Oxidative stress in chronic cardiopathy associated with Chagas disease

Oliveira, Tiago Bittencourt de; Pedrosa, Roberto Coury; Filho, Danilo Wilhelm

doi:10.1016/j.ijcard.2006.04.046

Cited by 73 publications

(70 citation statements)

References 41 publications

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“…Distinct plasma protein-nitrotyrosylation profiles have also been documented in acutelyand chronically-infected chagasic animals (24). These studies, along with documentation of oxidative overload in chagasic humans (25,26), support the idea that characterization of plasma proteomes will be useful in identifying the molecular mechanisms that are disturbed during the progression of Chagas disease.…”

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confidence: 72%

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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confidence: 72%

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

Wen

Garg

2012

Molecular & Cellular Proteomics

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“…This disease is characterized by cardiomegaly, ventricular dilation and arrhythmia, leading to HF (Rassi et al 2010). The antioxidant/oxidant imbalance was evident from increased plasma levels of glutathione disulfide and malonyldialdehyde (Wen et al 2006a), and decreased levels of glutathione (Wen et al 2006a;de Oliveira et al 2007) and glutathione peroxidise (Pérez-Fuentes et al 2003;de Oliveira et al 2007). In addition, increased levels of phospholipid oxidation products, protein carbonylation, and a heightened glutathione antioxidant defence (Wen et al 2004) have been shown to associate with oxidative overload in Chagas' disease (Wen et al 2006b).…”

Section: Titin As a Potential Biomarker In Chagas' Diseasementioning

confidence: 99%

A change of heart: oxidative stress in governing muscle function?

Breitkreuz

Hamdani

2015

Biophys Rev

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Redox/cysteine modification of proteins that regulate calcium cycling can affect contraction in striated muscles. Understanding the nature of these modifications would present the possibility of enhancing cardiac function through reversible cysteine modification of proteins, with potential therapeutic value in heart failure with diastolic dysfunction. Both heart failure and muscular dystrophy are characterized by abnormal redox balance and nitrosative stress. Recent evidence supports the synergistic role of oxidative stress and inflammation in the progression of heart failure with preserved ejection fraction, in concert with endothelial dysfunction and impaired nitric oxide-cyclic guanosine monophosphate-protein kinase G signalling via modification of the giant protein titin. Although antioxidant therapeutics in heart failure with diastolic dysfunction have no marked beneficial effects on the outcome of patients, it, however, remains critical to the understanding of the complex interactions of oxidative/nitrosative stress with pro-inflammatory mechanisms, metabolic dysfunction, and the redox modification of proteins characteristic of heart failure. These may highlight novel approaches to therapeutic strategies for heart failure with diastolic dysfunction. In this review, we provide an overview of oxidative stress and its effects on pathophysiological pathways. We describe the molecular mechanisms driving oxidative modification of proteins and subsequent effects on contractile function, and, finally, we discuss potential therapeutic opportunities for heart failure with diastolic dysfunction.

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“…The extent of protein modification in the heart and plasma of infected animals was correlated with the magnitude of inflammatory responses (13), which was suggestive of a role of inflammatory responses in sustaining oxidative/nitrosative stress during progressive Chagas' disease. In patients with Chagas' disease, enhanced oxidative stress (e.g., MDA, protein carbonyls, and glutathione disulfide) and a compromised antioxidant response (e.g., glutathione peroxidase and manganese superoxide dismutase activities, glutathione content) are noted in peripheral blood (41) and isolated erythrocytes (12). An increase in inflammatory cytokines (e.g., interleukin-10 [IL-10], IL-13, tumor necrosis factor alpha [TNF-␣], and gamma interferon) (15) and MPO activity (21) is also reported for patients with Chagas' disease.…”

Section: Vol 16 2009 Indicators Of Inflammation In Chagas' Disease 663mentioning

confidence: 99%

“…We have found increased plasma and cardiac levels of protein carbonyls and malonyldialdehydes (MDA; lipid peroxidation markers) in mice and rats infected by T. cruzi (13,40). A substantial increase in the plasma level of MDA, in association with inefficient glutathione antioxidant defense, has been documented for seropositive patients with Chagas' disease (12,41).…”

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confidence: 99%

Increased Myeloperoxidase Activity and Protein Nitration Are Indicators of Inflammation in Patients with Chagas' Disease

Dhiman

Estrada-Franco

Pando

et al. 2009

Clin Vaccine Immunol

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In this study, we investigated whether inflammatory responses contribute to oxidative/nitrosative stress in patients with Chagas' disease. We used three tests (enzyme-linked immunosorbent assay, immuno-flow cytometry, and STAT-PAK immunochromatography) to screen human serum samples (n ‫؍‬ 1,481) originating from Chiapas, Mexico, for Trypanosoma cruzi-specific antibodies. We identified 121 subjects who were seropositive for T. cruzi-specific antibodies, a finding indicative of an 8.5% seroprevalence in the rural population from Chiapas. Seropositive and seronegative subjects were examined for plasma levels of biomarkers of inflammation, i.e., myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), and xanthine oxidase (XOD), as well as for oxidative (advanced oxidation protein products [AOPPs]) and nitrosative (3-nitrotyrosine [3NT]) biomarkers. The seropositive subjects exhibited a significant increase in MPO activity and protein level, the indicator of neutrophil activation. Subsequently, a corresponding increase in AOPP contents, formed by MPO-dependent hypochlorous acid and chloramine formation, was noted in seropositive subjects. The plasma level of 3NT was significantly increased in seropositive subjects, yet we observed no change in XOD activity (O 2 ⅐ ؊ source) and nitrate/nitrite contents (denotes iNOS activation and ⅐ NO production), which implied that direct peroxynitrite formation does not contribute to increased nitrosative damage in chagasic subjects. Instead, a positive correlation between increased MPO activity and protein 3NT formation was observed, which suggested to us that MPO-dependent formation of nitrylchloride that occurs in the presence of physiological ⅐ NO and O 2 ⅐ ؊ concentrations contributes to protein nitration. Overall, our data demonstrate that T. cruzi-induced neutrophil activation is pathological and contributes to MPO-mediated collateral protein oxidative and nitrosative damage in human patients with Chagas' disease. Therapies capable of suppressing MPO activity may be useful in controlling the inflammation and oxidative/nitrosative pathology in chagasic cardiomyopathy.

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Oxidative stress in chronic cardiopathy associated with Chagas disease

Cited by 73 publications

References 41 publications

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

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

A change of heart: oxidative stress in governing muscle function?

Increased Myeloperoxidase Activity and Protein Nitration Are Indicators of Inflammation in Patients with Chagas' Disease

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