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

Trypanosoma cruzi infection induces progressive cardiac inflammation that leads to fibrosis and modifications in the heart architecture and functionality. Statins, such as 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, have been studied due to their pleiotropic roles in modulating the inflammatory response. Our goal was to evaluate the effects of simvastatin on the cardiac inflammatory process using a cardiotropic strain of T. cruzi in a murine model of Chagas cardiomyopathy. C57BL/6 mice were infected with 500 trypomastigotes of the Colombian strain of T. cruzi and treated with an oral dose of simvastatin (20 mg/Kg/day) for one month and inflammatory and morphometric parameters were subsequently evaluated in the serum and in the heart, respectively. Simvastatin reduced the total cholesterol and inflammatory mediators (interferon-gamma, tumour necrosis factor-alpha, CCL2 and CCL5) in the serum and in the heart tissue at 30 days post-infection. Additionally, a proportional reduction in heart weight and inflammatory infiltration was observed. Simvastatin also reduced epimastigote proliferation in a dose-dependent manner in vitro and was able to reduce blood trypomastigotes and heart amastigote nests during the acute phase of Chagas disease in vivo. Based on these data, we conclude that simvastatin exerts a modulatory effect on the inflammatory mediators that are elicited by the Colombian strain of T. cruzi and ameliorates the heart damage that is observed in a murine model of Chagas disease.

• Publication year

  2012

• Venue

  Memórias do Instituto Oswaldo Cruz

• Publication date

  2012-06-01

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1590/S0074-02762012000400012PMID 22666863
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• [Chagas disease (American trypanosomiasis) in France].

  2012cited by this paper
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  2011cited by this paper
• Mechanisms for the anti-inflammatory effects of statins

  2011cited by this paper
• Inflammation and Chagas disease some mechanisms and relevance.

  2011cited by this paper
• Inflammation and the development of atherosclerosis.

  2011cited by this paper
• Evaluation of Biological and Biochemical Quality of Whey Protein

  2010cited by this paper
• Captopril increases the intensity of monocyte infection by Trypanosoma cruzi and induces human T helper type 17 cells

  2010cited by this paper
• Benznidazole alters the pattern of Cyclophosphamide-induced reactivation in experimental Trypanosoma cruzi-dependent lineage infection.

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• Statins and inflammation: an update

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• Increased type 1 chemokine expression in experimental Chagas disease correlates with cardiac pathology in beagle dogs.

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• Enalapril prevents cardiac immune‐mediated damage and exerts anti‐Trypanosoma cruzi activity during acute phase of experimental Chagas disease

  2010cited by this paper
• Plasma concentrations of tumour necrosis factor‐alpha, tumour necrosis factor‐related apoptosis‐inducing ligand, and FasLigand/CD95L in patients with Chagas cardiomyopathy correlate with left ventricular dysfunction

  2009cited by this paper
• Treatment of chronically Trypanosoma cruzi-infected mice with a CCR1/CCR5 antagonist (Met-RANTES) results in amelioration of cardiac tissue damage.

  2009cited by this paper
• CCL2/MCP‐1 controls parasite burden, cell infiltration, and mononuclear activation during acute Trypanosoma cruzi infection

  2009cited by this paper
• Ergosterol biosynthesis and drug development for Chagas disease.

  2009cited by this paper
• Chemokine, vascular and therapeutic effects of combination Simvastatin and BMSC treatment of stroke.

  2009cited by this paper
• Chronic Trypanosoma cruzi-elicited cardiomyopathy: from the discovery to the proposal of rational therapeutic interventions targeting cell adhesion molecules and chemokine receptors--how to make a dream come true.

  2009cited by this paper
• The effect of simvastatin on the serum monocyte chemoattractant protein-1 and intracellular adhesion molecule-1 levels in diabetic rats.

  2009cited by this paper
• Trypanosoma cruzi: participation of cholesterol and placental alkaline phosphatase in the host cell invasion.

  2009cited by this paper
• A new consensus for Trypanosoma cruzi intraspecific nomenclature: second revision meeting recommends TcI to TcVI.

  2009cited by this paper
• Mechanisms of myocardial damage in Trypanosoma cruzi infection.

  2008cited by this paper
• Benznidazole therapy during acute phase of Chagas disease reduces parasite load but does not prevent chronic cardiac lesions

  2008cited by this paper
• Inhibition of chemokine receptor CCR2 and CCR5 expression contributes to simvastatin-induced attenuation of cardiac allograft vasculopathy.

  2007cited by this paper
• A randomized trial of carvedilol after renin-angiotensin system inhibition in chronic Chagas cardiomyopathy.

  2007cited by this paper
• Statins and biomarkers of inflammation

  2007cited by this paper
• Macrophage infiltration, lectin-like oxidized-LDL receptor-1, and monocyte chemoattractant protein-1 are reduced by chronic HMG-CoA reductase inhibition.

  2007cited by this paper
• Statins Disrupt CCR5 and RANTES Expression Levels in CD4+ T Lymphocytes In Vitro and Preferentially Decrease Infection of R5 Versus X4 HIV-1

  2007cited by this paper
• Trypanosoma cruzi strains isolated from human, vector, and animal reservoir in the same endemic region in Mexico and typed as T. cruzi I, discrete typing unit 1 exhibit considerable biological diversity.

  2006cited by this paper
• The CC Chemokine Receptor 5 Is Important in Control of Parasite Replication and Acute Cardiac Inflammation following Infection with Trypanosoma cruzi

  2006cited by this paper
• Low-dose simvastatin improves survival and ventricular function via eNOS in congestive heart failure.

  2006cited by this paper
• Upregulation of sterol C14-demethylase expression in Trypanosoma cruzi treated with sterol biosynthesis inhibitors.

  2005cited by this paper
• Effects of Atorvastatin on Th polarization in patients with acute myocardial infarction

  2005cited by this paper
• CCR5 Plays a Critical Role in the Development of Myocarditis and Host Protection in Mice Infected with Trypanosoma cruzi

  2005cited by this paper
• The effects of statins on endothelium, inflammation and cardioprotection.

  2005cited by this paper
• Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) Antagonist (Met-RANTES) Controls the Early Phase of Trypanosoma cruzi–Elicited Myocarditis

  2004cited by this paper
• Captopril Ameliorates Myocarditis in Acute Experimental Chagas Disease

  2003cited by this paper
• Short-Term Statin Therapy Improves Cardiac Function and Symptoms in Patients With Idiopathic Dilated Cardiomyopathy

  2003cited by this paper
• Isoprenoids as mediators of the biological effects of statins.

  2002cited by this paper
• Kinetic properties and inhibition of Trypanosoma cruzi 3‐hydroxy‐3‐methylglutaryl CoA reductase

  2002cited by this paper
• Chemokines, inflammation and Trypanosoma cruzi infection.

  2002cited by this paper
• Clinical and epidemiological aspects of Chagas disease.

  2001cited by this paper
• Effect of simvastatin on monocyte adhesion molecule expression in patients with hypercholesterolemia.

  2001cited by this paper
• Kinetics of cytokine gene expression in experimental chagasic cardiomyopathy: tissue parasitism and endogenous IFN-gamma as important determinants of chemokine mRNA expression during infection with Trypanosoma cruzi.

  2000cited by this paper
• β-Chemokines Enhance Parasite Uptake and Promote Nitric Oxide-Dependent Microbiostatic Activity in Murine Inflammatory Macrophages Infected with Trypanosoma cruzi

  1999cited by this paper
• beta-Chemokines enhance parasite uptake and promote nitric oxide-dependent microbiostatic activity in murine inflammatory macrophages infected with Trypanosoma cruzi.

  1999cited by this paper
• Immunological control of Trypanosoma cruzi infection and pathogenesis of Chagas' disease.

  1997cited by this paper
• Characterization of inflammatory infiltrates in chronic chagasic myocardial lesions: presence of tumor necrosis factor-alpha+ cells and dominance of granzyme A+, CD8+ lymphocytes.

  1993cited by this paper
• Mevinolin (lovastatin) potentiates the antiproliferative effects of ketoconazole and terbinafine against Trypanosoma (Schizotrypanum) cruzi: in vitro and in vivo studies

  1993influential reference
• Inhibition of Trypanosoma cruzi growth and sterol biosynthesis by lovastatin.

  1990cited by this paper
• Verapamil ameliorates clinical, pathologic and biochemical manifestations of experimental chagasic cardiomyopathy in mice.

  1989cited by this paper
• Mitral Incompetence Caused by Disease of the Mural Cusp

  1959cited by this paper

• Statins do not reduce the parasite burden during experimental Trypanosoma cruzi infection

  2025cites this paper
• Unveiling Lovastatin’s Anti-Inflammatory Potential in Mouse’s Brain during Acute Trypanosoma cruzi Infection

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• Biosynthesis of ergosterol as a relevant molecular target of metal-based antiparasitic and antifungal compounds

  2024cites this paper
• Antiplasmodial, Trypanocidal, and Genotoxicity In Vitro Assessment of New Hybrid α,α-Difluorophenylacetamide-statin Derivatives

  2023cites this paper
• Statin and aspirin use in parasitic infections as a potential therapeutic strategy: A narrative review.

  2023cites this paper
• Resveratrol and Curcumin for Chagas Disease Treatment—A Systematic Review

  2022cites this paper
• Repurposing non-antimicrobial drugs for treatment of staphylococcal infections

  2021cites this paper
• New Insights Into Blue Light Phototherapy in Experimental Trypanosoma cruzi Infection

  2021cites this paper
• A High-Fat Diet Exacerbates the Course of Experimental Trypanosoma cruzi Infection That Can Be Mitigated by Treatment with Simvastatin

  2020cites this paper
• Combination therapy with benznidazole and doxycycline shows no additive effect to monotherapy with benznidazole in mice infected with the VL-10 strain of the Trypanosoma cruzi.

  2020cites this paper
• Are the Statins promising antifungal agents against invasive candidiasis?

  2019cites this paper
• Chagas Disease: Past, Present, and Future

  2019cites this paper
• Lycopene mitigates pulmonary emphysema induced by cigarette smoke in a murine model.

  2019cites this paper
• Chapter 9 New Approaches for Chagas ’ Disease Chemotherapy

  2018cites this paper
• Repurposing Strategy of Atorvastatin against Trypanosoma cruzi: In Vitro Monotherapy and Combined Therapy with Benznidazole Exhibit Synergistic Trypanocidal Activity

  2018cites this paper
• High fat diet modulates inflammatory parameters in the heart and liver during acute Trypanosoma cruzi infection

  2018cites this paper
• New Approaches for Chagas’ Disease Chemotherapy

  2018cites this paper
• The antioxidant and anti-inflammatory properties of lycopene in mice lungs exposed to cigarette smoke.

  2017cites this paper
• Influence of environmental enrichment on the behavior and physiology of mice infected by Trypanosoma cruzi.

  2017cites this paper
• Potential Role of Carvedilol in the Cardiac Immune Response Induced by Experimental Infection with Trypanosoma cruzi

  2017cites this paper
• Activity of rosuvastatin in tachyzoites of Toxoplasma gondii (RH strain) in HeLa cells.

  2017cites this paper
• Repurposing non-antimicrobial drugs to treat multi-drug resistant bacterial and fungal infections

  2016cites this paper
• The Effects of the Combination of a Refined Carbohydrate Diet and Exposure to Hyperoxia in Mice

  2016cites this paper
• Sterol Biosynthesis Pathway as an Alternative for the Anti-Protozoan Parasite Chemotherapy.

  2015cites this paper
• Drug repurposing for the treatment of staphylococcal infections.

  2015cites this paper
• Enalapril in Combination with Benznidazole Reduces Cardiac Inflammation and Creatine Kinases in Mice Chronically Infected with Trypanosoma cruzi.

  2015cites this paper
• Simvastatin and Benznidazole-Mediated Prevention of Trypanosoma cruzi-Induced Endothelial Activation: Role of 15-epi-lipoxin A4 in the Action of Simvastatin

  2015cites this paper
• View of statins as antimicrobials in cardiovascular risk modification.

  2014cites this paper
• Production and expression of inflammation and angiogenic parameters triggered by different genetic population of Trypanosoma cruzi

  2014influential citation
• Viewofstatinsasantimicrobials incardiovascularrisk modification

  2014cites this paper
• Genome profiling of sterol synthesis shows convergent evolution in parasites and guides chemotherapeutic attack

  2014cites this paper