Enalapril in Combination with Benznidazole Reduces Cardiac Inflammation and Creatine Kinases in Mice Chronically Infected with Trypanosoma cruzi

Abstract

Abstract. The protozoan Trypanosoma cruzi triggers an inflammatory process in mammalian

Could angiotensin-modulating drugs be relevant for the treatment of Trypanosoma cruzi infection? A systematic review of preclinical and clinical evidence

“…Most studies indicated that RAS-modulating drugs were effective in reducing parasitaemia (Chumbinho et al ., 2012; Leite et al ., 2017) and mortality (de Paula Costa et al ., 2010; Chumbinho et al ., 2012; Penitente et al ., 2015). Conversely, parasitaemia was unchanged by enalapril (Penitente et al ., 2015), while high doses of captopril (75 mg L −1 ) increased the animals’ mortality with no impact on heart parasitism (Leon et al ., 2003).…”

“…Most studies indicated that RAS-modulating drugs were effective in reducing parasitaemia (Chumbinho et al ., 2012; Leite et al ., 2017) and mortality (de Paula Costa et al ., 2010; Chumbinho et al ., 2012; Penitente et al ., 2015). Conversely, parasitaemia was unchanged by enalapril (Penitente et al ., 2015), while high doses of captopril (75 mg L −1 ) increased the animals’ mortality with no impact on heart parasitism (Leon et al ., 2003). In general, RAS-modulating drugs increased IL-10 plasma levels (Penitente et al ., 2015; Leite et al ., 2017) and reduced TNF- α , IFN- γ , CCL2 circulating levels and myocarditis severity (de Paula Costa et al ., 2010; Penitente et al ., 2015; Leite et al ., 2017).…”

“…There is evidence that molecules of the renin-angiotensin system (RAS), especially angiotensins, are involved in the pathogenesis of Chagas disease (Botoni et al ., 2007; Teixeira et al ., 2011). Considering that molecules such as angiotensin II (Ang II) and angiotensin 1–7 (Ang 1–7) may alter parasitaemia and mortality (Leon et al ., 2003; de Paula Costa et al ., 2010) in T. cruzi -infected mice, chemotherapy based on RAS-modulating drugs such as enalapril, captopril and losartan have been suggested as potentially useful in the treatment of Chagas disease (Botoni et al ., 2013; Penitente et al ., 2015). As the immune response is the main line of defence against T. cruzi , the antiparasitic potential of RAS-modulating drugs appears to be dependent on the effect of RAS molecules on innate and acquired immune cells (de Paula Costa et al ., 2010; Santos et al ., 2010).…”

Influence of environmental enrichment on the behavior and physiology of mice infected by Trypanosoma cruzi

“…These mice were maintained under the same conditions as the other animals (acclimation period: 4 weeks). New animals were required since the peak of parasitemia occurred 27 days after infection; in the original group, this peak occurred before the enrichment treatment, preventing assessment of parasitemia 35 .…”

Doxycycline and Benznidazole Reduce the Profile of Th1, Th2, and Th17 Chemokines and Chemokine Receptors in Cardiac Tissue from ChronicTrypanosoma cruzi-Infected Dogs

“…On the other hand, chronic cardiac inflammation induced by T. cruzi is a harmful and silent event that occurs due to the failure in resolving the acute inflammation and/or due to the persistence of the parasitic stimulus. The involvement and importance of CK and CKR to the generation of the chronic cardiomyopathy induced by T. cruzi were previously highlighted by our group, in humans and in experimental animals (rodent and dog) [ 12 , 14 – 17 ]. Even at this chronic stage, IFN- γ and TNF persist as essential cytokines, maintaining the migration of T cells to consolidate the cardiomyopathy by increasing the expression of CCL5 (RANTES), CCL2 (MCP-1), CXCL10 (IP-10), and CXCL9 (MIG) as well as enhancing intercellular adhesion and vascular cell adhesion molecules [ 7 , 12 ].…”