RESUMO
Distinct populations of Trypanosoma cruzi interact with mammalian cardiac muscle cells causing different inflammation patterns and low heart functionality. During T. cruzi infection, the extracellular ATP is hydrolyzed to tri- and/or diphosphate nucleotides, based on the infectivity, virulence, and regulation of the inflammatory response. T. cruzi carries out this hydrolysis through the T. cruzi ectonucleotidase, NTPDase-1 (TcNTPDase-1). This study aimed to evaluate the role of TcNTPDase-1 in culture rich in metacyclic trypomastigote forms (MT) and cell culture-derived trypomastigote forms (CT) from Colombiana (discrete typing unit - DTU I), VL-10 (DTU II), and CL (DTU VI) strains of T. cruzi. For this, we measured TcNTPDase-1 activity in suramin-treated and untreated parasites and infected J774 cells and C57BL/6 mice with suramin pre-treated parasites to assess parasitic and inflammatory cardiac profile in the acute phase of infection. Our data indicated a higher TcNTPDase-1 activity for ATP in culture rich in metacyclic trypomastigote forms from Colombiana strain in comparison to those from VL-10 and CL strains. The cell culture-derived trypomastigote forms from CL strain presented higher capacity to hydrolyze ATP than those from Colombiana and VL-10 strains. Suramin inhibited ATP hydrolysis in all studied parasite forms and strains. Suramin pre-treated parasites reduced J774 cell infection and increased nitrite production in vitro. In vivo studies showed a reduction of inflammatory infiltrate in the cardiac tissues of animals infected with cell culture-derived trypomastigote forms from suramin pre-treated Colombiana strain. In conclusion, TcNTPDase-1 activity in trypomastigotes forms drives part of the biological characteristics observed in distinct DTUs and may induce cardiac pathogenesis during T. cruzi infection.
Assuntos
Antígenos CD , Apirase , Doença de Chagas , Proteínas de Protozoários , Trypanosoma cruzi , Fatores de Virulência , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Apirase/genética , Apirase/metabolismo , Linhagem Celular Tumoral , Doença de Chagas/enzimologia , Doença de Chagas/genética , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Especificidade da Espécie , Trypanosoma cruzi/enzimologia , Trypanosoma cruzi/genética , Trypanosoma cruzi/patogenicidade , Fatores de Virulência/genética , Fatores de Virulência/metabolismoRESUMO
Objective Provide a comprehensive view of the events surrounding the sugar consumption, under conditions of energy equivalence; through the analysis of behavioral aspects of intake, and of biochemical, metabolic and physiological parameters, as well as the effect of this nutrient on the plasticity of adipose tissue. Materials and methods Newly weaned male Wistar rats were classified in two groups and subjected to the following normocaloric diets: standard chow diet or to high-sugar diet (HSD) ad libitum for 18 weeks. Results The animals submitted to the HSD were associated with a lower caloric intake during the 18 weeks of experimentation. However, the HSD induced a significant increase in body weight, white adipose tissue weight, adiposity index, Lee index, and the levels of triglycerides and very low-density lipoprotein in the serum. In addition, it induced glucose intolerance, insulin resistance and compensatory increase of insulin secretion by pancreatic ß-cells. Also increased heart rate and induced hyperplasia, and hypertrophy of retroperitoneal visceral adipose tissue. In the liver, the HSD was associated with increased hepatic lipid content (i.e., triglycerides and cholesterol) and hepatomegaly. Conclusion The post-weaning consumption of HSD induces an adaptive response in metabolism; however, such an event is not enough to reverse the homeostatic imbalance triggered by the chronic consumption of this macronutrient, leading to the development of metabolic syndrome, irrespective of caloric intake. These findings corroborate recent evidence indicating that sugar is a direct contributor to metabolic diseases independent of a positive energy balance. Arch Endocrinol Metab. 2020;64(1):71-81.
Assuntos
Tecido Adiposo/metabolismo , Açúcares da Dieta/metabolismo , Ingestão de Energia , Metabolismo Energético , Doenças Metabólicas/metabolismo , Obesidade/metabolismo , Animais , Açúcares da Dieta/efeitos adversos , Açúcares da Dieta/sangue , Masculino , Doenças Metabólicas/sangue , Obesidade/sangue , Obesidade/etiologia , Ratos , Ratos WistarRESUMO
ABSTRACT Objective Provide a comprehensive view of the events surrounding the sugar consumption, under conditions of energy equivalence; through the analysis of behavioral aspects of intake, and of biochemical, metabolic and physiological parameters, as well as the effect of this nutrient on the plasticity of adipose tissue. Materials and methods Newly weaned male Wistar rats were classified in two groups and subjected to the following normocaloric diets: standard chow diet or to high-sugar diet (HSD) ad libitum for 18 weeks. Results The animals submitted to the HSD were associated with a lower caloric intake during the 18 weeks of experimentation. However, the HSD induced a significant increase in body weight, white adipose tissue weight, adiposity index, Lee index, and the levels of triglycerides and very low-density lipoprotein in the serum. In addition, it induced glucose intolerance, insulin resistance and compensatory increase of insulin secretion by pancreatic β-cells. Also increased heart rate and induced hyperplasia, and hypertrophy of retroperitoneal visceral adipose tissue. In the liver, the HSD was associated with increased hepatic lipid content (i.e., triglycerides and cholesterol) and hepatomegaly. Conclusion The post-weaning consumption of HSD induces an adaptive response in metabolism; however, such an event is not enough to reverse the homeostatic imbalance triggered by the chronic consumption of this macronutrient, leading to the development of metabolic syndrome, irrespective of caloric intake. These findings corroborate recent evidence indicating that sugar is a direct contributor to metabolic diseases independent of a positive energy balance. Arch Endocrinol Metab. 2020;64(1):71-81
Assuntos
Animais , Masculino , Ratos , Ingestão de Energia , Tecido Adiposo/metabolismo , Metabolismo Energético , Açúcares da Dieta/metabolismo , Doenças Metabólicas/metabolismo , Obesidade/metabolismo , Ratos Wistar , Açúcares da Dieta/efeitos adversos , Açúcares da Dieta/sangue , Doenças Metabólicas/sangueRESUMO
INTRODUCTION: The biological diversity of Trypanosoma cruzi strains plays an important role in the clinical and epidemiological features of Chagas disease. METHODS: Eight T. cruzi strains isolated from children living in a Chagas disease vector-controlled area of Jequitinhonha Valley, State of Minas Gerais, Brazil, were genetically and biologically characterized. RESULTS: The characterizations demonstrated that all of the strains belonged to T. cruzi II, and showed high infectivity and a variable mean maximum peak of parasitemia. Six strains displayed low parasitemia, and two displayed moderate parasitemia. Later peaks of parasitemia and a predominance of intermediate and large trypomastigotes in all T. cruzi strains were observed. The mean pre-patent period was relatively short (4.2 ± 0.25 to 13.7 ± 3.08 days), whereas the patent period ranged from 3.3 ± 1.08 to 34.5 ± 3.52 days. Mortality was observed only in animals infected with strain 806 (62.5%). Histopathological analysis of the heart showed that strains 501 and 806 caused inflammation, but fibrosis was observed only in animals infected with strain 806. CONCLUSIONS: The results indicate the presence of an association between the biological behavior in mice and the genetic characteristics of the parasites. The study also confirmed general data from Brazil where T. cruzi II lineage is the most prevalent in the domiciliary cycle and generally has low virulence, with some strains capable of inducing inflammatory processes and fibrosis.
Assuntos
Doença de Chagas/parasitologia , Parasitemia/parasitologia , Trypanosoma cruzi/patogenicidade , Animais , Brasil , Criança , DNA de Protozoário/genética , Modelos Animais de Doenças , Feminino , Genótipo , Humanos , Camundongos , Parasitemia/patologia , Trypanosoma cruzi/enzimologia , Trypanosoma cruzi/genética , Trypanosoma cruzi/isolamento & purificação , VirulênciaRESUMO
Species of the Lychnophora genus are plants native to Brazil, popularly known as "Brazilian arnica" and used in folk medicine as alcoholic and hydro-alcoholic preparations for the treatment of bruises, inflammation, pain, rheumatism and insect bites. The present study aimed to evaluate the safety of the use of Lychnophora pinaster Mart., Asteraceae. Acute toxicity of the crude ethanolic extract was evaluated by administration of the extract by oral route to male and female Swiss mice. A single extract dose of 125, 250 or 500 mg/kg was administered and the effects on spontaneous locomotor activity, exploratory behavior, muscle strength, body weight, food and water consumption, relative organ weight, histology, as well as hematological and biochemical parameters were evaluated. The three doses administered to the animals did not cause muscle tone alterations, but doses of 250 and 500 mg/kg induced a significant inhibition of the spontaneous locomotor activity and exploratory behavior of the animals in open-field test. There was no alteration to hematological parameters and consumption of water and food, body weight variation and organs relative weight. Changes were observed in AST and ALT during assessment of biochemical parameters. The histopathological evaluation showed that the extract provoked cellular alterations, such as vacuolar degeneration and inflammation in kidneys and liver at all doses. Liver morphometric analyses of male and female mice showed that the extract did not have dose-dependent effects. Although females showed a significant increase in inflammatory cells, the effect was not dose-dependent.