Nox2-derived superoxide radical is crucial to control acute Trypanosoma cruzi infection

Prolo, Carolina; Estrada, Damián; Piacenza, Lucı́a; Benítez, Diego; Comini, Marcelo A.; Radí, Rafael; Álvarez, María Noel

doi:10.1016/j.redox.2021.102085

Cited by 8 publications

(7 citation statements)

References 69 publications

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“…In addition, the pathway contributes to the generation of second derivatives of ROS such as hydrogen peroxide, which, at high concentrations, promote critical oxidative modifications (48)(49)(50).…”

Section: Discussionmentioning

confidence: 99%

Predicting Blood Parasite Load and Influence of Expression of iNOS on the Effect Size of Clinical Laboratory Parameters in Acute Trypanosoma cruzi Infection With Different Inoculum Concentrations in C57BL/6 Mice

et al. 2022

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In Chagas disease, the initial responses of phagocyte-mediated innate immunity are strongly associated with the control of Trypanosoma cruzi and are mediated by various signaling pathways, including the inducible nitric oxide synthetase (iNOS) pathway. The clinical and laboratory manifestations of Chagas disease depend on the parasite–host relationship, i.e., the responsive capacity of the host immune system and the immunogenicity of the parasite. Here, we evaluated effect sizes in clinical and laboratory parameters mediated by acute infection with different concentrations of T. cruzi inoculum in mice immunosuppressed via iNOS pathway inactivation. Infection was induced in C57BL/6 wild-type and iNOS-/- mice with the “Y” strain of T. cruzi at three inoculum concentrations (3 × 102, 3 × 103, and 3 × 104). Parasitemia and mortality in both mouse strains were monitored. Immunohistochemistry was performed to quantify amastigotes in cardiac tissues and cardiac musculature cells. Biochemical parameters, such as blood urea nitrogen, sodium, albumin, and globulin concentrations, among others, were measured, and cytokine concentrations were also measured. Effect sizes were determined by the eta squared formula. Compared with that in wild-type animals, mice with an absence of iNOS expression demonstrated a greater parasite load, with earlier infection and a delayed parasitemia peak. Inoculum concentration was positively related to death in the immunosuppressed subgroup. Nineteen parameters (hematological, biochemical, cytokine-related, and histopathological) in the immunocompetent subgroup and four in the immunosuppressed subgroup were associated with parasitemia. Parasitemia, biochemical parameters, and hematological parameters were found to be predictors in the knockout group. The impact of effect sizes on the markers evaluated based on T. cruzi inoculum concentration was notably high in the immunocompetent group (Cohen’s d = 88.50%; p <.001). These findings contribute to the understanding of physiopathogenic mechanisms underlying T. cruzi infection and also indicate the influence of the concentration of T. cruzi during infection and the immunosuppression through the iNOS pathway in clinical laboratory heterogeneity reported in acute Chagas disease.

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Section: Discussionmentioning

confidence: 99%

Predicting Blood Parasite Load and Influence of Expression of iNOS on the Effect Size of Clinical Laboratory Parameters in Acute Trypanosoma cruzi Infection With Different Inoculum Concentrations in C57BL/6 Mice

et al. 2022

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“…[47] It is significant to note that Nox proteins not only maintain various structural homologies, but they also produce different ROS as well. For instance, Nox1 and Nox2 result in O 2 *À generation, [48] Nox4 generate H 2 O 2 , [49] and Nox5 contribute to calcium-dependent H 2 O 2 generation. [50] ROS production by NOX is implicated in various physiological and pathophysiological processes, such as hearing loss, blood pressure responses, and inflammation.…”

Section: Nadph Enzymes Related Organellesmentioning

confidence: 99%

Recent Advances in Detection of Hydroxyl Radical by Responsive Fluorescence Nanoprobes

Alanazi,

Yong,

et al. 2024

Chemistry An Asian Journal

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Hydroxyl radical (•OH), a highly reactive oxygen species (ROS), is assumed as one of the most aggressive free radicals. This radical has a detrimental impact on cells as it can react with different biological substrates leading to pathophysiological disorders, including inflammation, mitochondrion dysfunction, and cancer. Quantification of this free radical in‐situ plays critical roles in early diagnosis and treatment monitoring of various disorders, like macrophage polarization and tumor cell development. Luminescence analysis using responsive probes has been an emerging and reliable technique for in‐situ detection of various cellular ROS, and some recently developed •OH responsive nanoprobes have confirmed the association with cancer development. This paper aims to summarize the recent advances in the characterization of •OH in living organisms using responsive nanoprobes, covering the production, the sources of •OH, and biological function, especially in the development of related diseases followed by the discussion of luminescence nanoprobes for •OH detection.

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“… 37 Importantly, NOX2 is fundamental to global ROS generation in cardiomyocytes during stress conditions, 49 and this enzyme is a relevant source of ROS during T. cruzi infection. 50 …”

Section: Electrical Remodeling In Ccmmentioning

confidence: 99%

Arrhythmogenic Manifestations of Chagas Disease: Perspectives From the Bench to Bedside

Roman-Campos,

Marin-Neto,

Santos-Miranda

et al. 2024

Circulation Research

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Chagas cardiomyopathy caused by infection with the intracellular parasite Trypanosoma cruzi is the most common and severe expression of human Chagas disease. Heart failure, systemic and pulmonary thromboembolism, arrhythmia, and sudden cardiac death are the principal clinical manifestations of Chagas cardiomyopathy. Ventricular arrhythmias contribute significantly to morbidity and mortality and are the major cause of sudden cardiac death. Significant gaps still exist in the understanding of the pathogenesis mechanisms underlying the arrhythmogenic manifestations of Chagas cardiomyopathy. This article will review the data from experimental studies and translate those findings to draw hypotheses about clinical observations. Human- and animal-based studies at molecular, cellular, tissue, and organ levels suggest 5 main pillars of remodeling caused by the interaction of host and parasite: immunologic, electrical, autonomic, microvascular, and contractile. Integrating these 5 remodeling processes will bring insights into the current knowledge in the field, highlighting some key features for future management of this arrhythmogenic disease.

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Nox2-derived superoxide radical is crucial to control acute Trypanosoma cruzi infection

Cited by 8 publications

References 69 publications

Predicting Blood Parasite Load and Influence of Expression of iNOS on the Effect Size of Clinical Laboratory Parameters in Acute Trypanosoma cruzi Infection With Different Inoculum Concentrations in C57BL/6 Mice

Predicting Blood Parasite Load and Influence of Expression of iNOS on the Effect Size of Clinical Laboratory Parameters in Acute Trypanosoma cruzi Infection With Different Inoculum Concentrations in C57BL/6 Mice

Recent Advances in Detection of Hydroxyl Radical by Responsive Fluorescence Nanoprobes

Arrhythmogenic Manifestations of Chagas Disease: Perspectives From the Bench to Bedside

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