Sun Cho2, Kwan Chang Kim3
1Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea
2Department of Pathology, Ewha Womans University School of Medicine, Seoul, Korea
3Department of Thoracic and Cardiovascular Surgery, Ewha Womans University School of Medicine, Seoul, Korea
Corresponding Author: Kwan Chang Kim ,Tel: +82-2-2650-5151, Fax: +82-2-2650-5152, Email: mdkkchang@ewha.ac.kr
Copyright © 2017 by The Korean Pediatric Society
ABSTRACT
Purpose: The mechanism for the pathogenesis of adriamycin (ADR)-induced cardiomyopathy is not yet known. Different hypotheses include the production of free radicals, an interaction between ADR and nuclear components, and a disruption in cardiac-specific gene expression. Apoptosis has also been proposed as being involved in cardiac dysfunction. The purpose of this study was to determine if apoptosis might play a role in ADR-induced cardiomyopathy.
Methods: Male Sprague-Dawley rats were separated into 2 groups: the control group (C group) and the experimental group (ADR 5 mg/wk for 3 weeks through intraperitoneal injections; A group). Echocardiographic images were obtained at week 3. Changes in caspase-3, B-cell leukemia/lymphoma (Bcl)-2, Bcl-2-associated X (Bax), interleukin (IL)-6, tumor necrosis factor-, brain natriuretic peptide (BNP), troponin I, collagen 1, and collagen 3 protein expression from the left ventricle tissues of C and A group rats were determined by Western blot.
Results: Ascites and heart failure as well as left ventricular hypertrophy were noted in the A group. Ejection fraction and shortening fraction were significantly lower in the A group by echocardiography. The expression of caspase-3, Bax, IL-6, BNP, collagen 1, and collagen 3 were significantly higher in the A group as compared with the C group. Protein expression of Bcl-2 decreased significantly in the A group compared with the C group.
Conclusion: ADR induced an upregulation of caspase-3, Bax, IL-6, and collagen, as well as a depression in Bcl-2. Thus, apoptosis and fibrosis may play an important role in ADR-induced cardiomyopathy.
Keywords: Doxorubicin | Cardiomyopathies | Apoptosis | Ventricular remodeling
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METRICS
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The Preventive Effect of Dexrazoxane and Pentoxifylline on Adriamycin Induced Cardiomyopathy  2005 December;48(12)
Gene Expression of Metalloproteinases, Tissue Inhibitors of Metalloproteinases and Cytokines in Adriamycin-induced Cardiomyopathy  2005 February;48(2)
Serum Lipid Levels and Fatty Acid Metabolism in the Rat with Adriamycin Induced Cardiomyopathy  2000 November;43(11)
Two Cases of Doxorubicin-induced Dilated Cardiomyopathy  1992 June;35(6)
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