The benefits of using selenium in the treatment of Chagas disease: prevention of right ventricle chamber dilatation and reversion of Trypanosoma cruzi-induced acute and chronic cardiomyopathy in mice

Souza, Andréa Pereira de; Jelicks, Linda A.; Tanowitz, Herbert B.; Olivieri, Bianca; Medeiros, Monica M.; Oliveira, Gabriel Melo de; Pires, Andrea; Santos, Alessandro M dos; Araújo-Jorge, Tânia C.

doi:10.1590/s0074-02762010000600003

Cited by 31 publications

(32 citation statements)

References 26 publications

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“…Other studies have demonstrated that ROS elicit inflammatory cytokines (e.g., TNF-␣, IFN-␥, and IL-1␤) in cardiomyocytes infected by T. cruzi (44,45). Inflammatory pathology was controlled in chronically infected experimental animals and human patients by enhancing the antioxidant status, which was also beneficial in preserving cardiac function during Chagas disease (15,16,46,47). Our recent observations indicate that the mitochondrial release of ROS caused by electron transport chain dysfunction and enhanced release of electrons to molecular oxygen is the primary source of oxidative stress in the heart (13).…”

Section: Discussionmentioning

confidence: 98%

Serum Proteomic Signature of Human Chagasic Patients for the Identification of Novel Potential Protein Biomarkers of Disease

Wen¹,

Zago

Nuñez³

et al. 2012

Molecular & Cellular Proteomics

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Chagas disease is initiated upon infection by Trypanosoma cruzi. Among the health consequences is a decline in heart function, and the pathophysiological mechanisms underlying this manifestation are not well understood. To explore the possible mechanisms, we employed IgY LC10 affinity chromatography in conjunction with ProteomeLab PF2D and two-dimensional gel electrophoresis to resolve the proteome signature of high and low abundance serum proteins in chagasic patients. MALDI-TOF MS/MS analysis yielded 80 and 14 differentially expressed proteins associated with cardiomyopathy of chagasic and other etiologies, respectively. The extent of oxidative stress-induced carbonyl modifications of the differentially expressed proteins (n ‫؍‬ 26) was increased and coupled with a depression of antioxidant proteins. Functional annotation of the top networks developed by ingenuity pathway analysis of proteome database identified dysregulation of inflammation/acute phase response signaling and lipid metabolism relevant to production of prostaglandins and arachidonic acid in chagasic patients. Overlay of the major networks identified prothrombin and plasminogen at a nodal position with connectivity to proteome signature indicative of heart disease (i.e., thrombosis, angiogenesis, vasodilatation of blood vessels or the aorta, and increased permeability of blood vessel and endothelial tubes), and inflammatory responses (e.g., platelet aggregation, complement activation, and phagocyte activation and migration). The detection of cardiac proteins (myosin light chain 2 and myosin heavy chain 11) and increased levels of vinculin and plasminogen provided a comprehensive set of biomarkers of cardiac muscle injury and development of clinical Chagas disease in human patients. These results provide an impetus for biomarker validation in large cohorts of clinically characterized chagasic patients. Molecular & Cellular

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Section: Discussionmentioning

confidence: 98%

Serum Proteomic Signature of Human Chagasic Patients for the Identification of Novel Potential Protein Biomarkers of Disease

Wen¹,

Zago

Nuñez³

et al. 2012

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

show abstract

“…trolled in chronically infected experimental animals and human patients by enhancing the antioxidant status, which was also beneficial in preserving the cardiac function during Chagas disease (18,23,38,39). Our recent observations indicate that the mitochondrial release of ROS because of electron transport chain dysfunction and enhanced release of electrons to molecular oxygen is the primary source of oxidative stress in the heart (21).…”

Section: Idmentioning

confidence: 94%

Proteome Expression and Carbonylation Changes During Trypanosoma cruzi Infection and Chagas Disease in Rats

Wen

Garg

2012

Molecular & Cellular Proteomics

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Inflammation and oxidative stress, elicited by Trypanosoma cruzi infection, are important pathologic events during progressive Chagasic cardiomyopathy. In this study, we infected Sprague-Dawley rats with T. cruzi, and treated with phenyl-␣-tert-butylnitrone (PBN-antioxidant) and/or benznidazole (BZ-anti-parasite). We employed two-dimensional gel electrophoresis/mass spectrometry to investigate (a) the plasma proteomic changes associated with infection and disease development, and (b) the beneficial effects of PBN and BZ in controlling the disease-associated plasma profile. Matrix-assisted laser desorption ionization/time of flight (MALDI-TOF) tandem MS (MS/MS) analysis of differentially expressed (total 146) and oxidized (total 48) protein spots yielded 92 unique proteins. Our data showed that treatment with PBN and BZ restored the differential expression of 65% and 30% of the disease-associated proteins to normal level, respectively, and PBN prevented development of oxidative adducts on plasma proteins. Western blotting to detect dinitrophenyl-derivatized carbonyl-proteins revealed plasma proteins were maximally oxidized during acute infection. Functional and disease/disorder analyses allocated a majority of the differentially expressed and oxidized proteins into inflammation/immunity and lipid metabolism categories and to molecular pathways associated with heart disease (e.g. cardiac infarction, contractile dysfunction, hypertrophy, and hypertension) in chagasic rats, and to curative pathways (e.g. ROS scavenging capacity, immune regulation) in infected rats treated with PBN and/or BZ. We validated the two-dimensional gel electrophoresis results by Western blotting, and demonstrated that the disease-associated increased expression of gelsolin and vimentin and release of cardiac MYL2 in the plasma of chagasic rats was returned to control level by PBN/BZ treatment. Increased plasma levels of gelsolin, MYL2 and vimentin were directly correlated with the severity of cardiac disease in human chagasic patients. Together, these results demonstrate the plasma oxidative and inflammatory response profile, and plasma detection of cardiac proteins parallels the pathologic events contributing to Chagas disease development,

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“…reactivity to stimuli and hair cleanliness) as compared to those infected with WT parasites. At this point it is worth to mention that selenium supplementation has been shown to contribute to control parasitemia in various trypanosome infections and to improve several disease-associated symptoms such as anemia and organ damage [37][38][39]. Although the mechanism by which selenium counteracts trypanosome-induced pathogenesis remains elusive, it is tempting to speculate that the improved phenotype of mice infected with parasites deficient in selenoproteins stem from a larger availability of selenium by the host due to a lower demand by the mutant pathogen.…”

Section: Selenoproteins Are Fully Dispensable For the Survival Of Afrmentioning

confidence: 99%

Selenoproteins of African trypanosomes are dispensable for parasite survival in a mammalian host

Bonilla

Krull

Irigoı́n

et al. 2016

Molecular and Biochemical Parasitology

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The benefits of using selenium in the treatment of Chagas disease: prevention of right ventricle chamber dilatation and reversion of Trypanosoma cruzi-induced acute and chronic cardiomyopathy in mice

Abstract: Cardiac damage is a frequent manifestation of Chagas disease, which is caused by the parasite

Cited by 31 publications

References 26 publications

Serum Proteomic Signature of Human Chagasic Patients for the Identification of Novel Potential Protein Biomarkers of Disease

Serum Proteomic Signature of Human Chagasic Patients for the Identification of Novel Potential Protein Biomarkers of Disease

Proteome Expression and Carbonylation Changes During Trypanosoma cruzi Infection and Chagas Disease in Rats

Selenoproteins of African trypanosomes are dispensable for parasite survival in a mammalian host

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