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1.
Exp Parasitol ; 255: 108647, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37914151

RESUMEN

Chagas disease (CD) remains neglected and causes high morbidity and mortality. The great difficulty is the lack of effective treatment. The current drugs cause side effects and have limited therapeutic efficacy in the chronic phase. This study aims to fulfil some gaps in studies of the natural substance lychnopholide nanoencapsulated LYC-PLA-PEG-NC (LYC-NC) and free (Free-LYC): the activity in epimastigotes and amastigotes to determine its selectivity index (SI), the therapeutic efficacy in mice infected with Colombian Trypanosoma cruzi strain and insight of the mechanism of LYC-NC action on T. cruzi. The SI was obtained by calculation of the ratio between the IC50 value toward H9c2 cells divided by the IC50 value in the anti-T. cruzi test. Infected Swiss mice were treated with 2 and 12 mg/kg/day via intravenous and oral, respectively, and the therapeutic efficacy was determined. The IC50 of LYC-NC and Free-LYC for epimastigotes of T. cruzi were similar. Both were active against amastigotes in cell culture, particularly Free-LYC. The SI of LYC-NC and Free-LYC were 45.38 and 32.11, respectively. LYC-NC 2 and 12 mg/kg/day cured parasitologically, 62.5% and 80% of the animals, respectively, infected with a strain resistant to treatment. The fluorescent NC was distributed in the cardiomyocyte cytoplasm, infected or not, and interacted with the trypomastigotes. Together, these results represent advances in demonstrating LYC as a potent new therapeutic option for treating CD.


Asunto(s)
Enfermedad de Chagas , Nanocápsulas , Nitroimidazoles , Tripanocidas , Trypanosoma cruzi , Animales , Ratones , Nifurtimox/uso terapéutico , Nitroimidazoles/farmacología , Nitroimidazoles/uso terapéutico , Enfermedad de Chagas/tratamiento farmacológico , Poliésteres/farmacología , Poliésteres/uso terapéutico , Tripanocidas/farmacología , Tripanocidas/uso terapéutico
2.
Mem Inst Oswaldo Cruz ; 113(11): e180271, 2018 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-30365644

RESUMEN

BACKGROUND The infection led by Trypanosoma cruzi persists in mammalian tissues causing an inflammatory imbalance. Carvedilol (Cv), a non-selective beta blocker drug indicated to treat heart failure and antihypertensive has shown to promote antioxidant and immunomodulatory properties which might improve the inflammation induced by T. cruzi. OBJECTIVES Evaluate the role of Cv on the inflammatory response of C57BL/6 mice acutely infected with the Colombian strain of T. cruzi. METHODS Animals were infected with the Colombian strain of T. cruzi and treated with Cv (25 mg/kg/day), benznidazole (Bz) (100 mg/kg/day) or their combination. On the 28th day of infection and 23 days of treatment, the euthanasia occurred, and the heart preserved for histopathological, oxidative stress (SOD, catalase, TBARs, carbonylated proteins) and plasma (CCL2, CCL5, TNF, IL-10) analyses. Parasitaemia and survival were assessed along the infection. FINDINGS Cv decreased TBARs, but increased the mortality rate, the parasitaemia and the levels of CCL2, CCL5, catalase and the inflammatory infiltrate in the cardiac tissue. Bz led the reduction of the inflammatory infiltrate and circulating levels of oxidative stress and inflammatory mediators in the infected mice. MAIN CONCLUSIONS Our data suggest that Cv, in this experimental model using the Colombian strain of T. cruzi, caused damage to the host.


Asunto(s)
Antagonistas Adrenérgicos beta/farmacología , Carvedilol/farmacología , Enfermedad de Chagas/tratamiento farmacológico , Corazón/efectos de los fármacos , Nitroimidazoles/farmacología , Tripanocidas/farmacología , Trypanosoma cruzi/efectos de los fármacos , Enfermedad Aguda , Animales , Catalasa/análisis , Enfermedad de Chagas/parasitología , Enfermedad de Chagas/patología , Citocinas/sangre , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Masculino , Ratones Endogámicos C57BL , Miocardio/patología , Estrés Oxidativo/efectos de los fármacos , Parasitemia/parasitología , Carbonilación Proteica/efectos de los fármacos , Valores de Referencia , Reproducibilidad de los Resultados , Superóxido Dismutasa/análisis , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Factores de Tiempo , Trypanosoma cruzi/aislamiento & purificación
3.
Immunobiology ; 227(4): 152243, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35839730

RESUMEN

Inflammatory and regulatory cytokines play an important role in the immunopathogenesis of Trypanosoma cruzi infection. Interleukin (IL)-33 is a member of the IL-1 superfamily of cytokines whose expression/production is upregulated following pro-inflammatory stimulation to alert the immune system in response to tissue stress or damage. The aim of this study was to evaluate the inflammatory profile induced in cultured J774 cells stimulated or not with IL-33 (10 ng/mL), with live parasites (1 × 106 metacyclic trypomastigote forms) and/or total antigen, TcAg (100 µg/mL) and with both, IL-33 and TcAg/T. cruzi. The cultures were evaluated at 24 h and 48 h after addition of the stimuli. For this, the supernatants were collected for the measurement of TNF, IL-17, CCL2, and IL-10 by ELISA and of nitrite by the Griess method. TNF, IL-17, and CCL2 concentrations were elevated in the presence of TcAg or live T. cruzi parasites at 24 h, and the addition of IL-33 potentiated these effects at 48 h. In addition, the T. cruzi-amastigote forms reduced in those infected J774 cells stimulated with IL-33 at 48 h. In conclusion, the IL-33 elevated the production of the TNF, IL-17, and CCL2 in cultured J774 cells stimulated with T. cruzi and/or its antigen and reduced the intracellular parasites, providing impetus to new investigations on its potential actions on the parasite-induced inflammation.


Asunto(s)
Enfermedad de Chagas , Trypanosoma cruzi , Enfermedad de Chagas/parasitología , Citocinas , Humanos , Interleucina-17 , Interleucina-33
4.
Mem. Inst. Oswaldo Cruz ; 113(11): e180271, 2018. graf
Artículo en Inglés | LILACS | ID: biblio-976226

RESUMEN

BACKGROUND The infection led by Trypanosoma cruzi persists in mammalian tissues causing an inflammatory imbalance. Carvedilol (Cv), a non-selective beta blocker drug indicated to treat heart failure and antihypertensive has shown to promote antioxidant and immunomodulatory properties which might improve the inflammation induced by T. cruzi. OBJECTIVES Evaluate the role of Cv on the inflammatory response of C57BL/6 mice acutely infected with the Colombian strain of T. cruzi. METHODS Animals were infected with the Colombian strain of T. cruzi and treated with Cv (25 mg/kg/day), benznidazole (Bz) (100 mg/kg/day) or their combination. On the 28th day of infection and 23 days of treatment, the euthanasia occurred, and the heart preserved for histopathological, oxidative stress (SOD, catalase, TBARs, carbonylated proteins) and plasma (CCL2, CCL5, TNF, IL-10) analyses. Parasitaemia and survival were assessed along the infection. FINDINGS Cv decreased TBARs, but increased the mortality rate, the parasitaemia and the levels of CCL2, CCL5, catalase and the inflammatory infiltrate in the cardiac tissue. Bz led the reduction of the inflammatory infiltrate and circulating levels of oxidative stress and inflammatory mediators in the infected mice. MAIN CONCLUSIONS Our data suggest that Cv, in this experimental model using the Colombian strain of T. cruzi, caused damage to the host.


Asunto(s)
Humanos , Trypanosoma cruzi/patogenicidad , /uso terapéutico , Quimiocinas , Cardiopatías
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