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

Horta, Aline Luciano; Leite, Ana; Costa, G.; Figueiredo, Vivian Paulino

doi:10.1155/2017/9205062

Cited by 7 publications

(6 citation statements)

References 43 publications

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“… 7 , 12 In particular, our group has recently observed that Cv therapy in mice infected with the VL-10 strain of T. cruzi was capable to reduce the plasma levels of the CCL2 chemokine and to elevate the levels of IL-10 reflecting in the reduction of the inflammatory process in the cardiac tissue. 13 However, opposing our expectancies, the current results using the inflammatory strain of the T. cruzi (Colombian strain) implied that Cv therapy worsened T. cruzi infection course in the murine model, enhancing mortality rate, parasitaemia, and leukocyte infiltration as well as increasing the circulating levels of inflammatory chemokines.…”

Section: Discussioncontrasting

confidence: 73%

The β-blocker carvedilol and the benznidazole modulate the cardiac immune response in the acute infection induced by Colombian strain of the Trypanosoma cruzi

Horta

Figueiredo

Leite

et al. 2018

Mem. Inst. Oswaldo Cruz

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BACKGROUND The infection led by Trypanosoma cruzi persists in mammalian tissues causing an inflammatory imbalance. Carvedilol (Cv), a non-selective beta blocker drug indicated to treat heart failure and antihypertensive has shown to promote antioxidant and immunomodulatory properties which might improve the inflammation induced by T. cruzi. OBJECTIVES Evaluate the role of Cv on the inflammatory response of C57BL/6 mice acutely infected with the Colombian strain of T. cruzi. METHODS Animals were infected with the Colombian strain of T. cruzi and treated with Cv (25 mg/kg/day), benznidazole (Bz) (100 mg/kg/day) or their combination. On the 28th day of infection and 23 days of treatment, the euthanasia occurred, and the heart preserved for histopathological, oxidative stress (SOD, catalase, TBARs, carbonylated proteins) and plasma (CCL2, CCL5, TNF, IL-10) analyses. Parasitaemia and survival were assessed along the infection. FINDINGS Cv decreased TBARs, but increased the mortality rate, the parasitaemia and the levels of CCL2, CCL5, catalase and the inflammatory infiltrate in the cardiac tissue. Bz led the reduction of the inflammatory infiltrate and circulating levels of oxidative stress and inflammatory mediators in the infected mice. MAIN CONCLUSIONS Our data suggest that Cv, in this experimental model using the Colombian strain of T. cruzi, caused damage to the host.

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Section: Discussioncontrasting

confidence: 73%

The β-blocker carvedilol and the benznidazole modulate the cardiac immune response in the acute infection induced by Colombian strain of the Trypanosoma cruzi

Horta

Figueiredo

Leite

et al. 2018

Mem. Inst. Oswaldo Cruz

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“…Our group has investigated the use of different medicines in clinical practice (simvastatin, doxycycline, angiotensin-enzyme converter inhibitor, beta-blocker, and others) alone or in association with benznidazole to reduce the release of cytokines IFN-g, TNF, IL-6, IL-10 and chemokines (CCL2, CCL3, CCL4, CCL5, CXCL9, CXCL11, CCL1, CCL17, CCL20, CCL24, and CCL26) and minimize inflammatory infiltration into the heart, which is important to ameliorate the consequences of T. cruzi antigens. However, these events trigger fibrosis formation and cardiac morphological and functional damage (Silva et al, 2012;de Paula Costa et al, 2016;Horta et al, 2017;Leite et al, 2017). These cytokines can shift the regulation patterns described during the acute and chronic courses of T. cruzi infection, affecting the parasite-host equilibrium and driving the pathogenesis process (Talvani and Teixeira, 2011).…”

Section: Discussionmentioning

confidence: 99%

New Insights Into Blue Light Phototherapy in Experimental Trypanosoma cruzi Infection

Иванова

Leite

Vieira

et al. 2021

Front. Cell. Infect. Microbiol.

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The search for an effective etiologic treatment to eliminate Trypanosoma cruzi, the causative agent of Chagas disease, has continued for decades and yielded controversial results. In the 1970s, nifurtimox and benznidazole were introduced for clinical assessment, but factors such as parasite resistance, high cellular toxicity, and efficacy in acute and chronic phases of the infection have been debated even today. This study proposes an innovative strategy to support the controlling of the T. cruzi using blue light phototherapy or blue light-emitting diode (LED) intervention. In in vitro assays, axenic cultures of Y and CL strains of T. cruzi were exposed to 460 nm and 40 µW/cm2 of blue light for 5 days (6 h/day), and parasite replication was evaluated daily. For in vivo experiments, C57BL6 mice were infected with the Y strain of T. cruzi and exposed to 460 nm and 7 µW/cm2 of blue light for 9 days (12 h/day). Parasite count in the blood and cardiac tissue was determined, and plasma interleukin (IL-6), tumoral necrosis factor (TNF), chemokine ligand 2 (CCL2), and IL-10 levels and the morphometry of the cardiac tissue were evaluated. Blue light induced a 50% reduction in T. cruzi (epimastigote forms) replication in vitro after 5 days of exposure. This blue light-mediated parasite control was also observed by the T. cruzi reduction in the blood (trypomastigote forms) and in the cardiac tissue (parasite DNA and amastigote nests) of infected mice. Phototherapy reduced plasma IL-6, TNF and IL-10, but not CCL2, levels in infected animals. This non-chemical therapy reduced the volume density of the heart stroma in the cardiac connective tissue but did not ameliorate the mouse myocarditis, maintaining a predominance of pericellular and perivascular mononuclear inflammatory infiltration with an increase in polymorphonuclear cells. Together, these data highlight, for the first time, the use of blue light therapy to control circulating and tissue forms of T. cruzi. Further investigation would demonstrate the application of this promising and potential complementary strategy for the treatment of Chagas disease.

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“…Carvedilol has also been shown to decrease the production of ROS, such as H 2 O 2 , which is responsible for driving calcium overload in HF [ 24 ]. In a study on experimental infection with Trypanosoma cruzi , carvedilol decreased CCL2 levels and increased the levels of the anti-inflammatory cytokine IL-10, resulting in decreased inflammatory infiltration in cardiac muscle [ 25 ].…”

Section: β-Blockersmentioning

confidence: 99%

Immunopharmacology of Post-Myocardial Infarction and Heart Failure Medications

Panahi

Vadgama

Kuganesan

et al. 2018

JCM

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The immune system responds to acute tissue damage after myocardial infarction (MI) and orchestrates healing and recovery of the heart. However, excessive inflammation may lead to additional tissue damage and fibrosis and exacerbate subsequent functional impairment, leading to heart failure. The appreciation of the immune system as a crucial factor after MI has led to a surge of clinical trials investigating the potential benefits of immunomodulatory agents previously used in hyper-inflammatory conditions, such as autoimmune disease. While the major goal of routine post-MI pharmacotherapy is to support heart function by ensuring appropriate blood pressure and cardiac output to meet the demands of the body, several drug classes also affect a range of immunological pathways and modulate the post-MI immune response, which is crucial to take into account when designing future immunomodulatory trials. This review outlines how routine post-MI pharmacotherapy affects the immune response and may thus influence post-MI outcomes and development towards heart failure. Current key drug classes are discussed, including platelet inhibitors, statins, β-blockers, and renin–angiotensin–aldosterone inhibitors.

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

Cited by 7 publications

References 43 publications

The β-blocker carvedilol and the benznidazole modulate the cardiac immune response in the acute infection induced by Colombian strain of the Trypanosoma cruzi

The β-blocker carvedilol and the benznidazole modulate the cardiac immune response in the acute infection induced by Colombian strain of the Trypanosoma cruzi

New Insights Into Blue Light Phototherapy in Experimental Trypanosoma cruzi Infection

Immunopharmacology of Post-Myocardial Infarction and Heart Failure Medications

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