The immunomodulatory effects of the Enalapril in combination with Benznidazole during acute and chronic phases of the experimental infection with Trypanosoma cruzi

Abstract

Trypanosoma cruzi infection triggers a chronic inflammatory process responsible for the alterations in the extracellular matrix and functionality of the heart. The angiotensin converting enzyme (ACE) inhibitors affects T. cruzi in vitro surveillance and modulates in vivo some inflammatory mediators. In this study, we investigated the treatment with an ACE inhibitor (Enalapril) and the Benznidazole (Bz) in a single and combination therapies (CT) in C57BL/6 mice infected with VL-10 strain of the T. cruzi. Animals were treated during 20days with different doses of Bz (100, 80, 60mg/kg), Enalapril (25, 20, 15mg/kg) and their CT (100+25; 80+20; 60+15mg/kg) and euthanized at 30° (acute) and at 120° (chronic) days post infection. The plasma and heart were processed for immunopathological investigations. Our data shown that Bz and Enalapril controlled, in part, the parasite replication and reduced plasma levels of TNF, CCL2 and CCL5 in the acute and in chronic phase of infection. However, the CT doses reduced in around 20% the inflammatory parameters obtained with the Bz therapy. The CT doses of 100+25 and 80+20mg/kg increased the IL-10 levels and reduced the cardiac inflammation while Bz inhibited the collagen neogenesis in the infection. In conclusion, we assume that the CT administrated in the initial stage of infection, presents a minor immunomodulatory effect when the VL-10 strain of T. cruzi is used. In contrast, Bz and Enalapril in monotherapies persist suggesting a potential protection against cardiac damages during experimental T. cruzi infection.

Keywords: Benznidazole; Chemokines; Enalapril; Heart inflammation; Trypanosoma cruzi.