Insights from the use of erythropoietin in experimental Chagas disease. (August 2022)

• Record Type: Journal Article
• Authors: de Castro Nobre, Ana Carolina; Pimentel, Carlos Fernando; do Rêgo, George Magno Sousa; Paludo, Giane Regina; Pereira Neto, Glaucia Bueno; de Castro, Márcio Botelho; Nitz, Nadjar; Hecht, Mariana; Dallago, Bruno; Hagström, Luciana
• Is Part Of: International journal for parasitology. Volume 19(2022)
• Page Start: 65
• Page End: 80
• Publication Date: 2022-08
• Subjects: Trypanosoma cruzi -- Therapeutic drug -- Erythropoietin -- Cardioprotection -- Mice; Parasitic diseases -- Chemotherapy -- Periodicals; Drug resistance -- Periodicals; 616.96061
• DOI: 10.1016/j.ijpddr.2022.05.005
• Languages: English
• ISSNs: 2211-3207

Abstract

Abstract: In addition to the long-established role in erythropoiesis, erythropoietin (Epo) has protective functions in a variety of tissues, including the heart. This is the most affected organ in chronic Chagas disease, caused by the protozoan Trypanosoma cruzi . Despite seven million people being infected with T. cruzi worldwide, there is no effective treatment preventing the disease progression to the chronic phase when the pathological involvement of the heart is often observed. Chronic chagasic cardiomyopathy has a wide variety of manifestations, like left ventricular systolic dysfunction, dilated cardiomyopathy, and heart failure. Since Epo may help maintain cardiac function by reducing myocardial necrosis, inflammation, and fibrosis, this study aimed to evaluate whether the Epo has positive effects on experimental Chagas disease. For that, we assessed the earlier (acute phase) and also the later (chronic phase) use of Epo in infected C57BL/6 mice. Blood cell count, biochemical parameters, parasitic load, and echocardiography data were evaluated. In addition, histopathological analysis was carried out. Our data showed that Epo had no trypanocide effect nor did it modify the production of anti- T. cruzi antibodies. Epo-treated groups exhibited parasitic burden much lower in the heart compared to blood. No pattern of hematological changes was observed combining infection with treatment with Epo. Chronic Epo administration reduced CK-MB serum activity from d0 to d180, irrespectively of T. cruzi infection. Likewise, echocardiography and histological results indicate that Epo treatment is more effective in the chronic phase of experimental Chagas disease. Since treatment is one of the greatest challenges of Chagas disease, alternative therapies should be investigated, including Epo combined with benznidazole. Graphical abstract: Image 1 Highlights: Mice treated with erythropoietin had lower levels of CK-MB regardless of T. cruzi infection. Neither heart fibrosis nor necrosis was seen with erythropoietin in the chronic phase of infection. Heart perivascular inflammation was less frequent with erythropoietin in the chronic phase. The ejection fraction was normal with erythropoietin in the chronic phase of infection. Treatment with erythropoietin in the chronic phase appears to have better results.