Losartan Reduces Remodeling and Apoptosis in an Adriamycin-Induced Cardiomyopathy Rat Model
Background: The use of Adriamycin (ADR), also known as doxorubicin, as a chemotherapy agent is limited by its detrimental adverse effects, especially cardiotoxicity. Recent studies have emphasized the crucial role of angiotensin II (Ang-II) in the development of ADR-induced cardiomyopathy. This s...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Korean Society for Thoracic & Cardiovascular Surgery
2023-09-01
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| Series: | Journal of Chest Surgery |
| Subjects: |
| Summary: | Background: The use of Adriamycin (ADR), also known as doxorubicin, as a chemotherapy
agent is limited by its detrimental adverse effects, especially cardiotoxicity. Recent
studies have emphasized the crucial role of angiotensin II (Ang-II) in the development of
ADR-induced cardiomyopathy. This study aimed to explore the potential cardioprotective
effects of losartan in a rat model of ADR-induced cardiomyopathy.
Methods: Male Sprague-Dawley rats were randomly divided into 3 groups: a control
group (group C), an ADR-treated group (ADR 5 mg/kg/wk for 3 weeks via intraperitoneal
injections; group A), and co-treatment of ADR with losartan group (same dose of ADR and
losartan; 10 mg/kg/day per oral for 3 weeks; group L). Western blot analysis was conducted
to demonstrate changes in brain natriuretic peptide, collagen 1, tumor necrosis factor
(TNF)-α, interleukin-6, matrix metalloproteinase (MMP)-2, B-cell leukemia/lymphoma (Bcl)-
2, Bcl-2-associated X (Bax), and caspase-3 protein expression levels in left ventricular (LV)
tissues from each group.
Results: Losartan administration reduced LV hypertrophy, collagen content, and the expression
of pro-inflammatory factors TNF-α and MMP-2 in LV tissue. In addition, losartan
led to a decrease in the expression of the pro-apoptotic proteins Bax and caspase-3 and an
increase in the expression of the anti-apoptotic protein Bcl-2. Moreover, losartan treatment
induced a reduction in the apoptotic area compared to group A.
Conclusion: In an ADR-induced cardiomyopathy rat model, co-administration of ADR
with losartan presented cardioprotective effects by attenuating LV hypertrophy, pro-inflammatory
factors, and apoptosis in LV tissue. |
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| ISSN: | 2765-1606 2765-1614 |