Protective Role of Acetylsalicylic Acid in Experimental Trypanosoma cruzi Infection: Evidence of a 15-epi- Lipoxin A4-Mediated EffectReportar como inadecuado




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Resumen

Chagas’ disease, produced by Trypanosoma cruzi, affects more than 8 million people, producing approximately 10,000deaths each year in Latin America. Migration of people from endemic regions to developed countries has expanded the riskof infection, transforming this disease into a globally emerging problem. PGE2 and other eicosanoids contribute to cardiacfunctional deficits after infection with T. cruzi. Thus, the inhibition of host cyclooxygenase COX enzyme emerges as apotential therapeutic target. In vivo studies about the effect of acetylsalicylic acid ASA upon T. cruzi infection arecontroversial, and always report the effect of ASA at a single dose. Therefore, we aimed to analyze the effect of ASA atdifferent doses in an in vivo model of infection and correlate it with the production of arachidonic acid metabolites. ASAdecreased 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 thisobservation was related to the metabolic shift toward the production of 5-lipoxygenase derivatives, and although we didnot observe an increase in LTB4 production in infected RAW cells and mice infected, we did find an increase in 15-epi-LXA4an ASA-triggered lipoxin. We also found high levels of 15-epi-LXA4 in T. cruzi infected mice treated with the low doses ofASA, while the high ASA doses decreased 15-epi-LXA4 levels. Importantly, 15-epi-LXA4 prevented parasitemia, mortality, andcardiac changes in vivo and restored the protective role in the treatment with a high dose of ASA. This is the first reportshowing the production of ASA-triggered lipoxins in T. cruzi infected mice, which demonstrates the role of this lipid as ananti-inflammatory molecule in the acute phase of the disease.Nota general

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Autor: Molina Berríos, Alfredo; - Campos Estrada, Carolina; - Henriquez, Natalia; - López Muñoz, Rodrigo; - Faúndez, Mario; - Torres

Fuente: http://repositorio.uchile.cl/



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