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Protective Role of Acetylsalicylic Acid in Experimental Trypanosoma cruzi Infection: Evidence of a 15-epi-Lipoxin A(4)-Mediated Effect

Chagas' disease, produced by Trypanosoma cruzi, affects more than 8 million people, producing approximately 10,000 deaths each year in Latin America. Migration of people from endemic regions to developed countries has expanded the risk of infection, transforming this disease into a globally eme...

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Autores principales: Molina-Berríos, Alfredo, Campos-Estrada, Carolina, Henriquez, Natalia, Faúndez, Mario, Torres, Gloria, Castillo, Christian, Escanilla, Sebastián, Kemmerling, Ulrike, Morello, Antonio, López-Muñoz, Rodrigo A., Maya, Juan D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3630130/
https://www.ncbi.nlm.nih.gov/pubmed/23638194
http://dx.doi.org/10.1371/journal.pntd.0002173
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author Molina-Berríos, Alfredo
Campos-Estrada, Carolina
Henriquez, Natalia
Faúndez, Mario
Torres, Gloria
Castillo, Christian
Escanilla, Sebastián
Kemmerling, Ulrike
Morello, Antonio
López-Muñoz, Rodrigo A.
Maya, Juan D.
author_facet Molina-Berríos, Alfredo
Campos-Estrada, Carolina
Henriquez, Natalia
Faúndez, Mario
Torres, Gloria
Castillo, Christian
Escanilla, Sebastián
Kemmerling, Ulrike
Morello, Antonio
López-Muñoz, Rodrigo A.
Maya, Juan D.
author_sort Molina-Berríos, Alfredo
collection PubMed
description Chagas' disease, produced by Trypanosoma cruzi, affects more than 8 million people, producing approximately 10,000 deaths each year in Latin America. Migration of people from endemic regions to developed countries has expanded the risk of infection, transforming this disease into a globally emerging problem. PGE(2) and other eicosanoids contribute to cardiac functional deficits after infection with T. cruzi. Thus, the inhibition of host cyclooxygenase (COX) enzyme emerges as a potential therapeutic target. In vivo studies about the effect of acetylsalicylic acid (ASA) upon T. cruzi infection are controversial, and always report the effect of ASA at a single dose. Therefore, we aimed to analyze the effect of ASA at different doses in an in vivo model of infection and correlate it with the production of arachidonic acid metabolites. ASA decreased mortality, parasitemia, and heart damage in T. cruzi (Dm28c) infected mice, at the low doses of 25 and 50 mg/Kg. However, this effect disappeared when the high ASA doses of 75 and 100 mg/Kg were used. We explored whether this observation was related to the metabolic shift toward the production of 5-lipoxygenase derivatives, and although we did not observe an increase in LTB(4) production in infected RAW cells and mice infected, we did find an increase in 15-epi-LXA(4) (an ASA-triggered lipoxin). We also found high levels of 15-epi-LXA(4) in T. cruzi infected mice treated with the low doses of ASA, while the high ASA doses decreased 15-epi-LXA(4) levels. Importantly, 15-epi-LXA(4) prevented parasitemia, mortality, and cardiac changes in vivo and restored the protective role in the treatment with a high dose of ASA. This is the first report showing the production of ASA-triggered lipoxins in T. cruzi infected mice, which demonstrates the role of this lipid as an anti-inflammatory molecule in the acute phase of the disease.
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spelling pubmed-36301302013-05-01 Protective Role of Acetylsalicylic Acid in Experimental Trypanosoma cruzi Infection: Evidence of a 15-epi-Lipoxin A(4)-Mediated Effect Molina-Berríos, Alfredo Campos-Estrada, Carolina Henriquez, Natalia Faúndez, Mario Torres, Gloria Castillo, Christian Escanilla, Sebastián Kemmerling, Ulrike Morello, Antonio López-Muñoz, Rodrigo A. Maya, Juan D. PLoS Negl Trop Dis Research Article Chagas' disease, produced by Trypanosoma cruzi, affects more than 8 million people, producing approximately 10,000 deaths each year in Latin America. Migration of people from endemic regions to developed countries has expanded the risk of infection, transforming this disease into a globally emerging problem. PGE(2) and other eicosanoids contribute to cardiac functional deficits after infection with T. cruzi. Thus, the inhibition of host cyclooxygenase (COX) enzyme emerges as a potential therapeutic target. In vivo studies about the effect of acetylsalicylic acid (ASA) upon T. cruzi infection are controversial, and always report the effect of ASA at a single dose. Therefore, we aimed to analyze the effect of ASA at different doses in an in vivo model of infection and correlate it with the production of arachidonic acid metabolites. ASA decreased mortality, parasitemia, and heart damage in T. cruzi (Dm28c) infected mice, at the low doses of 25 and 50 mg/Kg. However, this effect disappeared when the high ASA doses of 75 and 100 mg/Kg were used. We explored whether this observation was related to the metabolic shift toward the production of 5-lipoxygenase derivatives, and although we did not observe an increase in LTB(4) production in infected RAW cells and mice infected, we did find an increase in 15-epi-LXA(4) (an ASA-triggered lipoxin). We also found high levels of 15-epi-LXA(4) in T. cruzi infected mice treated with the low doses of ASA, while the high ASA doses decreased 15-epi-LXA(4) levels. Importantly, 15-epi-LXA(4) prevented parasitemia, mortality, and cardiac changes in vivo and restored the protective role in the treatment with a high dose of ASA. This is the first report showing the production of ASA-triggered lipoxins in T. cruzi infected mice, which demonstrates the role of this lipid as an anti-inflammatory molecule in the acute phase of the disease. Public Library of Science 2013-04-18 /pmc/articles/PMC3630130/ /pubmed/23638194 http://dx.doi.org/10.1371/journal.pntd.0002173 Text en © 2013 Molina-Berríos et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Molina-Berríos, Alfredo
Campos-Estrada, Carolina
Henriquez, Natalia
Faúndez, Mario
Torres, Gloria
Castillo, Christian
Escanilla, Sebastián
Kemmerling, Ulrike
Morello, Antonio
López-Muñoz, Rodrigo A.
Maya, Juan D.
Protective Role of Acetylsalicylic Acid in Experimental Trypanosoma cruzi Infection: Evidence of a 15-epi-Lipoxin A(4)-Mediated Effect
title Protective Role of Acetylsalicylic Acid in Experimental Trypanosoma cruzi Infection: Evidence of a 15-epi-Lipoxin A(4)-Mediated Effect
title_full Protective Role of Acetylsalicylic Acid in Experimental Trypanosoma cruzi Infection: Evidence of a 15-epi-Lipoxin A(4)-Mediated Effect
title_fullStr Protective Role of Acetylsalicylic Acid in Experimental Trypanosoma cruzi Infection: Evidence of a 15-epi-Lipoxin A(4)-Mediated Effect
title_full_unstemmed Protective Role of Acetylsalicylic Acid in Experimental Trypanosoma cruzi Infection: Evidence of a 15-epi-Lipoxin A(4)-Mediated Effect
title_short Protective Role of Acetylsalicylic Acid in Experimental Trypanosoma cruzi Infection: Evidence of a 15-epi-Lipoxin A(4)-Mediated Effect
title_sort protective role of acetylsalicylic acid in experimental trypanosoma cruzi infection: evidence of a 15-epi-lipoxin a(4)-mediated effect
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3630130/
https://www.ncbi.nlm.nih.gov/pubmed/23638194
http://dx.doi.org/10.1371/journal.pntd.0002173
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