Enfermedades de chagas crónica: estrés oxidativo y miocarditis chagásica asociada a la persistencia parasitaria

Chagas disease is a neglected chronic illness with a high social impact that currently affects 8 million people in endemic countries of Latin American. This lifelong infection, also known as American trypanosomiasis, is caused by the protozoan parasite Trypanosoma cruzi. The transmission of the disease is produced by an infected triatomine insect that upon feeding on mammalian blood, deposits feces with infective non-replicative trypomastigote parasite forms which enter the mammalian body mainly through the skin wound produced by the insect. Upon entering the body, the trypomastigotes invade macrophages taking an intracellular replicative form, the amastigote. After replication, the amastigotes transform back to trypomastigotes that invade heart, ganglia and other tissues. Blood trypomastigotes ingested by the same or another triatomine insect transform into replicative, non-infective epimastigotes parasite form in the vector's midgut. These parasites multiply actively; afterwards, the epimastigotes move to the hindgut where they differentiate into infective metacyclic trypomastigotes. Chagas disease mortality and morbidity are mainly due to chronic processes that lead to dysfunction of the cardiac and digestive systems. Considering that approximately one-third of T. cruzi infected humans develop severe chronic disease with irreversible damage to the heart (that ultimately lead to heart failure and the patient's death) it is crucial to understand the mechanisms leading to this pathology. Numerous contributing mechanisms have been suggested to explain the pathogenesis of Chagas heart disease. A consensus is now emerging that parasite persistence is the main factor for the development of the chronic phase of this disease. The host response to T. cruzi persistence infection involves sustained ROS/RNS generation by inflammatory cells and by cardiac mitochondria dysfunction in the heart that leads to longterm oxidative stress of both the cardiac tissue and the parasites inside cardiac cells. ROS/RNS are extremely reactive and generate various lesions in DNA such as base modifications, and chain breaks, among others. If this DNA damage is not repaired, cells trigger the apoptosis process. Thus, to establish parasite persistence in the heart and other host tissues, T. cruzi should repair its own damaged DNA activating DNA repair molecules to insure parasite survival in the host leading to the establishment of the chronic phase of Chagas disease.    

Bibliographic Details

Main Authors:	Valenzuela, L., Barría, C., Sepúlveda, S., Galanti, N., Cabrera, G.
Format:	Digital revista
Language:	spa
Published:	Universidad de Chile. Facultad de Ciencias Veterinarias y Pecuarias 2010
Online Access:	https://avancesveterinaria.uchile.cl/index.php/ACV/article/view/18288
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