Antiproliferative effect of sera from chagasic patients on Trypanosoma cruzi epimastigotes. Involvement of xanthine oxidase

Hernández, Susana Muñoz; Kölliker-Frers, Rodolfo; Sánchez, Marcela; Razzitte, Gabriela; Britos, Rodny D.; Fuentes, María E.; Tarlovsky, Martha N. Schwarcz de

doi:10.1016/j.actatropica.2008.11.013

Cited by 6 publications

(5 citation statements)

References 26 publications

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“…The treatment of epimastigotes with this serum resulted in an inhibition of cell growth in vitro , a decrease in SOD activity, and an increase in membrane lipid peroxidation. Interestingly, the same results were not observed when parasites were treated with serum from healthy individuals [49]. Why epimastigotes have higher susceptibility to human serum than infective forms is unclear, but the exposure of epimastigotes to fresh human serum over a short period of time led to a decrease in cell respiration, loss of mitochondrial membrane potential, increased O 2 •− production, and release of cytochrome c , a process characteristic of programmed cell death [50].…”

Section: Differential Susceptibility Of T Cruzi Life Stages To Rosmentioning

confidence: 99%

The Role of Heme and Reactive Oxygen Species in Proliferation and Survival ofTrypanosoma cruzi

Paes

Cosentino-Gomes

Souza

et al. 2011

Journal of Parasitology Research

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Trypanosoma cruzi, the protozoan responsible for Chagas disease, has a complex life cycle comprehending two distinct hosts and a series of morphological and functional transformations. Hemoglobin degradation inside the insect vector releases high amounts of heme, and this molecule is known to exert a number of physiological functions. Moreover, the absence of its complete biosynthetic pathway in T. cruzi indicates heme as an essential molecule for this trypanosomatid survival. Within the hosts, T. cruzi has to cope with sudden environmental changes especially in the redox status and heme is able to increase the basal production of reactive oxygen species (ROS) which can be also produced as byproducts of the parasite aerobic metabolism. In this regard, ROS sensing is likely to be an important mechanism for the adaptation and interaction of these organisms with their hosts. In this paper we discuss the main features of heme and ROS susceptibility in T. cruzi biology.

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Section: Differential Susceptibility Of T Cruzi Life Stages To Rosmentioning

confidence: 99%

The Role of Heme and Reactive Oxygen Species in Proliferation and Survival ofTrypanosoma cruzi

Paes

Cosentino-Gomes

Souza

et al. 2011

Journal of Parasitology Research

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“…NADPH oxidase, activated in all phagocytic cells, produces superoxide (O 2 ⅐ Ϫ ) (1,11). Endothelial activation of xanthine oxidase (XOD) in response to T. cruzi infection also results in increased O 2 ⅐ Ϫ production via oxidation of hypoxanthine to xanthine and uric acid (3,17). Superoxide spontaneously recombines with other molecules to produce other free radicals (e.g., H 2 O 2 and ⅐ OH) that exert cytotoxic effects via modifications of DNA, protein, and lipids (7,23).…”

mentioning

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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“…This suggests that the complement system did not contribute to the inhibition of the invasion, an observation explained by the several strategies of evasion that T. cruzi presents against the complement [ 23 ]. The data of Hernandez and co-authors support the idea that an enhanced production of reactive oxygen species in chronically infected patients might contribute to the observed anti-parasitic effects of their sera [ 24 ]. It cannot be discarded that such a phenomenon, as well as other innate response factors, might play a certain role in the output of the currently described parasite inhibition assay.…”

Section: Discussionmentioning

confidence: 66%

Development and Application of an Assay to Evaluate the Anti-Parasitic Effect of Humoral Responses against Trypanosoma cruzi

et al. 2023

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Mounting a balanced and robust humoral immune response is of utmost importance for reducing the infectivity of Trypanosoma cruzi. While the role of such a response in controlling the infection is well known, there is a lack of tools that can be used to quickly evaluate it. We developed a serum parasite inhibition assay (to evaluate changes in the parasite infection after exposing infective T. cruzi trypomastigotes to serum samples from infected patients). It is based on Vero cells as the hosts and the Tulahuen β-galactosidase parasite strain, genetically engineered to be quantifiable by spectrophotometry. In parallel, we developed an in-house ELISA to correlate the anti-T. cruzi antibody titres of the clinical samples with their observed anti-parasitic effect in the serum parasite inhibition assay. Serum samples from chronically T. cruzi-infected patients significantly inhibited parasite invasion in a titre-dependant manner, regardless of the patient’s clinical status, compared to samples from the non-infected controls. In addition, there was a clear correlation between the reactivity of the samples to the whole-parasite lysates by ELISA and the inhibitory effect. The results of this work confirm the previously described anti-parasitic effect of the serum of individuals exposed to T. cruzi and present a framework for its large-scale evaluation in further studies. The serum parasite inhibition assay represents a reproducible way to evaluate the intensity and anti-parasitic effect of humoral responses against T. cruzi, which could be applied to the evaluation of candidate antigens/epitopes in the design of Chagas disease vaccine candidates.

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Antiproliferative effect of sera from chagasic patients on Trypanosoma cruzi epimastigotes. Involvement of xanthine oxidase

Cited by 6 publications

References 26 publications

The Role of Heme and Reactive Oxygen Species in Proliferation and Survival ofTrypanosoma cruzi

The Role of Heme and Reactive Oxygen Species in Proliferation and Survival ofTrypanosoma cruzi

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

Development and Application of an Assay to Evaluate the Anti-Parasitic Effect of Humoral Responses against Trypanosoma cruzi

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