Short-term therapy with simvastatin reduces inflammatory mediators and heart inflammation during the acute phase of experimental Chagas disease

Abstract

Trypanosoma cruzi infection induces progressive cardiac inflammation that leads to fibrosis and modifications in the heart architecture and functionality. Statins,

Potential Role of Carvedilol in the Cardiac Immune Response Induced by Experimental Infection with Trypanosoma cruzi

“…In parallel to the search for compounds with antiparasitic activity, our group has been evaluating the potential immunomodulatory effects of drugs managed in clinical routine to chagasic patients. These therapies (simvastatin, enalapril, losartan, and doxycycline) perform primarily cardiovascular application, but in experimental models and in humans, they also work in the inflammatory response induced by T. cruzi [11–13]. Additionally, some of them may also act, directly or indirectly, in the survival of these protozoa [11, 14].…”

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

“…In this context, well-known cardiovascular therapeutic options (e.g., ACE-inhibitors, β-blockers, statins) have gained new interest because of their more recently described modulatory properties over the release of inflammatory cytokines and chemokines, the cellular infiltration, and fibrosis leading to improvements in ventricular cardiac function in experimental and human T. cruzi studies. 8,[10][11][12] Our group previously described, in an experimental model of acute infection by T. cruzi, a relevant role for the enalapril using the Colombian strain of the parasite whose characteristic feature is to cause high systemic and cardiac inflammation in C57BL/6 mice. In this study, the short treatment with 25 mg/kg/day of enalapril was capable to reduce circulating parasites, heart tissue inflammation and plasma IFN-γ, TNF-α, and CCL5/ RANTES, suggesting a protective effect to this ACE inhibitor to the chronic stage of the infection.…”

“…[2][3][4] Since the presence of T. cruzi is the switch for inducing and maintaining the inflammatory process running in the heart tissue, three cardinal therapeutic strategies are proposed: 1) an antiparasitic drug, where benznidazole is considered a standard treatment but still ineffective to those symptomatic individuals in chronic stage of Chagas cardiopathy 5 ; 2) drugs that act direct on the cardiac dysfunction avoiding progressive failure of the organ-for example, diuretics, digitals, β-blockers, and angiotensin-converting enzyme (ACE) inhibitors 6,7 and, more recently, 3) drugs that act in controlling the over-reactivity of the immune system avoiding severe destruction in the heart during chronic stage of the infection-for example, statins and ACE inhibitors. [8][9][10][11][12] ACE inhibitors have been shown to be efficacious not only as therapies against hypertension and protection against left ventricular hypertrophy but also in the regulation of the immune system related to distinct diseases, including the T. cruziinduced pathologies. 9,[13][14][15] Their actions are based on the angiotensin II, a key factor in the renin-angiotensin system that plays an essential role in the regulation of blood pressure, and that also interferes in the cardiac inflammatory activity through the activation of the nuclear factor kappaB (NF-κB) and in the production of inflammatory cytokines and chemokines.…”

The Effects of the Combination of a Refined Carbohydrate Diet and Exposure to Hyperoxia in Mice

“…The salt content of the supernatant was adjusted to be 0.14 M sodium chloride and 0.01 M sodium phosphate at a pH of 7.4 prior to determination of the concentrations of TNF- α , IFN- γ , and IL-10 using commercially available ELISA kits (Bio Source International, Inc., CA, USA) and leptin (PeproTech, London, United Kingdom) according to the manufacturer's guidelines. All samples were measured in duplicate [9, 35]. …”