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: |
| _version_ | 1797692728569495552 |
|---|---|
| author | Hyeon A Kim Kwan Chang Kim Hyeryon Lee Young Mi Hong |
| author_facet | Hyeon A Kim Kwan Chang Kim Hyeryon Lee Young Mi Hong |
| author_sort | Hyeon A Kim |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T02:32:49Z |
| format | Article |
| id | doaj.art-63ca1461a75546c194ec90c5ca34f8b0 |
| institution | Directory Open Access Journal |
| issn | 2765-1606 2765-1614 |
| language | English |
| last_indexed | 2024-03-12T02:32:49Z |
| publishDate | 2023-09-01 |
| publisher | Korean Society for Thoracic & Cardiovascular Surgery |
| record_format | Article |
| series | Journal of Chest Surgery |
| spelling | doaj.art-63ca1461a75546c194ec90c5ca34f8b02023-09-05T06:51:38ZengKorean Society for Thoracic & Cardiovascular SurgeryJournal of Chest Surgery2765-16062765-16142023-09-0156529530310.5090/jcs.23.044Losartan Reduces Remodeling and Apoptosis in an Adriamycin-Induced Cardiomyopathy Rat ModelHyeon A Kim0https://orcid.org/0000-0002-0648-948XKwan Chang Kim1https://orcid.org/0000-0001-8297-5415Hyeryon Lee2https://orcid.org/0000-0002-8566-7503Young Mi Hong3https://orcid.org/0000-0002-6600-7876Asan Medical CenterEwha Womans University School of MedicineEwha Womans University School of MedicineEwha Womans University School of MedicineBackground: 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.doxorubicincardiomyopathiesapoptosisventricular remodelinglosartan |
| spellingShingle | Hyeon A Kim Kwan Chang Kim Hyeryon Lee Young Mi Hong Losartan Reduces Remodeling and Apoptosis in an Adriamycin-Induced Cardiomyopathy Rat Model Journal of Chest Surgery doxorubicin cardiomyopathies apoptosis ventricular remodeling losartan |
| title | Losartan Reduces Remodeling and Apoptosis in an Adriamycin-Induced Cardiomyopathy Rat Model |
| title_full | Losartan Reduces Remodeling and Apoptosis in an Adriamycin-Induced Cardiomyopathy Rat Model |
| title_fullStr | Losartan Reduces Remodeling and Apoptosis in an Adriamycin-Induced Cardiomyopathy Rat Model |
| title_full_unstemmed | Losartan Reduces Remodeling and Apoptosis in an Adriamycin-Induced Cardiomyopathy Rat Model |
| title_short | Losartan Reduces Remodeling and Apoptosis in an Adriamycin-Induced Cardiomyopathy Rat Model |
| title_sort | losartan reduces remodeling and apoptosis in an adriamycin induced cardiomyopathy rat model |
| topic | doxorubicin cardiomyopathies apoptosis ventricular remodeling losartan |
| work_keys_str_mv | AT hyeonakim losartanreducesremodelingandapoptosisinanadriamycininducedcardiomyopathyratmodel AT kwanchangkim losartanreducesremodelingandapoptosisinanadriamycininducedcardiomyopathyratmodel AT hyeryonlee losartanreducesremodelingandapoptosisinanadriamycininducedcardiomyopathyratmodel AT youngmihong losartanreducesremodelingandapoptosisinanadriamycininducedcardiomyopathyratmodel |