Korean J Pediatr.  2017 Nov;60(11):365-372. 10.3345/kjp.2017.60.11.365.

Apoptosis and remodeling in adriamycin-induced cardiomyopathy rat model

• Hong YM
• Lee H
• Cho MS
• Kim KC

• KMID: 2396606
• DOI: http://doi.org/10.3345/kjp.2017.60.11.365

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-α, 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.

Keyword

Doxorubicin; Cardiomyopathies; Apoptosis; Ventricular remodeling

MeSH Terms

Animals
Apoptosis*
Ascites
B-Lymphocytes
Blotting, Western
Cardiomyopathies*
Caspase 3
Collagen
Depression
Doxorubicin
Echocardiography
Fibrosis
Free Radicals
Gene Expression
Heart Failure
Heart Ventricles
Humans
Hypertrophy, Left Ventricular
Injections, Intraperitoneal
Interleukin-6
Interleukins
Male
Models, Animal*
Natriuretic Peptide, Brain
Necrosis
Rats*
Rats, Sprague-Dawley
Troponin I
Up-Regulation
Ventricular Remodeling
Caspase 3
Collagen
Doxorubicin
Free Radicals
Interleukin-6
Interleukins
Natriuretic Peptide, Brain
Troponin I