Ghrelin: potencial cardioprotective and immunonodulatory effects in acute and chronic phase of Chagas Disease

Abstract

Chagas disease treatment remains partially ineffective, involving specific therapies directed to the parasite as well as adjuvant therapies for the clinical manifestations. In Brazil, benznidazole (N-benzyl-2-nitroimidazole-acetamide) is the only drug available for the aetiological treatment but can cause side effects to the patients. Studies show that Ghrelin has an important cardioprotective, anti-apoptotic, anti-oxidative and anti-inflammatory functions. However, little is known about the immunomodulatory action of Ghrelin in Chagas disease. The search for new alternative therapies for the control of Chagas' disease has been the main goal of our research group. In this study we will evaluate the cardioprotective and immunomodulatory effects of the Ghrelin, associated or not to benznidazole, in acute and chronic phase of experimental Chagas disease. Wistar rats infected with the Y strain of T. cruzi will be used as experimental model. Evaluation will be conducted through different immunological parameters such as dosages of pro and anti inflammatory cytokines (IL-1, IL-6, IL-10, IL-12, TNF-alfa, TGF-beta and IFN-gama), cardiac biomarkers (Troponin I, T and NT-ProBNP), quantification of nitric oxide (NO), apoptosis, splenocytes lymphoproliferation (CFSE) and phenotyping of lymphocytes populations (TCD3+, TCD4+, TCD8+ and NK cells) by flow cytometry. Quantification of blood parasitism and heart histological analysis of infected and treated animals will be performed. Electrocardiographic parameters and doppler echocardiography will be evaluated in rats treated with ghrelin in acute and chronic phase of the Chagas disease. (AU)