Short-term therapy with simvastatin reduces inflammatory mediators and heart inflammation during the acute phase of experimental Chagas disease
Trypanosoma cruzi infection induces progressive cardiac inflammation that leads to fibrosis and modifications in the heart architecture and functionality. Statins, such as 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, have been studied due to their pleiotropic roles in modula...
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| Format: | Article |
| Language: | English |
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Fundação Oswaldo Cruz (FIOCRUZ)
2012-06-01
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| Series: | Memorias do Instituto Oswaldo Cruz |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762012000400012&lng=en&tlng=en |
| _version_ | 1797757891042607104 |
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| author | Rafael Rodrigues Silva Deena Shrestha-Bajracharya Camila Megale Almeida-Leite Rômulo Leite Maria Terezinha Bahia Andre Talvani |
| author_facet | Rafael Rodrigues Silva Deena Shrestha-Bajracharya Camila Megale Almeida-Leite Rômulo Leite Maria Terezinha Bahia Andre Talvani |
| author_sort | Rafael Rodrigues Silva |
| collection | DOAJ |
| description | Trypanosoma cruzi infection induces progressive cardiac inflammation that leads to fibrosis and modifications in the heart architecture and functionality. Statins, such as 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, have been studied due to their pleiotropic roles in modulating the inflammatory response. Our goal was to evaluate the effects of simvastatin on the cardiac inflammatory process using a cardiotropic strain of T. cruzi in a murine model of Chagas cardiomyopathy. C57BL/6 mice were infected with 500 trypomastigotes of the Colombian strain of T. cruzi and treated with an oral dose of simvastatin (20 mg/Kg/day) for one month and inflammatory and morphometric parameters were subsequently evaluated in the serum and in the heart, respectively. Simvastatin reduced the total cholesterol and inflammatory mediators (interferon-gamma, tumour necrosis factor-alpha, CCL2 and CCL5) in the serum and in the heart tissue at 30 days post-infection. Additionally, a proportional reduction in heart weight and inflammatory infiltration was observed. Simvastatin also reduced epimastigote proliferation in a dose-dependent manner in vitro and was able to reduce blood trypomastigotes and heart amastigote nests during the acute phase of Chagas disease in vivo. Based on these data, we conclude that simvastatin exerts a modulatory effect on the inflammatory mediators that are elicited by the Colombian strain of T. cruzi and ameliorates the heart damage that is observed in a murine model of Chagas disease. |
| first_indexed | 2024-03-12T18:22:05Z |
| format | Article |
| id | doaj.art-5a975d757771442d80eae9f2fdec4489 |
| institution | Directory Open Access Journal |
| issn | 1678-8060 |
| language | English |
| last_indexed | 2024-03-12T18:22:05Z |
| publishDate | 2012-06-01 |
| publisher | Fundação Oswaldo Cruz (FIOCRUZ) |
| record_format | Article |
| series | Memorias do Instituto Oswaldo Cruz |
| spelling | doaj.art-5a975d757771442d80eae9f2fdec44892023-08-02T08:46:56ZengFundação Oswaldo Cruz (FIOCRUZ)Memorias do Instituto Oswaldo Cruz1678-80602012-06-01107451352110.1590/S0074-02762012000400012S0074-02762012000400012Short-term therapy with simvastatin reduces inflammatory mediators and heart inflammation during the acute phase of experimental Chagas diseaseRafael Rodrigues Silva0Deena Shrestha-Bajracharya1Camila Megale Almeida-Leite2Rômulo Leite3Maria Terezinha Bahia4Andre Talvani5Universidade Federal de Ouro PretoUniversidade Federal de Ouro PretoUniversidade Federal de Ouro PretoUniversidade Federal de Ouro PretoUniversidade Federal de Ouro PretoUniversidade Federal de Ouro PretoTrypanosoma cruzi infection induces progressive cardiac inflammation that leads to fibrosis and modifications in the heart architecture and functionality. Statins, such as 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, have been studied due to their pleiotropic roles in modulating the inflammatory response. Our goal was to evaluate the effects of simvastatin on the cardiac inflammatory process using a cardiotropic strain of T. cruzi in a murine model of Chagas cardiomyopathy. C57BL/6 mice were infected with 500 trypomastigotes of the Colombian strain of T. cruzi and treated with an oral dose of simvastatin (20 mg/Kg/day) for one month and inflammatory and morphometric parameters were subsequently evaluated in the serum and in the heart, respectively. Simvastatin reduced the total cholesterol and inflammatory mediators (interferon-gamma, tumour necrosis factor-alpha, CCL2 and CCL5) in the serum and in the heart tissue at 30 days post-infection. Additionally, a proportional reduction in heart weight and inflammatory infiltration was observed. Simvastatin also reduced epimastigote proliferation in a dose-dependent manner in vitro and was able to reduce blood trypomastigotes and heart amastigote nests during the acute phase of Chagas disease in vivo. Based on these data, we conclude that simvastatin exerts a modulatory effect on the inflammatory mediators that are elicited by the Colombian strain of T. cruzi and ameliorates the heart damage that is observed in a murine model of Chagas disease.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762012000400012&lng=en&tlng=enChagas cardiomyopathyTrypanosoma cruzisimvastatinchemokinesinflammation |
| spellingShingle | Rafael Rodrigues Silva Deena Shrestha-Bajracharya Camila Megale Almeida-Leite Rômulo Leite Maria Terezinha Bahia Andre Talvani Short-term therapy with simvastatin reduces inflammatory mediators and heart inflammation during the acute phase of experimental Chagas disease Memorias do Instituto Oswaldo Cruz Chagas cardiomyopathy Trypanosoma cruzi simvastatin chemokines inflammation |
| title | Short-term therapy with simvastatin reduces inflammatory mediators and heart inflammation during the acute phase of experimental Chagas disease |
| title_full | Short-term therapy with simvastatin reduces inflammatory mediators and heart inflammation during the acute phase of experimental Chagas disease |
| title_fullStr | Short-term therapy with simvastatin reduces inflammatory mediators and heart inflammation during the acute phase of experimental Chagas disease |
| title_full_unstemmed | Short-term therapy with simvastatin reduces inflammatory mediators and heart inflammation during the acute phase of experimental Chagas disease |
| title_short | Short-term therapy with simvastatin reduces inflammatory mediators and heart inflammation during the acute phase of experimental Chagas disease |
| title_sort | short term therapy with simvastatin reduces inflammatory mediators and heart inflammation during the acute phase of experimental chagas disease |
| topic | Chagas cardiomyopathy Trypanosoma cruzi simvastatin chemokines inflammation |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762012000400012&lng=en&tlng=en |
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