Effects of Erythropoietin on Acute and Chronic Phases of Experimental Chagas Disease on Mice

Abstract

Chagas disease, caused by the protozoan Trypanosoma cruzi, affects about seven million people worldwide, mostly in Latin America. However, this disease has become cosmopolitan due to migration of people infected by the protozoan. The most important clinical manifestation of the disease is cardiomyopathy, which develops in approximately 30% of individuals with chronic infection. Despite reducing parasite load, trypanocidal drugs have no efficacy on the progression of lesions, doing little to decrease morbidity. Erythropoietin (Epo), a key‐regulator of erythropoiesis, also has a cardioprotective effect by reducing the processes of apoptosis, inflammation and myocardial ischemia through the formation of new blood vessels. However, it is unknown whether this protein can be effectively used in treatment of Chagas cardiomyopathy. Thereby, this study aims to investigate the possible cardioprotective effect of Epo on experimental Chagas disease. C57BL/6 mice were divided into five groups (n = 8 in each): not infected and not treated (NINT); infected with T. cruzi, not treated (INT); treated with Epo before infection (EpoI); infected and treated with Epo in the acute phase of the disease (IEpoA) and infected and treated with Epo in the chronic phase (IEpoC). Mice were infected by intraperitoneal route (i.p.) with 105 trypomastigotes of the Colombiana strain of T. cruzi. Mice received 2000 U/kg of Epo i.p. on alternate days as follow: during 30 days before the infection for the group EpoI (protective effect of Epo); from 1st to 30th days postinfection (dpi) for the group IEpoA and from 120th to 150th dpi for the group IEpoC (therapeutic effect of Epo). The animals were euthanized at 180 dpi. Histopathological analysis of heart, spleen and large intestine were performed. The parasite load in blood, heart, spleen and large intestine was determined by qPCR. Histopathological analysis demonstrated necrosis of cardiomyocytes (NC), multifocal inflammatory infiltrates (MII) in the perivascular and interstitial regions in heart of mice and damage in spleen tissue of INT (p<0.006). Administration of Epo reduced both NC and MII in the perivascular region in heart with less effect for the IEpoA (p<0.006). No cardiac fibrosis was observed in any group, neither lesions in large intestine. Similar profiles of blood parasitaemia were observed in groups who received Epo, with a higher number of parasites in EpoI and IEpoC groups. The latter presented parasitic load significantly higher than INT. In cardiac tissue, qPCR detected T. cruzi DNA in all infected mice without significant difference between groups. In spleen tissue the parasite load was extremely low with no significant difference between groups. For the large intestine, the number of parasite was similar for all infected group in spite of treatment with Epo. Our results show that Epo has no trypanocidal effect but may have allowed the presence of a greater number of parasites in the blood. However, histopathological analysis from heart suggests a cardioprotective effect of Epo on Chagas disease.Support or Funding InformationThis work was funded by FAPDFThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.