Doxycycline Attenuates Doxorubicin-Induced Cardiotoxicity by Improving Myocardial Energy Metabolism in Rats
Aim: Evaluate the influence of doxycycline, an anti-inflammatory and matrix metalloproteinase (MMP) inhibitor, on the attenuation of chronic doxorubicin-induced cardiotoxicity in rats. Methods: We allocated male Wistar rats into four groups: control (C), doxorubicin (D), doxycycline (inhibitor of MM...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | Journal of Cardiovascular Development and Disease |
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| Online Access: | https://www.mdpi.com/2308-3425/9/8/254 |
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| author | Danielle Dantas Amanda Gomes Pereira Anderson Seiji Soares Fujimori Ana Paula Dantas Ribeiro Carol Cristina Vágula de Almeida Silva Marina Gaiato Monte Camila Renata Corrêa Ana Angélica Fernandes Silmeia Garcia Zanati Bazan Paula Schmidt Azevedo Marcos Ferreira Minicucci Sergio Alberto Rupp de Paiva Leonardo Antônio Mamede Zornoff Bertha Furlan Polegato |
| author_facet | Danielle Dantas Amanda Gomes Pereira Anderson Seiji Soares Fujimori Ana Paula Dantas Ribeiro Carol Cristina Vágula de Almeida Silva Marina Gaiato Monte Camila Renata Corrêa Ana Angélica Fernandes Silmeia Garcia Zanati Bazan Paula Schmidt Azevedo Marcos Ferreira Minicucci Sergio Alberto Rupp de Paiva Leonardo Antônio Mamede Zornoff Bertha Furlan Polegato |
| author_sort | Danielle Dantas |
| collection | DOAJ |
| description | Aim: Evaluate the influence of doxycycline, an anti-inflammatory and matrix metalloproteinase (MMP) inhibitor, on the attenuation of chronic doxorubicin-induced cardiotoxicity in rats. Methods: We allocated male Wistar rats into four groups: control (C), doxorubicin (D), doxycycline (inhibitor of MMP, IM), and Dox + doxycycline (DIM). Groups IM and DIM received doxycycline (5 mg/kg, IP) once a week for 4 weeks. In addition, 48 h after every doxycycline injection, groups D and DIM received Dox (5 mg/kg, IP). We performed echocardiogram and evaluated TIMP-4 and collagen I protein expression, MMP-2 activity, and oxidative stress and myocardial metabolism. Results: Doxorubicin promotes left atrium (LA) and left ventricle (LV) dilatation and decreases in LV fractional shortening, which was improved by doxycycline. Moreover, doxycycline attenuated the LV cardiomyocyte hypertrophy and collagen type I expression. Doxorubicin increased phosphofructokinase and decreased beta-hydroxyacyl Co-A dehydrogenase, pyruvate dehydrogenase, citrate synthase, and ATP synthase activity, which was partially attenuated by doxycycline. Lastly, doxycycline improved antioxidant enzyme activity in the DIM group. Conclusion: Doxorubicin increases oxidative stress and promotes changes in myocardial energy metabolism, accompanied by structural and functional changes. Doxycycline attenuated the doxorubicin-induced cardiotoxicity, at least in part, through changes in myocardial energy metabolism. |
| first_indexed | 2024-03-09T09:55:46Z |
| format | Article |
| id | doaj.art-da1fd59e3b6c4078af734b2fb880d18f |
| institution | Directory Open Access Journal |
| issn | 2308-3425 |
| language | English |
| last_indexed | 2024-03-09T09:55:46Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Cardiovascular Development and Disease |
| spelling | doaj.art-da1fd59e3b6c4078af734b2fb880d18f2023-12-01T23:49:39ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252022-08-019825410.3390/jcdd9080254Doxycycline Attenuates Doxorubicin-Induced Cardiotoxicity by Improving Myocardial Energy Metabolism in RatsDanielle Dantas0Amanda Gomes Pereira1Anderson Seiji Soares Fujimori2Ana Paula Dantas Ribeiro3Carol Cristina Vágula de Almeida Silva4Marina Gaiato Monte5Camila Renata Corrêa6Ana Angélica Fernandes7Silmeia Garcia Zanati Bazan8Paula Schmidt Azevedo9Marcos Ferreira Minicucci10Sergio Alberto Rupp de Paiva11Leonardo Antônio Mamede Zornoff12Bertha Furlan Polegato13Department of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618687, BrazilDepartment of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618687, BrazilDepartment of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618687, BrazilDepartment of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618687, BrazilDepartment of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618687, BrazilDepartment of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618687, BrazilDepartment of Pathology, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618687, BrazilDepartment of Chemistry and Biochemistry, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618687, BrazilDepartment of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618687, BrazilDepartment of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618687, BrazilDepartment of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618687, BrazilDepartment of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618687, BrazilDepartment of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618687, BrazilDepartment of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618687, BrazilAim: Evaluate the influence of doxycycline, an anti-inflammatory and matrix metalloproteinase (MMP) inhibitor, on the attenuation of chronic doxorubicin-induced cardiotoxicity in rats. Methods: We allocated male Wistar rats into four groups: control (C), doxorubicin (D), doxycycline (inhibitor of MMP, IM), and Dox + doxycycline (DIM). Groups IM and DIM received doxycycline (5 mg/kg, IP) once a week for 4 weeks. In addition, 48 h after every doxycycline injection, groups D and DIM received Dox (5 mg/kg, IP). We performed echocardiogram and evaluated TIMP-4 and collagen I protein expression, MMP-2 activity, and oxidative stress and myocardial metabolism. Results: Doxorubicin promotes left atrium (LA) and left ventricle (LV) dilatation and decreases in LV fractional shortening, which was improved by doxycycline. Moreover, doxycycline attenuated the LV cardiomyocyte hypertrophy and collagen type I expression. Doxorubicin increased phosphofructokinase and decreased beta-hydroxyacyl Co-A dehydrogenase, pyruvate dehydrogenase, citrate synthase, and ATP synthase activity, which was partially attenuated by doxycycline. Lastly, doxycycline improved antioxidant enzyme activity in the DIM group. Conclusion: Doxorubicin increases oxidative stress and promotes changes in myocardial energy metabolism, accompanied by structural and functional changes. Doxycycline attenuated the doxorubicin-induced cardiotoxicity, at least in part, through changes in myocardial energy metabolism.https://www.mdpi.com/2308-3425/9/8/254doxycyclinemyocardial energy metabolismoxidative stressMMP-2collagen ITIMP-4 |
| spellingShingle | Danielle Dantas Amanda Gomes Pereira Anderson Seiji Soares Fujimori Ana Paula Dantas Ribeiro Carol Cristina Vágula de Almeida Silva Marina Gaiato Monte Camila Renata Corrêa Ana Angélica Fernandes Silmeia Garcia Zanati Bazan Paula Schmidt Azevedo Marcos Ferreira Minicucci Sergio Alberto Rupp de Paiva Leonardo Antônio Mamede Zornoff Bertha Furlan Polegato Doxycycline Attenuates Doxorubicin-Induced Cardiotoxicity by Improving Myocardial Energy Metabolism in Rats Journal of Cardiovascular Development and Disease doxycycline myocardial energy metabolism oxidative stress MMP-2 collagen I TIMP-4 |
| title | Doxycycline Attenuates Doxorubicin-Induced Cardiotoxicity by Improving Myocardial Energy Metabolism in Rats |
| title_full | Doxycycline Attenuates Doxorubicin-Induced Cardiotoxicity by Improving Myocardial Energy Metabolism in Rats |
| title_fullStr | Doxycycline Attenuates Doxorubicin-Induced Cardiotoxicity by Improving Myocardial Energy Metabolism in Rats |
| title_full_unstemmed | Doxycycline Attenuates Doxorubicin-Induced Cardiotoxicity by Improving Myocardial Energy Metabolism in Rats |
| title_short | Doxycycline Attenuates Doxorubicin-Induced Cardiotoxicity by Improving Myocardial Energy Metabolism in Rats |
| title_sort | doxycycline attenuates doxorubicin induced cardiotoxicity by improving myocardial energy metabolism in rats |
| topic | doxycycline myocardial energy metabolism oxidative stress MMP-2 collagen I TIMP-4 |
| url | https://www.mdpi.com/2308-3425/9/8/254 |
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