New method for quantification of Trypanosoma cruzi in animal’s tissue in the chronic phase of experimental Chagas' disease

Esperandim, Viviane Rodrigues; Ferreira, Daniele da Silva; Toldo, Míriam Paula Alonso; Saraiva, Juliana; Augusto, Mariana Bryan; Albuquerque, Sérgio de

doi:10.1007/s00436-010-1780-7

Cited by 7 publications

(6 citation statements)

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“…The current available drugs are effective in the acute phase of the disease and act against amastigotes of some strains of T. cruzi in late acute, indeterminate, and chronic phases of Chagas disease. But they do not exhibit activity against the Y strain of T. cruzi during the later phases . So, the purpose of this work was to evaluate the effect of NFOH in several tissues (heart, colon, liver, kidney, spleen, brain and skeletal muscle) during the indeterminate form of the disease, induced by the Y strain of T. cruzi in BALB/c male mice.…”

Section: Introductionmentioning

confidence: 99%

“…But they do not exhibit activity against the Y strain of T. cruzi during the later phases. [25][26][27][28][29][30][31][32][33][34][35] So, the purpose of this work was to evaluate the effect of NFOH in several tissues (heart, colon, liver, kidney, spleen, brain and skeletal muscle) during the indeterminate form of the disease, induced by the Y strain of T. cruzi in BALB/c male mice.…”

Section: Introductionmentioning

confidence: 99%

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Hydroxymethylnitrofurazone treatment in indeterminate form of chronic Chagas disease: Reduced intensity of tissue parasitism and inflammation—A histopathological study

Scarim

Andrade

Rosa

et al. 2018

Int J Experimental Path

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Summary Hydroxymethylnitrofurazone (NFOH) is a nitrofurazone prodrug effective in vivo during acute infections, and it has less hepatotoxicity effect than the standard drug benznidazole (BZN) which has been used during short‐ and long‐term treatment. In the present study, we induced the indeterminate form of Chagas disease in mice with a Y strain of Trypanosoma cruzi and analysed the histopathological data about the effects of NFOH and BZN on different tissues, including the heart, skeletal muscle, liver, kidney, colon, spleen and brain. After infection, BALB/c mice were treated with NFOH (150 mg/kg) and BZN (60 mg/kg) for 60 days and then submitted to immunosuppression using dexamethasone (5 mg/kg) for 14 days. Two trained analysts, as part of a blind evaluation, examined the results using serial sections of 3 mm diameter in two different moments. The results showed reactivation of the disease only in the infected nontreated group (POS). After treatment, amastigote nests were found in the heart, colon, liver and skeletal muscle in the POS group and in the heart and liver of the BZN group. Interestingly, amastigote nests were not found in the NFOH and NEG groups. The histopathological analysis showed fewer tissue lesions and parasite infiltrates in the NFOH group when compared with the BZN and POS groups. We have not observed any increase in the levels of hepatocellular injury biomarkers (AST/ALT) in the NFOH group. These in vivo studies show the potential for NFOH as an effective and safe compound useful as an anti‐T. cruzi agent.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hydroxymethylnitrofurazone treatment in indeterminate form of chronic Chagas disease: Reduced intensity of tissue parasitism and inflammation—A histopathological study

Scarim

Andrade

Rosa

et al. 2018

Int J Experimental Path

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“…After the treatment period (20 days), the rate of parasitism tissue was determined in the heart, spleen, and liver of the animals, according to Esperandim et al (2010). The organs were collected at the end of treatment.…”

Section: Quantitative Determination Of T Cruzi By Characterization Omentioning

confidence: 99%

Reduction of parasitism tissue by treatment of mice chronically infected with Trypanosoma cruzi with lignano lactones

et al. 2010

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The reduction of parasitism tissue upon treatment with two lignano lactones, namely (-)- cubebin (CUB) and (-)-hinokinin (HNK), was evaluated in the chronic phase of Chagas' disease by quantifying the enzyme beta-galactosidase expressed by the CL B5 clone strain of Trypanosoma cruzi. Tissue karyometry was also performed. Treatment with the assessed lignans led to a larger reduction in parasitism tissue in all evaluated organs, compared with benznidazole (BZN). Oral treatment with CUB or HNK was more effective. Karyometry results demonstrated that the infected control animals had increased nuclear area compared with uninfected controls, indicating cellular hypertrophy. Results also revealed that use of CUB or HNK was able to significantly prevent this increase, and a slight decrease in the nuclear area was observed, compared with mice treated with BZN. Taken together, these data demonstrate that CUB and HNK could be considered as potential compounds for the development of new drugs for treatment of Chagas' disease.

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“…To address this issue, we have developed an assay that measures the ability of compounds to alter in vivo parasite growth using whole animal imaging (Figure 3; 30 . Previous investigators have used T. cruzi lines expressing luciferase 38 or betagalactosidase 39 to track parasite growth and persistence in T. cruzi infection. To determine if reporter gene-expressing parasites could be used to more quickly evaluate treatment efficacy, T. cruzi lines expressing luciferase or tdTomato protein were injected into the footpads of mice, and parasite growth was monitored in this site with or without treatment.…”

Section: In Vivo Drug Screening and Testingmentioning

confidence: 99%

Methodological advances in drug discovery for Chagas disease

Bustamante

Tarleton

2011

Expert Opinion on Drug Discovery

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Introduction Chagas disease is the highest impact human infectious disease in Latin America, and the leading worldwide cause of myocarditis. Despite the availability of several compounds that have demonstrated efficacy in limiting the effects of T. cruzi, these compounds are rarely used due to their variable efficacy, substantial side effects and the lack of methodologies for confirming their effectiveness. Furthermore, the development of more efficacious compounds is challenged by limitations of systems for assessing drug efficacy in vitro and in vivo. Areas covered Herein, the authors review the development of Chagas disease drug discovery methodology, focusing on recent developments in high throughput screening, in vivo testing methods and assessments of efficacy in humans. Particularly, this review documents the significant progress that has taken place over the last 5 years that have paved the way for both target-focused and high-throughput screens of compound libraries. Expert opinion The tools for in vitro and in vivo screening of anti-T. cruzi compounds have improved dramatically in the last few years and there are now a number of excellent in vivo testing models available; this somewhat alleviates the bottleneck issue of quickly and definitively demonstrating in vivo efficacy in a relevant host animal system. These advances emphasize the potential for additional progress resulting in new treatments for Chagas disease in the coming years. That being said, national and international agencies must improve the coordination of research and development efforts in addition to cultivating the funding sources for the development of these new treatments.

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New method for quantification of Trypanosoma cruzi in animal’s tissue in the chronic phase of experimental Chagas' disease

Cited by 7 publications

References 9 publications

Hydroxymethylnitrofurazone treatment in indeterminate form of chronic Chagas disease: Reduced intensity of tissue parasitism and inflammation—A histopathological study

Hydroxymethylnitrofurazone treatment in indeterminate form of chronic Chagas disease: Reduced intensity of tissue parasitism and inflammation—A histopathological study

Reduction of parasitism tissue by treatment of mice chronically infected with Trypanosoma cruzi with lignano lactones

Methodological advances in drug discovery for Chagas disease

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