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1.
Curr Res Microb Sci ; 3: 100110, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35199071

RESUMO

Chagas disease (CD), caused by Trypanosoma cruzi, occurs in several countries in Latin America and non-endemic countries. Heterogeneity among T. cruzi population has been the Achilles' heel to find a better treatment for CD. In this study, we characterized the biochemical parameters and mitochondrial bioenergetics of epimastigotes differentiated from eight T. cruzi isolates (I1-I8) obtained from Brazilian CD patients. Molecular analysis of parasites DTUs grouped all of them as TcII. The profile of the growth curves in axenic cultures was distinct among them, except for I1 and I3 and I2 and I4. Doubling times, growth rates, cell body length, and resistance to benznidazole were also significantly different among them. All the isolates were more glucose-dependent than other T. cruzi strains adapted to grow in axenic culture. Mitochondrial bioenergetics analysis showed that each isolate behaved differently regarding oxygen consumption rates in non-permeabilized and in digitonin-permeabilized cells in the presence of a complex II-linked substrate. When complex IV-linked respiratory chain substrate was used to provide electrons to the mitochondrial respiratory chain (MRC), similarity among the isolates was higher. Our findings show that TcII epimastigotes derived from patients' trypomastigotes displayed their own characteristics in vitro, highlighting the intra-TcII diversity, especially regarding the functionality of mitochondrial respiratory complexes II and IV. Understanding T. cruzi intraspecific biological features help us to move a step further on our comprehension regarding parasite's survival and adaptability offering clues to improve the development of new therapies for CD.

2.
Acta Trop ; 222: 106054, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34273309

RESUMO

This study aimed to identify the Trypanosoma cruzi genotypes and their relationship with parasitic load in distinct geographic and ecotypic populations of Triatoma brasiliensis in two sites, including one where a Chagas disease (ChD) outbreak occurred in Rio Grande do Norte state, Brazil. Triatomine captures were performed in peridomestic and sylvatic ecotopes in two municipalities: Marcelino Vieira - affected by the outbreak; and Currais Novos - where high pressure of peridomestic triatomine infestation after insecticide spraying have been reported. The kDNA-PCR was used to select 124 T. cruzi positive triatomine samples, of which 117 were successfully genotyped by fluorescent fragment length barcoding (FFLB). Moreover, the T. cruzi load quantification was performed using a multiplex TaqMan qPCR. Our findings showed a clear ecotypic segregation between TcI and TcII harboured by T. brasiliensis (p<0.001). Although no genotypes were ecotypically exclusive, TcI was predominant in peridomestic ecotopes (86%). In general, T. brasiliensis from Rio Grande do Norte had a higher T. cruzi load varying from 3.94 to 7.66 x 106T. cruzi per insect. Additionally, TcII (median value=299,504 T. cruzi/intestine unit equivalents) had more than twice (p=0.1) the parasite load of TcI (median value=149,077 T. cruzi/intestine unit equivalents), which can be attributed to a more ancient co-evolution with T. brasiliensis. The higher prevalence of TcII in the sylvatic T. brasiliensis (70%) could be associated with a more diversified source of bloodmeals for wild insect populations. Either TcI or TcII may have been responsible for the ChD outbreak that occurred in the city of Marcelino Vieira. On the other hand, a smaller portion of T. brasiliensis was infected by TcIII (3%) in the peridomicile, in addition to T. rangeli genotype A (1%), often found in mixed infections. Our results highlight the need of understanding the patterns of T. cruzi genotype´s development and circulation in insect vectors and reservoirs as a mode of tracking situations of epidemiologic importance, as the ChD outbreak recently recorded for Northeastern Brazil.


Assuntos
Doença de Chagas , Triatoma , Trypanosoma cruzi , Animais , Brasil/epidemiologia , Doença de Chagas/epidemiologia , Surtos de Doenças , Genótipo , Humanos , Carga Parasitária , Reação em Cadeia da Polimerase em Tempo Real , Triatoma/parasitologia , Trypanosoma cruzi/genética
3.
Planta Med ; 86(11): 782-789, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32512613

RESUMO

Ten lignans (1:  - 10: ) were isolated from the hexane-ethyl acetate extract of Phyllanthus amarus leaves. Three of them, cubebin dimethyl ether (3: ), urinatetralin (4: ), and lintetralin (7: ) are described for the first time in this species, while phyllanthin (1: ), niranthin (2: ), 5-demethoxyniranthin (5: ), isolintetralin (6: ), hypophyllanthin (8: ), nirtetralin (9: ), and phyltetralin (10: ) have been already reported from P. amarus. Among the lignans tested against Trypanosoma cruzi intracellular amastigotes, 2: was the most active with an EC50 of 35.28 µM. Lignans 2, 5, 7: , and 9: showed inhibitory effects against Leishmania amazonensis promastigotes with EC50 of 56.34, 51.86, 23.57, and 43.27 µM, respectively. During in vitro infection assays, 5: reduced amastigotes by 91% at 103.68 µM concentration, whereas 7: and 9: reduced amastigotes by approximately 84% at 47.5 and 86.04 µM, respectively. Lignans 5, 7: , and 9: were more potent in intracellular amastigotes with EC50 of 2.76, 8.30, and 15.83 µM, respectively, than in promastigotes. CC50 for all samples was > 100 µg/mL, thus revealing low cytotoxicity against macrophages, and selectivity against the parasite. L. amazonensis promastigotes treated with compounds 2: and 9: showed decreased respiratory control of 38% and 25%, respectively, suggesting a change in mitochondrial membrane potential and lower ATP production.


Assuntos
Antiprotozoários , Leishmania mexicana , Lignanas , Phyllanthus , Extratos Vegetais
4.
Rev Soc Bras Med Trop ; 51(6): 831-835, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30517539

RESUMO

INTRODUCTION: Chagas disease (CD) prevention and control rely on studies of its distribution, characteristics of individuals affected and mode of transmission. CD data in Brazil are scarce; a retrospective analysis of the clinical characteristics of 80 patients treated at the Clinical Hospital of UNICAMP, Campinas, Brazil, was performed. METHODS: Patient data records were analyzed. RESULTS: Thirty percent of the patients probably got infected through vector-borne transmission, 65% came from endemic areas, a predominance of cardiac and cardiodigestive forms was found among males, and the cardiac form prevailed (51%). CONCLUSIONS: The results update the view on the epidemiology of CD in Campinas, Brazil.


Assuntos
Doença de Chagas , Registros Hospitalares/estatística & dados numéricos , Brasil/epidemiologia , Doença de Chagas/diagnóstico , Doença de Chagas/tratamento farmacológico , Doença de Chagas/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos
5.
Rev. Soc. Bras. Med. Trop ; 51(6): 831-835, Nov.-Dec. 2018. graf
Artigo em Inglês | LILACS | ID: biblio-1041490

RESUMO

Abstract INTRODUCTION: Chagas disease (CD) prevention and control rely on studies of its distribution, characteristics of individuals affected and mode of transmission. CD data in Brazil are scarce; a retrospective analysis of the clinical characteristics of 80 patients treated at the Clinical Hospital of UNICAMP, Campinas, Brazil, was performed. METHODS: Patient data records were analyzed. RESULTS: Thirty percent of the patients probably got infected through vector-borne transmission, 65% came from endemic areas, a predominance of cardiac and cardiodigestive forms was found among males, and the cardiac form prevailed (51%). CONCLUSIONS: The results update the view on the epidemiology of CD in Campinas, Brazil.


Assuntos
Humanos , Masculino , Feminino , Registros Hospitalares/estatística & dados numéricos , Doença de Chagas/diagnóstico , Doença de Chagas/tratamento farmacológico , Doença de Chagas/epidemiologia , Brasil/epidemiologia , Prevalência , Estudos Retrospectivos , Pessoa de Meia-Idade
6.
PLoS Negl Trop Dis ; 11(8): e0005852, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28832582

RESUMO

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, presents a variable clinical course, varying from asymptomatic to serious debilitating pathologies with cardiac, digestive or cardio-digestive impairment. Previous studies using two clonal T. cruzi populations, Col1.7G2 (T. cruzi I) and JG (T. cruzi II) demonstrated that there was a differential tissue distribution of these parasites during infection in BALB/c mice, with predominance of JG in the heart. To date little is known about the mechanisms that determine this tissue selection. Upon infection, host cells respond producing several factors, such as reactive oxygen species (ROS), cytokines, among others. Herein and in agreement with previous data from the literature we show that JG presents a higher intracellular multiplication rate when compared to Col1.7G2. We also showed that upon infection cardiomyocytes in culture may increase the production of oxidative species and its levels are higher in cultures infected with JG, which expresses lower levels of antioxidant enzymes. Interestingly, inhibition of oxidative stress severely interferes with the intracellular multiplication rate of JG. Additionally, upon H2O2-treatment increase in intracellular Ca2+ and oxidants were observed only in JG epimastigotes. Data presented herein suggests that JG and Col1.7G2 may sense extracellular oxidants in a distinct manner, which would then interfere differently with their intracellular development in cardiomyocytes.


Assuntos
Interações Hospedeiro-Parasita , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/parasitologia , Oxidantes/metabolismo , Trypanosoma cruzi/crescimento & desenvolvimento , Animais , Antioxidantes/farmacologia , Cálcio/metabolismo , Respiração Celular , Células Cultivadas , Cardiomiopatia Chagásica/parasitologia , Doença de Chagas/parasitologia , Citocinas/biossíntese , Citocinas/imunologia , Humanos , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Miócitos Cardíacos/efeitos dos fármacos , Oxidantes/farmacologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismo , Trypanosoma cruzi/classificação , Trypanosoma cruzi/fisiologia
7.
Parasitology ; 144(11): 1498-1510, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28653592

RESUMO

Trypanosoma cruzi is exposed to oxidative stresses during its life cycle, and amongst the strategies employed by this parasite to deal with these situations sits a peculiar trypanothione-dependent antioxidant system. Remarkably, T. cruzi's antioxidant repertoire does not include catalase. In an attempt to shed light on what are the reasons by which this parasite lacks this enzyme, a T. cruzi cell line stably expressing catalase showed an increased resistance to hydrogen peroxide (H2O2) when compared with wild-type cells. Interestingly, preconditioning carried out with low concentrations of H2O2 led untransfected parasites to be as much resistant to this oxidant as cells expressing catalase, but did not induce the same level of increased resistance in the latter ones. Also, presence of catalase decreased trypanothione reductase and increased superoxide dismutase levels in T. cruzi, resulting in higher levels of residual H2O2 after challenge with this oxidant. Although expression of catalase contributed to elevated proliferation rates of T. cruzi in Rhodnius prolixus, it failed to induce a significant increase of parasite virulence in mice. Altogether, these results indicate that the absence of a gene encoding catalase in T. cruzi has played an important role in allowing this parasite to develop a shrill capacity to sense and overcome oxidative stress.


Assuntos
Catalase/metabolismo , Estresse Oxidativo , Transdução de Sinais , Trypanosoma cruzi/metabolismo , Animais , Catalase/genética , Linhagem Celular , Doença de Chagas/parasitologia , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Camundongos , NADH NADPH Oxirredutases/metabolismo , Rhodnius/parasitologia , Superóxido Dismutase/metabolismo , Transfecção , Trypanosoma cruzi/efeitos dos fármacos , Trypanosoma cruzi/patogenicidade
8.
Mem. Inst. Oswaldo Cruz ; 111(7): 460-468, tab, graf
Artigo em Inglês | LILACS | ID: lil-787557

RESUMO

The 70 kDa heat shock protein (HSP70) is a molecular chaperone that assists the parasite Leishmania in returning to homeostasis after being subjected to different types of stress during its life cycle. In the present study, we evaluated the effects of HSP70 transfection of L. amazonensis promastigotes (pTEX-HSP70) in terms of morphology, resistance, infectivity and mitochondrial bioenergetics. The pTEX-HSP70 promastigotes showed no ultrastructural morphological changes compared to control parasites. Interestingly, the pTEX-HSP70 promastigotes are resistant to heat shock, H2O2-induced oxidative stress and hyperbaric environments. Regarding the bioenergetics parameters, the pTEX-HSP70 parasites had higher respiratory rates and released less H2O2 than the control parasites. Nevertheless, the infectivity capacity of the parasites did not change, as verified by the infection of murine peritoneal macrophages and human macrophages, as well as the infection of BALB/c mice. Together, these results indicate that the overexpression of HSP70 protects L. amazonensis from stress, but does not interfere with its infective capacity.


Assuntos
Animais , Feminino , Proteínas de Choque Térmico HSP70/fisiologia , Leishmania mexicana/fisiologia , Leishmaniose Cutânea/parasitologia , Proteínas de Protozoários/fisiologia , Estresse Fisiológico , Proteínas de Choque Térmico HSP70/genética , Leishmania mexicana/genética , Leishmania mexicana/ultraestrutura , Macrófagos/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/fisiologia , Estresse Oxidativo , Proteínas de Protozoários/genética , Transfecção/métodos
9.
Mem Inst Oswaldo Cruz ; 0: 0, 2016 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-27304024

RESUMO

The 70 kDa heat shock protein (HSP70) is a molecular chaperone that assists the parasite Leishmania in returning to homeostasis after being subjected to different types of stress during its life cycle. In the present study, we evaluated the effects of HSP70 transfection of L. amazonensis promastigotes (pTEX-HSP70) in terms of morphology, resistance, infectivity and mitochondrial bioenergetics. The pTEX-HSP70 promastigotes showed no ultrastructural morphological changes compared to control parasites. Interestingly, the pTEX-HSP70 promastigotes are resistant to heat shock, H2O2-induced oxidative stress and hyperbaric environments. Regarding the bioenergetics parameters, the pTEX-HSP70 parasites had higher respiratory rates and released less H2O2 than the control parasites. Nevertheless, the infectivity capacity of the parasites did not change, as verified by the infection of murine peritoneal macrophages and human macrophages, as well as the infection of BALB/c mice. Together, these results indicate that the overexpression of HSP70 protects L. amazonensis from stress, but does not interfere with its infective capacity.


Assuntos
Proteínas de Choque Térmico HSP70/fisiologia , Leishmania mexicana/fisiologia , Leishmaniose Cutânea/parasitologia , Proteínas de Protozoários/fisiologia , Estresse Fisiológico , Animais , Feminino , Proteínas de Choque Térmico HSP70/genética , Leishmania mexicana/genética , Leishmania mexicana/ultraestrutura , Macrófagos/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/fisiologia , Estresse Oxidativo , Proteínas de Protozoários/genética , Transfecção/métodos
10.
Mutat Res Rev Mutat Res ; 767: 8-22, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27036062

RESUMO

Trypanosoma cruzi, the causative agent of Chagas disease, is an obligatory intracellular parasite with a digenetic life cycle. Due to the variety of host environments, it faces several sources of oxidative stress. In addition to reactive oxygen species (ROS) produced by its own metabolism, T. cruzi must deal with high ROS levels generated as part of the host's immune responses. Hence, the conclusion that T. cruzi has limited ability to deal with ROS (based on the lack of a few enzymes involved with oxidative stress responses) seems somewhat paradoxical. Actually, to withstand such variable sources of oxidative stress, T. cruzi has developed complex defence mechanisms. This includes ROS detoxification pathways that are distinct from the ones in the mammalian host, DNA repair pathways and specialized polymerases, which not only protect its genome from the resulting oxidative damage but also contribute to the generation of genetic diversity within the parasite population. Recent studies on T. cruzi's DNA repair pathways as mismatch repair (MMR) and GO system suggested that, besides a role associated with DNA repair, some proteins of these pathways may also be involved in signalling oxidative damage. Recent data also suggested that an oxidative environment might be beneficial for parasite survival within the host cell as it contributes to iron mobilization from the host's intracellular storages. Besides contributing to the understanding of basic aspects of T. cruzi biology, these studies are highly relevant since oxidative stress pathways are part of the poorly understood mechanisms behind the mode of action of drugs currently used against this parasite. By unveiling new peculiar aspects of T. cruzi biology, emerging data on DNA repair pathways and other antioxidant defences from this parasite have revealed potential new targets for a much needed boost in drug development efforts towards a better treatment for Chagas disease.


Assuntos
Antioxidantes/metabolismo , Dano ao DNA/genética , Reparo de Erro de Pareamento de DNA/genética , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Trypanosoma cruzi/metabolismo , Doença de Chagas/parasitologia , Doença de Chagas/terapia , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Oxirredução , Trypanosoma cruzi/genética , Trypanosoma cruzi/imunologia
11.
Nat Prod Res ; 27(11): 997-1001, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22583044

RESUMO

The essential oils from the leaves of Annona pickelii and Annona salzmannii (Annonaceae) were obtained by hydrodistillation using a Clevenger apparatus, and analysed by GC-MS and GC-FID. A total of 21 compounds were identified in the essential oil of A. pickelii and 23 in that of A. salzmannii; sesquiterpenes predominated in both essential oils. Bicyclogermacrene (38.0%), (E)-caryophyllene (27.8%), α-copaene (6.9%) and α-humulene (4.0%) were the main components of A. pickelii, while δ-cadinene (22.6%), (E)-caryophyllene (21.4%), α-copaene (13.3%), bicyclogermacrene (11.3%) and germacrene D (6.9%) were the main components of A. salzmannii. The biological activities of the essential oils against Trypanosoma cruzi epimastigote forms and cytotoxicity against tumour cell lines (antitumour) were investigated. The essential oils showed potent trypanocidal and antitumour activities with values of IC50 lower than 100 µg mL(-1).


Assuntos
Annonaceae/química , Antineoplásicos Fitogênicos/farmacologia , Óleos Voláteis/química , Tripanossomicidas/farmacologia , Linhagem Celular , Cromatografia Gasosa , Humanos , Concentração Inibidora 50 , Espectrometria de Massas , Óleos Voláteis/farmacologia
12.
Nat Prod Commun ; 7(2): 265-6, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22474976

RESUMO

The essential oil from the leaves of Annona vepretorun was obtained by hydrodistillation using a Clevenger-type apparatus and analyzed by GC-MS and GC-FID. Eighteen compounds representing 98.1% of the crude essential oil were identified. The major compounds identified were bicyclogermacrene (43.7%), spathulenol (11.4%), alpha-felandrene (10.0%), alpha-pinene (7.1%), (E)-beta-ocimene (6.8%), germacrene D (5.8%), and p-cymene (4.2%). The trypanocidal activity against Trypanosoma cruzi epimastigote forms, as well as, the antimicrobial and antioxidant proprieties was investigated. The essential oil showed a potent trypanocidal activity with IC50 value of 31.9 +/-1.3 microg x mL(-1). For antimicrobial activity, the best result was observed against Candida tropicalis with a MIC value of 100 microg x mL(-1). For antioxidant capacity the essential oil showed weak activity.


Assuntos
Annona/química , Anti-Infecciosos/farmacologia , Óleos Voláteis/farmacologia , Folhas de Planta/química , Óleos Vegetais/farmacologia , Anti-Infecciosos/química , Óleos Voláteis/química , Óleos Vegetais/química
13.
J Bioenerg Biomembr ; 43(4): 419-24, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21732175

RESUMO

Trypanosoma cruzi cytosolic (TcCPx) and mitochondrial tryparedoxin peroxidase (TcMPx) play a fundamental role in H(2)O(2) detoxification. Herein, mitochondrial bioenergetics was evaluated in cells that overexpressed TcCPx (CPx) and TcMPx (MPx) and in pTEX. In MPx, a higher expression was observed for TcCPx, and the same correlation was true for CPx. Differences in H(2)O(2) release among the overexpressing cells were detected when the mitochondrial respiratory chain was inhibited using antimycin A or thenoyltrifluoroacetone. MPx had higher O(2) consumption rates than pTEX and CPx, especially in the presence of oligomycin. In all of the cells, the mitochondrial membrane potential and the ATP levels were similar. Because of the mild uncoupling that was observed in MPx, the presence or induction of a proton transporter in the mitochondrial membrane is suggested when TcMPx is expressed at higher levels. Our results show a possible interplay between the cytosolic and mitochondrial antioxidant systems in a trypanosomatid.


Assuntos
Mitocôndrias/enzimologia , Peroxirredoxinas/metabolismo , Trypanosoma cruzi/enzimologia , Animais , Células Cultivadas , Citosol/enzimologia , Metabolismo Energético , Potencial da Membrana Mitocondrial/fisiologia
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