A High‐Fat Diet Exacerbates the Course of Experimental Trypanosoma cruzi Infection That Can Be Mitigated by Treatment with Simvastatin

Abstract

The protozoan Trypanosoma cruzi is responsible for triggering a damage immune response in the host cardiovascular system. This parasite has a high affinity for host lipoproteins and uses the low-density lipoprotein (LDL) receptor for its invasion. Assuming that the presence of LDL cholesterol in tissues could facilitate T. cruzi proliferation, dietary composition may affect the parasite-host relationship. Therefore, the aim of this study was to evaluate myocarditis in T. cruzi-infected C57BL/6 mice—acute phase—fed a high-fat diet and treated with simvastatin, a lipid-lowering medication. Animals (n=10) were infected with 5×103 cells of the VL-10 strain of T. cruzi and treated or untreated daily with 20 mg/kg simvastatin, starting 24 h after infection and fed with a normolipidic or high-fat diet. Also, uninfected mice, treated or not with simvastatin and fed with normolipidic or high-fat diet, were evaluated as control groups. Analyses to measure the production of chemokine (C-C motif) ligand 2 (CCL2), interferon- (IFN-) γ, interleukin- (IL-) 10, and tumor necrosis factor (TNF); total hepatic lipid dosage; cholesterol; and fractions, as well as histopathological analysis, were performed on day 30 using cardiac and fat tissues. Our results showed that the high-fat diet increased (i) parasite replication, (ii) fat accumulation in the liver, (iii) total cholesterol and LDL levels, and (iv) the host inflammatory state through the production of the cytokine TNF. However, simvastatin only reduced the production of CCL2 but not that of other inflammatory mediators or biochemical parameters. Together, our data suggest that the high-fat diet may have worsened the biochemical parameters of the uninfected and T. cruzi-infected animals, as well as favored the survival of circulating parasites.

Small molecule mediators of host-T. cruzi-environment interactions in Chagas disease

“…This contrasts with findings in the context of malaria infection, where a high-fat diet impaired Plasmodium liver infection [140]. One caveat with these studies is that many of the high-fat diets are also higher caloric (for instance, [131,136]); thus, the observed effects may reflect caloric differences rather than purely fat-driven effects.…”

“…Several studies analyzed the impact of shifting lipid homeostasis through a high fat diet (Table 1). In the acute stage, worse parasitemia was observed in mice fed a high-fat diet [131][132][133][134], in association with higher cardiac inflammation [131,133], though this contrasts with [135,136]. The functional impact during chronic infection was variable depending on the ventricle [137].…”

Theracurmin Modulates Cardiac Inflammation in Experimental Model of Trypanosoma cruzi Infection

“…Therefore, the ideal treatment for T. cruzi should be capable of eliminating parasites with minimum or no toxicity and capable of mitigating the tissue damage in distinct organs caused by an exacerbated inflammatory response against parasite molecules. In the context of T. cruzi infection, our group has investigated the potential parasitological and immunomodulatory effects of drugs (e.g., enalapril maleate, simvastatin, beta-blocker, doxycycline) and naturally derived compounds (e.g., xanthenodiones and tetraketones) in a single therapy and/or in combination with Bz [ 9 , 24 , 38 , 39 ]. Supported by the promising data reflecting partial elimination of T. cruzi and modulation of the immune response (systemically and in infected tissues), our group has moved forward investigating curcumin and/or the submicron dispersed formulation of the curcumin, Theracurmin, in T. cruzi -infected mice.…”

Schistosoma mansoni Infection Is Impacted by Malnutrition

“…We used diets with restricted protein (3 or 8%) or lipid (2.5 or 5%) content based on the formulations proposed by American Institute of Nutrition (AIN) ( Reeves et al, 1993 ). AIN formulations are widely used in a variety of studies with different types of approaches ( Malafaia et al, 2009 ; Lemes et al, 2016 ; Souza et al, 2020 ). These formulations provide researchers a definition for maintaining consistency between studies, as well as enabling specific individual nutrient adjustment to meet different goals ( Pellizzon and Ricci, 2020 ).…”