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Efficacy of combined therapy of benzonidazole and SAL de ANGELI (Na2N2O3) in the murine model of acute and chronic Chagas disease.
Universidade Estadual de Londrina (UEL)
Department of Pathological Sciences
Phileno Pinge Filho
Phileno Pinge Filho
Type of Research Project
- Basic science
What is the background of the project?
The Nifurtimox and Benzonidazole (BZ) drugs are used in the treatment of Chagas disease (CD) since the 70 years. Both can induce side effects in patients and have low efficacy in the chronic phase. Therefore, it is necessary to identify more efficient and less toxic medications for the treatment of CD. Different studies have already shown the positive and negative effects of nitric oxide (NO) donors, such as ruthenium (RU) Donor of NO and indometacin-No on the course of Trypanosoma cruzi infection. It has been shown that the association of RU-BZ-NO (RUBZNO2) has increased the action of BZ in the model of the murine infection by T. cruzi.
What is the aim of the project?
To evaluate the efficacy of the combined treatment of BZ and ANGELI Salt (Na2N2O3), donor of HNO (Nitroxil), on the acute and chronic phase of the experimental CD.
What techniques and methods are used?
Mice Balb/C and C57BL/6 (Models of susceptibility and resistance to T. cruzi strain Y) will be infected with blood tripomastigotes forms; 5 X 103 for acute phase studies and 102 for chronic phase studies. The animals will be divided into different control and experimental groups. In the acute phase studies, three days after infection, the animals will be subjected to the following treatments: Group Na2N2O3, the animals receive Intraperitoneal route (60 & #924; MG/KG/day); BZ Group, the animals will receive BZ (25 MG/KG/day); Group BZ + Na2N2O3 the animals will receive BZ (25 MG/kg/day together with 60 & #924; MG/kg of Na2N2O3). The Na2N2O3 will be dissolved in NaOH 10 MM and diluted in saline solution 0.9%, BZ will be dissolved in saline solution 0.9%. The animals of the control groups will only receive saline solution by the same route. For phase Studies Chronic, the control and experimental groups cited above will receive the same treatments starting 90 days after the infection. In both studies, the parasitic load will be determined in the Blood and heart, dosage of nitric oxide and pro-inflammatory cytokines in plasma during the course of infection (acute phase and chronic phase). We will also evaluate the effect of treatments on anemia, oxidative stress and alterations in cardiovascular parameters occurring in the acute phase of infection, cording with progression to the chronic phase. We also intend to evaluate the effects of treatments on epimastigotes, trypomastigotes and amastigotes forms, determining the cytotoxicity of drugs and influence on the capacity of invasion and survival of the parasite inside macrophages. We hope the SAL of ANGELI association with lower doses of BZ may increase the trypanocidal activity and decrease the toxic effects of BZ.
What is the role of the student?
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
The student will receive instructions and orientations on the everyday activities of the laboratory and the techniques that are used in the project. It is expected the student study about Chagas disease before and during the internship. Besides, the student will accompany the experiments of cell culture and infection by Trypanosoma cruzi in the murine model, making a comparison between Chagas disease in the acute and chronic phases. The student should conduct seminars, at the end of the intership, based on learning during the exchange.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Yes. The tutor will indicate scientific articles produced by the laboratory itself at the beginning of the internship
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a presentation - The student will prepare a scientific report
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Determination and interest in learning.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months) - Pre-Medical students from the American-British system - Students in biomedical fields - Dental medicine students (IADS members)
- Nitric oxide-releasing indomethacin enhances susceptibility to Trypanosoma cruzi infection acting in the cell invasion and oxidative stress associated with anemia. - Tatakihara VL; Malvezi AD; Panis C; Cecchini R; Zanluqui NG; Yamauchi LM; Martins MI; da Silva RV; Yamada-Ogatta SF; Rizzo LV; Martins-Pinge MC; Pinge-Filho P. - Chem Biol Interact. 2015 Feb 5;227:104-11. doi: 10.1016/j.cbi.2014.12.024. Epub 2015 Jan 2. - PMID: 25559858
- Antimicrobial activity of synthetic bornyl benzoates against Trypanosoma cruzi. - Corrêa PR; Miranda RR; Duarte LP; Silva GD; Filho SA; Okuma AA; Carazza F; Morgado-Díaz JA; Pinge-Filho P; Yamauchi LM; Nakamura CV; Yamada-Ogatta SF
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