20 research outputs found

    The Journey of <em>Trypanosoma cruzi</em> under the Redox Baton

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    Trypanosoma cruzi is a protozoan responsible for Chagas disease and has a complex life cycle including vertebrate (mammals) and invertebrate (insects) hosts. The parasite presents proliferative and infective forms that are challenged throughout their cycle as different sources of nutrients, pH, immune system, and levels of reactive oxygen species (ROS). Although ROS cause damage to cells and tissues when their levels are controlled, they are involved in signal transduction pathways involved in cell growth and differentiation. Curiously, the proliferation of epimastigote inside the bug insect is favored by high levels of ROS from the digestion of blood meal, and it is regulated by a cellular signaling mechanism involving heme and CaMKII. On the other hand, the differentiation of epimastigote into metacyclic trypomastigote in the rectum occurs in the reduced state. Interestingly, when the parasite infects the vertebrate, the immune system recognizes this pathogen and macrophages become activated. Thus, NADPH oxidase produces ROS that helps the parasite enter the mammalian cells, improving the infection. The parasite thrives inside the mammalian cells also involving ROS. Thus, the life cycle of Trypanosoma cruzi obeys a fine tuning of the redox state, not affecting the host cells and being helpful to the parasite

    Análise espacial do tráfico de aves silvestres no estado de Pernambuco, Brasil

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    Wild animal trafficking is a growing practice worldwide and a complex problem that brings a lot of profit, moving billions of dollars. This illegal trade has Brazil as route due to its rich biodiversity. It is widespread throughout the state of Pernambuco, having constant growth because the state is in a geographical position that favors this type of illegal practice and has a great diversity of species. Thus, the objective of the study was to perform a spatial analysis of wild bird trafficking in the municipalities of the state of Pernambuco in the period from 2016 to 2021, through an exploratory data analysis with seven variables that could explain its occurrence. It was used as methodology the global and local Moran’s indexes, all implemented in the Geographic Information System software. The findings revealed that the municipalities that showed high average rates of wild bird trafficking in the investigated period, in general, are geographically close to those that also showed high rates of seizure of birds, Intentional Lethal Violent Crime, Violent Crime against Property, and unemployment. In general, the results allowed us to conclude that the methods of spatial cluster analysis proved satisfactory for the analysis in question. Moreover, it is important to note that the precarious enforcement favors the continuity of this practice, and there is an urgent need for environmental policies to restrain it effectively.O tráfico de animais silvestres é uma prática crescente em todo o mundo e um problema de difícil solução que traz bastante lucro, movimentando bilhões de dólares. Esse mercado tem o Brasil como rota por possuir rica biodiversidade. O comércio ilegal é amplo em todo o estado de Pernambuco, tendo crescimento constante por estar o estado em posição geográfica que favorece esse tipo de prática ilegal e possuir grande diversidade de espécies. Dessa forma, o objetivo do estudo foi realizar uma análise espacial do tráfico de aves silvestres nos municípios do estado de Pernambuco no período de 2016 a 2021, por meio de uma análise exploratória de dados com sete variáveis que pudessem explicar sua ocorrência. Foram utilizados como metodologia os índices de Moran global e local, todos implementados no software de Sistema de Informação Geográfica. Os resultados revelaram que os municípios que apresentaram altas taxas médias de tráfico de aves silvestres no período investigado, de maneira geral, encontram-se geograficamente próximos daqueles que também demonstraram elevadas taxas de apreensão de aves, taxas de crime violento letal intencional, taxas de crime violento contra o patrimônio e taxa de desemprego. De maneira geral, os resultados permitiram concluir que os métodos de análise espacial de agrupamentos se mostraram satisfatórios para a análise em questão. Além disso, é importante salientar que a fiscalização precária favorece a continuidade dessa prática, havendo necessidade de políticas ambientais com o objetivo de coibir tal prática de forma efetiva

    High incidence of acquiring methicillin-resistant <i>Staphylococcus aureus</i> in Brazilian children with Atopic Dermatitis and associated risk factors

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    BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) colonization in Atopic Dermatitis (AD) patients can contribute to worsening their clinical condition. OBJECTIVE: A cohort study was carried out to determine the incidence of MRSA acquisition and its risk factors in AD children. METHODS: Patients with AD (2 months-14 years old) were followed up for about 1 year at a reference center for AD treatment in Rio de Janeiro, Brazil, from September 2011 to February 2014. Nasal swabs from patients and contacts were collected every 2 months. The SCORAD system assessed the severity of the AD. S. aureus isolates were evaluated to determine the methicillin resistance and the clonal lineages. RESULTS: Among 117 AD patients, 97 (82.9%) were already colonized with S. aureus and 26 (22.2%) had MRSA at the first evaluation. The incidence of MRSA acquisition in the cohort study was 27.47% (n = 25). The SCORAD assessments were: mild (46.15%), moderate (37.36%) or severe (16.48%). Risk factors were: colonized MRSA contacts (HR = 2.27; 95% CI: 1.16-7.54), use of cyclosporine (HR = 5.84; 95% CI: 1.70-19.98), moderate or severe AD (HR = 3.26; 95% CI: 1.13-9.37). Protective factors were: availability of running water (HR = 0.21; 95% CI: 0.049-0.96) and use of antihistamines (HR = 0.21; 95% IC: 0.64-0.75). MRSA isolates carried the SCCmec type IV and most of them were typed as USA800/ST5. CONCLUSIONS: The high incidence of MRSA acquisition found among AD patients and the risk factors associated show that an effective surveillance of MRSA colonization in these patients is needed

    Development and validation of PCR-based assays for diagnosis of American cutaneous leishmaniasis and identificatio nof the parasite species

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    In this study, PCR assays targeting different Leishmania heat-shock protein 70 gene (hsp70) regions, producing fragments ranging in size from 230-390 bp were developed and evaluated to determine their potential as a tool for the specific molecular diagnosis of cutaneous leishmaniasis (CL). A total of 70 Leishmania strains were analysed, including seven reference strains (RS) and 63 previously typed strains. Analysis of the RS indicated a specific region of 234 bp in the hsp70 gene as a valid target that was highly sensitive for detection of Leishmania species DNA with capacity of distinguishing all analyzed species, after polymerase chain reaction-restriction fragment length polymorfism (PCR-RFLP). This PCR assay was compared with other PCR targets used for the molecular diagnosis of leishmaniasis: hsp70 (1400-bp region), internal transcribed spacer (ITS)1 and glucose-6-phosphate dehydrogenase (G6pd). A good agreement among the methods was observed concerning the Leishmania species identification. Moreover, to evaluate the potential for molecular diagnosis, we compared the PCR targets hsp70-234 bp, ITS1, G6pd and mkDNA using a panel of 99 DNA samples from tissue fragments collected from patients with confirmed CL. Both PCR-hsp70-234 bp and PCR-ITS1 detected Leishmania DNA in more than 70% of the samples. However, using hsp70-234 bp PCR-RFLP, identification of all of the Leishmania species associated with CL in Brazil can be achieved employing a simpler and cheaper electrophoresis protocol

    Heme-Induced ROS in Trypanosoma Cruzi Activates CaMKII-Like That Triggers Epimastigote Proliferation. One Helpful Effect of ROS

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    Heme is a ubiquitous molecule that has a number of physiological roles. The toxic effects of this molecule have been demonstrated in various models, based on both its pro-oxidant nature and through a detergent mechanism. It is estimated that about 10 mM of heme is released during blood digestion in the blood-sucking bug's midgut. The parasite Trypanosoma cruzi, the agent of Chagas' disease, proliferates in the midgut of the insect vector; however, heme metabolism in trypanosomatids remains to be elucidated. Here we provide a mechanistic explanation for the proliferative effects of heme on trypanosomatids. Heme, but not other porphyrins, induced T. cruzi proliferation, and this phenomenon was accompanied by a marked increase in reactive oxygen species (ROS) formation in epimastigotes when monitored by ROS-sensitive fluorescent probes. Heme-induced ROS production was time-and concentration-dependent. In addition, lipid peroxidation and the formation of 4-hydroxy-2-nonenal (4-HNE) adducts with parasite proteins were increased in epimastigotes in the presence of heme. Conversely, the antioxidants urate and GSH reversed the heme-induced ROS. Urate also decreased parasite proliferation. Among several protein kinase inhibitors tested only specific inhibitors of CaMKII, KN93 and Myr-AIP, were able to abolish heme-induced ROS formation in epimastigotes leading to parasite growth impairment. Taken together, these data provide new insight into T. cruzi- insect vector interactions: heme, a molecule from the blood digestion, triggers epimastigote proliferation through a redox-sensitive signalling mechanism

    Guidelines for the management and treatment of periodic fever syndromes Cryopyrin-associated periodic syndromes (cryopyrinopathies – CAPS)

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    AbstractObjectiveTo establish guidelines based on cientific evidences for the management of cryopyrin associated periodic syndromes.Description of the evidence collection methodThe Guideline was prepared from 4 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation.Results1215 articles were retrieved and evaluated by title and abstract; from these, 42 articles were selected to support the recommendations.Recommendations1. The diagnosis of CAPS is based on clinical history and clinical manifestations, and later confirmed by genetic study. CAPS may manifest itself in three phenotypes: FCAS (mild form), MWS (intermediate form) and CINCA (severe form). Neurological, ophthalmic, otorhinolaryngological and radiological assessments may be highly valuable in distinguishing between syndromes; 2. The genetic diagnosis with NLRP3 gene analysis must be conducted in suspected cases of CAPS, i.e., individuals presenting before 20 years of age, recurrent episodes of inflammation expressed by a mild fever and urticaria; 3. Laboratory abnormalities include leukocytosis and elevated serum levels of inflammatory proteins; and 4. Targeted therapies directed against interleukin-1 lead to rapid remission of symptoms in most patients. However, there are important limitations on the long-term safety. None of the three anti-IL-1β inhibitors prevents progression of bone lesions

    The heme uptake process in Trypanosoma cruzi epimastigotes is inhibited by heme analogues and by inhibitors of ABC transporters

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    Heme (iron protoporphyrin IX) is an important molecule involved in many biological reactions, including oxygen transport, respiration, photosynthesis and drug detoxification. Trypanosoma cruzi parasites, the etiological agent of Chagas’ disease, take up heme from the environment to supply their nutritional needs because they do not synthesize this cofactor. However, the mechanisms involved in heme transport across biological membranes are poorly understood. Indeed, in T. cruzi, no heme transporter has yet been characterized. In the present work, we evaluate the heme uptake processes by T. cruzi epimastigotes using fluorescent heme-analogues. Heme uptake decreased significantly when cells were pretreated with different concentrations of SnPPIX, PdMPIX or ZnMPIX, this observed competition suggests that they are taken up by the same transport system. We studied the growth behavior of epimastigotes using the same heme-analogues and the treatments with SnPPIX or PdMPIX impaired cell growth but when heme was added to the culture medium the observed inhibition was partially reversed. In addition, we tested how the heme uptake processes are affected by the presence of different transporter inhibitors. When the cells were treated with inhibitors and then incubated with heme, heme uptake decreased significantly for all treatments. These results constitute a strong indication for the existence of a protein associated with porphyrin transport in T. cruzi, possibly ATP-binding cassette transporters (ABC-transporter).Fil: Cupello Peixoto, Mauricio. Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes (IBRAG). Departamento de Bioquímica. Laboratório de Interação Tripanossomatídeos e Vetores; Brazil.Fil: Fernandes de Souza, Cíntia. Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes (IBRAG). Departamento de Bioquímica. Laboratório de Interação Tripanossomatídeos e Vetores; Brazil.Fil: Buchensky, Celeste. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Biológica. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.Fil: Rocha Corrêa Soares, Juliana Baptista. Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Programa de Biologia Molecular e Biotecnologia. Laboratório de Bioquímica Redox; BrazilFil: Travassos Laranja, Gustavo Augusto. Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes (IBRAG). Departamento de Bioquímica. Laboratório de Interação Tripanossomatídeos e Vetores; Brazil.Fil: Garcia Pinto Coelho, Marsen. Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes (IBRAG). Departamento de Bioquímica. Laboratório de Interação Tripanossomatídeos e Vetores; Brazil.Fil: Cricco, Julia Alejandra. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Biológica. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.Fil: Paes, Marcia Cristina. Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes (IBRAG). Departamento de Bioquímica. Laboratório de Interação Tripanossomatídeos e Vetores; Brazil.Fil: Paes, Marcia Cristina. Instituto Nacional de Ciência e Tecnologia. Entomologia Molecular (INCT-EM); Brazi

    Stromal myofibroblasts in potentially malignant and malignant lesions of the oral cavity

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    CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORPrevious studies have demonstrated that myofibroblasts in the adjacent stroma are involved in the development and progression of malignant tumors. The aim of this study was to investigate the involvement of myofibroblasts in the progression of oral squamous cell carcinomas (OSCCs) by determining myofibroblast density in potentially malignant and malignant oral lesions. A total of 69 potentially malignant oral lesions (leukoplakias with mild, moderate or severe dysplasia), 90 OSCCs (well-, moderately and poorly differentiated), eight oral verrucous carcinomas and 29 fibrous hyperplasias were examined for the presence of myofibroblasts using immunohistochemical detection of isoform a of smooth muscle actin. Myofibroblasts were not identified in the adjacent stroma of fibrous hyperplasias and potentially malignant oral lesions, whereas 59.8% of the oral carcinomas exhibited myofibroblasts in various densities. The density was significantly higher in moderately and poorly differentiated OSCCs when compared with well-differentiated tumors (P=0.04 and P=0.007, respectively). In vernicous carcinomas, the specific variant of well-differentiated OSCC, stromal myofibroblasts were not detected. The results of the present study demonstrated that immunodetection of myofibroblasts does not aid with the determination of the malignant transformation potential of oral dysplasias, although moderately and poorly differentiated tumors exhibited a significantly higher density of myofibroblasts. The results reinforce the hypothesis that myofibroblasts may contribute to oral tumorigenesis, indicating that verification and monitoring of such may serve as a putative marker of OSCC behavior.Previous studies have demonstrated that myofibroblasts in the adjacent stroma are involved in the development and progression of malignant tumors. The aim of this study was to investigate the involvement of myofibroblasts in the progression of oral squamous cell carcinomas (OSCCs) by determining myofibroblast density in potentially malignant and malignant oral lesions. A total of 69 potentially malignant oral lesions (leukoplakias with mild, moderate or severe dysplasia), 90 OSCCs (well-, moderately and poorly differentiated), eight oral verrucous carcinomas and 29 fibrous hyperplasias were examined for the presence of myofibroblasts using immunohistochemical detection of isoform a of smooth muscle actin. Myofibroblasts were not identified in the adjacent stroma of fibrous hyperplasias and potentially malignant oral lesions, whereas 59.8% of the oral carcinomas exhibited myofibroblasts in various densities. The density was significantly higher in moderately and poorly differentiated OSCCs when compared with well-differentiated tumors (P=0.04 and P=0.007, respectively). In vernicous carcinomas, the specific variant of well-differentiated OSCC, stromal myofibroblasts were not detected. The results of the present study demonstrated that immunodetection of myofibroblasts does not aid with the determination of the malignant transformation potential of oral dysplasias, although moderately and poorly differentiated tumors exhibited a significantly higher density of myofibroblasts. The results reinforce the hypothesis that myofibroblasts may contribute to oral tumorigenesis, indicating that verification and monitoring of such may serve as a putative marker of OSCC behaviorSpandidos Publications92667670CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORsem informaçãosem informaçãosem informaçãoGréciaOncology lettersOncol lettAthen

    Activin a immunoexpression as predictor of occult lymph node metastasis and overall survival in oral tongue squamous cell carcinoma

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    FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOBackgroundThe presence of regional lymph node metastasis has an important impact on clinical management and prognostication of patients with oral tongue squamous cell carcinoma (SCC). Approximately 30% to 50% of patients with oral tongue SCC have regional metastasis at diagnosis, but the limited sensibility of the current diagnostic methods used for neck staging does not allow detection of all cases, leaving a significant number of undiagnosed metastasis (occult lymph node metastasis). In this study, we evaluated whether clinicopathologic features and immunohistochemical detection of carcinoma-associated fibroblasts (CAFs) and activin A could be predictive markers for occult lymph node metastasis in oral tongue SCC. MethodsOne hundred ten patients with primary oral tongue SCC, who were classified with early stage tumor (stage I and II) and received surgical treatment with elective neck dissection, were enrolled in the study. ResultsAmong all examined features, only high immunohistochemical expression of activin A was significantly associated with presence of occult lymph node metastasis (p=.006). Multivariate survival analysis using the Cox proportional hazard model showed that the expression of activin A was an independent marker of reduced overall survival with a 5-year survival of 89.7% for patients with low expression compared to 76.5% for those with high expression (hazard ratio [HR], 2.44; 95% confidence interval [CI], 1.55-3.85; p=.012). ConclusionOur results demonstrated that immunodetection of activin A can be useful for prognostication of oral tongue SCC, revealing patients with occult lymph node metastasis and lower overall survival. (c) 2014 Wiley Periodicals, Inc. Head Neck37: 479-486, 2015The presence of regional lymph node metastasis has an important impact on clinical management and prognostication of patients with oral tongue squamous cell carcinoma (SCC). Approximately 30% to 50% of patients with oral tongue SCC have regional metastasis at diagnosis, but the limited sensibility of the current diagnostic methods used for neck staging does not allow detection of all cases, leaving a significant number of undiagnosed metastasis (occult lymph node metastasis). In this study, we evaluated whether clinicopathologic features and immunohistochemical detection of carcinoma-associated fibroblasts (CAFs) and activin A could be predictive markers for occult lymph node metastasis in oral tongue SCC. One hundred ten patients with primary oral tongue SCC, who were classified with early stage tumor (stage I and II) and received surgical treatment with elective neck dissection, were enrolled in the study. ResultsAmong all examined features, only high immunohistochemical expression of activin A was significantly associated with presence of occult lymph node metastasis (p=.006). Multivariate survival analysis using the Cox proportional hazard model showed that the expression of activin A was an independent marker of reduced overall survival with a 5-year survival of 89.7% for patients with low expression compared to 76.5% for those with high expression (hazard ratio [HR], 2.44; 95% confidence interval [CI], 1.55-3.85; p=.012). Our results demonstrated that immunodetection of activin A can be useful for prognostication of oral tongue SCC, revealing patients with occult lymph node metastasis and lower overall survivalJohn Wiley & Sons374479486FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP [2011/00691-7, 2011/03507-3]CNPq [302464/2011-5]2011/00691‐7; 2011/03507‐3302464/2011‐5New York, N

    Mutagenic and Cytotoxicity LQB 123 Profile: Safety and Tripanocidal Effect of a Phenyl-t-Butylnitrone Derivative

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    Submitted by Sandra Infurna ([email protected]) on 2018-02-27T13:29:45Z No. of bitstreams: 1 rubem_mennabarreto_etal_IOC_2017.pdf: 1911190 bytes, checksum: 4c162cf9427198496253166cb5741a47 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2018-02-27T13:51:49Z (GMT) No. of bitstreams: 1 rubem_mennabarreto_etal_IOC_2017.pdf: 1911190 bytes, checksum: 4c162cf9427198496253166cb5741a47 (MD5)Made available in DSpace on 2018-02-27T13:51:49Z (GMT). No. of bitstreams: 1 rubem_mennabarreto_etal_IOC_2017.pdf: 1911190 bytes, checksum: 4c162cf9427198496253166cb5741a47 (MD5) Previous issue date: 2017Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes. Departamento de Bioquímica. Laboratório de Interação Tripanossomatídeos e Vetores. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Rio de Janeiro. Unidade de Desenvolvimento Tecnológico de Triagem de Compostos Químicos para Doenças Negligenciadas com Ênfase Farmacológica contra a Doença de Chagas. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes. Departamento de Bioquímica. Laboratório de Interação Tripanossomatídeos e Vetores. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Rio de Janeiro. Unidade de Desenvolvimento Tecnológico de Triagem de Compostos Químicos para Doenças Negligenciadas com Ênfase Farmacológica contra a Doença de Chagas. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes. Departamento de Bioquímica. Laboratório de Interação Tripanossomatídeos e Vetores. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes. Departamento de Biofísica e Biometria. Laboratório de Mutagênese Ambiental. Rio de janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil.Universidade do Estado do Rio de Janeiro. Departamento de Química Orgânica. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes. Departamento de Bioquímica. Laboratório de Interação Tripanossomatídeos e Vetores. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Rio de Janeiro. Unidade de Desenvolvimento Tecnológico de Triagem de Compostos Químicos para Doenças Negligenciadas com Ênfase Farmacológica contra a Doença de Chagas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Laboratório de Química Bioorgânica. Rio de Janeiro, RJ, BrasilUniversidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes. Departamento de Bioquímica. Laboratório de Interação Tripanossomatídeos e Vetores. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Rio de Janeiro. Unidade de Desenvolvimento Tecnológico de Triagem de Compostos Químicos para Doenças Negligenciadas com Ênfase Farmacológica contra a Doença de Chagas. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes. Departamento de Biofísica e Biometria. Laboratório de Mutagênese Ambiental. Rio de janeiro, RJ, BrasilUniversidade do Estado do Rio de Janeiro. Departamento de Química Orgânica. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes. Departamento de Bioquímica. Laboratório de Interação Tripanossomatídeos e Vetores. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Rio de Janeiro. Unidade de Desenvolvimento Tecnológico de Triagem de Compostos Químicos para Doenças Negligenciadas com Ênfase Farmacológica contra a Doença de Chagas. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia, Entomologia Molecular. Rio de Janeiro, RJ, Brasil.The therapeutic options for Chagas disease are limited and its treatment presents a number of drawbacks including toxicity, drug resistance, and insufficient effectiveness against the chronic stage of the disease. Therefore, new therapeutical options are mandatory. In the present work, we evaluated the effect of a phenyl-tert-butylnitrone (PBN) derivate, LQB 123, againstTrypanosoma cruziforms. LQB 123 presented a trypanocidal effect against bloodstream trypomastigotes (IC50= 259.4 ± 6.1 μM) and intracellular amastigotes infecting peritoneal macrophages (IC50= 188.2 ± 47.5 μM), with no harmful effects upon the mammalian cells (CC50values greater than 4 mM), resulting in a high selectivity index (CC50/IC50> 20). Additionally, metacyclic trypomastigotes submitted to LQB 123 presented an IC50of about 191.8 ± 10.5 μM and epimastigotes forms incubated with different concentrations of LQB 123 presented an inhibition of parasite growth with an IC50of 255.1 ± 3.6 μM. Finally, we investigated the mutagenic potential of the nitrone by theSalmonella/microsome assay and observed no induction of mutagenicity even in concentrations as high as 33000 μM. Taken together, these results present a nonmutagenic compound, with trypanocidal activity against all relevant forms ofT. cruzi, offering new insights into CD treatment suggesting additional in vivo tests
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