enalapril and benzonidazole

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.

Topics: Animals; Animals, Laboratory; Chagas Disease; Enalapril; Mice; Mice, Inbred C57BL; Nitroimidazoles; Trypanocidal Agents; Trypanosoma cruzi

The protozoan Trypanosoma cruzi triggers an inflammatory process in mammalian heart causing events such as fibrosis, changes in the architecture and functionality in this organ. Enalapril, an angiotensin II-converting enzyme inhibitor, is a drug prescribed to ameliorate this heart dysfunction, and appears to exert a potential role in immune system regulation. Our aim was to evaluate the chronic cardiac inflammatory parameters after therapeutic treatment with enalapril and benznidazole in C57BL/6 mice infected with the VL-10 strain of T. cruzi. After infection, animals were treated with oral doses of enalapril (25 mg/kg), benznidazole (100 mg/kg), or both during 30 days. Morphometric parameters and levels of chemokines (CCL2, CCL5), IL-10, creatine kinases (CKs), and C-reactive protein were evaluated in the heart and serum at the 120th day of infection. Enalapril alone or in combination with benznidazole did not change the number of circulating parasites, but reduced cardiac leukocyte recruitment and total collagen in the cardiac tissue. Interestingly, the combination therapy (enalapril/benznidazole) also reduced the levels of chemokines, CK and CK-MB, and C-reactive proteins in chronic phase. In conclusion, during the chronic experimental T. cruzi infection, the combination therapy using enalapril plus benznidazole potentiated their immunomodulatory effects, resulting in a low production of biomarkers of cardiac lesions.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Chagas Cardiomyopathy; Enalapril; Inflammation; Male; Mice; Mice, Inbred C57BL; Nitroimidazoles; Trypanocidal Agents; Trypanosoma cruzi