Browsing by Author "Arantes, Jerusa Marilda"

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    Increase of reactive oxygen species by desferrioxamine during experimental Chagas' disease.
    (2010) Francisco, Amanda Fortes; Vieira, Paula Melo de Abreu; Arantes, Jerusa Marilda; Silva, Maísa; Pedrosa, Maria Lúcia; Santos, Silvana Maria Elói; Martins Filho, Olindo Assis; Carvalho, Andréa Teixeira de; Araújo, Márcio Sobreira Silva
    Oxidative stress is common in inflammatory processes associated with many diseases including Chagas’ disease. The aim of the present study was to evaluate, in a murine model, biomarkers of oxidative stress together with components of the antioxidant system in order to provide an overview of the mechanism of action of the iron chelator desferrioxamine (DFO). The study population comprised 48 male Swiss mice, half of which were treated daily by intraperitoneal injection of DFO over a 35-day period, while half were administered sterile water in a similar manner. On the 14th day of the experiment, 12 DFO-treated mice and an equal number of untreated mice were experimentally infected with Trypanosoma cruzi. Serum concentrations of nitric oxide and superoxide dismutase and hepatic levels of total glutathione, thiobarbituric acid reactive species and protein carbonyl, were determined on days 0, 7, 14 and 21 post-infection. The results obtained revealed that DFO enhances antioxidant activity in the host but also increases oxidative stress, indicating that the mode of action of the drug involves a positive contribution to the host together with an effect that is not beneficial to the parasite.
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    Influência da utilização da desferrioxamina, quelante de ferro, sobre o curso da infecção pelo Trypanosoma cruzi em camundongos.
    (Programa de Pós-Graduação em Ciências Biológicas. Núcleo de Pesquisas em Ciências Biológicas, Pró-Reitoria de Pesquisa e Pós Graduação, Universidade Federal de Ouro Preto., 2006) Arantes, Jerusa Marilda; Carneiro, Cláudia Martins
    Utilizaram-se camundongos Swiss machos com trinta dias de idade, divididos em quatro grupos experimentais: (1) controle não-tratado - CNT; (2) controle tratado - CT; (3) infectado com a cepa Y do T. cruzi e não-tratado - INT e (4) infectado com a cepa Y do T. cruzi e tratado - IT. Os animais tratados receberam 5mg/animal/dia de Desferrioxamina (DFA) durante os 14 dias que precederam a infecção (500 formas sanguíneas da cepa Y do T. cruzi via intraperitoneal). Após a infecção, o grupo IT recebeu DFA por mais 21 dias. Nos grupos infectados, tratados ou não, avaliaram-se a curva de parasitemia diária, período pré-patente, patente, pico de parasitemia, dia do pico de parasitemia, taxa de mortalidade, e nos animais que sobreviveram à fase aguda da infecção, hemocultura, PCR e ELISA. Nos quatro grupos experimentais foram realizadas a dosagem de ferro no fígado, ferro sérico e hemoglobina. Avaliou -se também o peso dos animais, o peso relativo do coração, fígado, baço e linfonodo e as alterações histopatológicas, bem como o parasitismo tecidual nestes órgãos. Os animais foram necropsiados no 14 o e 21 o dia após a infecção (DAI). No grupo IT, a média dos níveis de parasitemia, a taxa de mortalidade apresentaram-se menores em relação ao grupo INT. Não foram observadas diferenças significativas no período pré patente. O pico de parasitemia no grupo INT foi no 11 o dia e no grupo IT no 10 o . O período patente no grupo INT (11 dias) foi significativamente menor que no grupo IT (21 dias). Cinco animais do grupo IT e 1 animal do grupo INT sobreviveram à infecção. Todos os animais tratados apresentaram hemocultura negativa na fase aguda e crônica da infecção enquanto o animal não-tratado apresentou hemocultura positiva nas duas fases. A PCR apresentou-se positiva em todos os animais tratados avaliados aos 60 DAI e 3 destes apresentaram PCR negativa aos 240 DAI. O animal infectado e nãotratado apresentou PCR positiva aos 60 e 240. Todos os animais apresentaram ELISA positiva aos 60 e 240 DAI. Os animais infectados apresentaram menores níveis de ferro no fígado que os animais não-infectados no 14 o e 21 o DAI. Os animais do grupo INT apresentaram maiores concentrações de ferro sérico quando comparados aos animais dos grupos CNT e IT no 21 o DAI. No 14 o DAI, os animais do grupo IT apresentaram níveis mais baixos de hemoglobina quando comparados ao grupo CT. O tratamento com a DFA reduziu o peso corporal dos animais infectados ou não. Entre o 14 o e 21 o DAI, observou-se aumento de peso relativo do coração, baço, fígado e linfonodo apenas no grupo INT. Os animais infectados, tratados ou não apresentaram alterações histológicas semelhantes no coração. O fígado dos animais do grupo IT, apresentou menor intensidade de alterações e a avaliação dos órgãos linfóides demonstrou resposta mais precoce no grupo IT . Não foram observadas diferenças em relação ao parasitismo tecidual nos órgãos analizados dos animais infectados, tratados ou não com DFA. Estes resultados demonstram que a diminuição dos níveis de ferro do hospedeiro contribui para a melhora do quadro clínico da infecção.
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    Trypanosoma cruzi : desferrioxamine decreases mortality and parasitemia in infected mice through a trypanostatic effect.
    (2011) Arantes, Jerusa Marilda; Francisco, Amanda Fortes; Vieira, Paula Melo de Abreu; Silva, Maísa; Araújo, Márcio Sobreira Silva; Carvalho, Andréa Teixeira de; Pedrosa, Maria Lúcia; Carneiro, Cláudia Martins; Tafuri, Washington Luiz; Martins Filho, Olindo Assis; Santos, Silvana Maria Elói
    Desferrioxamine (DFO) is a potent iron chelator that is also known to modulate inflammation and act as an efficient antioxidant under normal conditions and under oxidative stress. Many in vitro and in vivo studies have shown the efficacy of DFO in the treatment of viral, bacterial and protozoan infections. DFO is known to reduce the intensity of Trypanosoma cruzi infections in mice even during a course of therapy that is not effective in maintaining anaemia or low iron levels. To further clarify these findings, we investigated the action of DFO on mouse T. cruzi infection outcomes and the direct impact of DFO on parasites. Infected animals treated with DFO (5 mg/animal/day) for 35 days, beginning 14 days prior to infection, presented lower parasitemia and lower cumulative mortality rate. No significant effect was observed on iron metabolism markers, erythrograms, leukograms or lymphocyte subsets. In the rapid method for testing in vivo T. cruzi susceptibility, DFO also induced lower parasitemia. In regard to its direct impact on parasites, DFO slightly inhibited the growth of amastigotes and trypomastigotes in fibroblast culture. Trypan blue staining showed no effects of DFO on parasite viability, and only minor apoptosis in trypomastigotes was observed. Nevertheless, a clear decrease in parasite mobility was detected. In conclusion, the beneficial actions of DFO on mice T. cruzi infection seem to be independent of host iron metabolism and free of significant haematological side effects. Through direct action on the parasite, DFO has more effective trypanostatic than trypanocidal properties.
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    Trypanosoma cruzi : effect of benznidazole therapy combined with the iron chelator desferrioxamine in infected mice.
    (2008) Francisco, Amanda Fortes; Vieira, Paula Melo de Abreu; Arantes, Jerusa Marilda; Pedrosa, Maria Lúcia; Martins, Helen Rodrigues; Silva, Maísa; Veloso, Vanja Maria; Lana, Marta de; Bahia, Maria Terezinha; Tafuri, Washington Luiz; Carneiro, Cláudia Martins
    Iron chelators have been employed in various studies aimed at evaluating the relationship between the iron status of the host and the development of infection. In the present study, the effects of benznidazole (BZ) therapy in combination with the iron chelator desferrioxamine (DFO) on the development of infection in mice inoculated with Trypanosoma cruzi Y strain have been investigated. Infected mice treated with DFO presented lower levels of parasitemia compared with infected untreated animals. Therapy with BZ for 21 days, with or without DFO, led to decreased parasitemia and reduced mortality, but BZ in combination with DFO treatment for 35 days (BZ/DFO-35) gave 0% mortality. All infected groups presented lower levels of iron in the liver, but serum iron concentrations were greater in DFO-35 and BZ/DFO-35, whereas hemoglobin levels were higher in BZ/DFO-35 and lower in DFO-35 compared with other treated groups. The percentage cure, determined from negative hemoculture and PCR results in animals that had survived for 60 days post-infection, was 18% for BZ and BZ/DFO-35, 42% for BZ combined with DFO for 21 days, and 67% for DFO-35. The results demonstrate that modification in iron stores increases BZ efficacy.
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    Trypanosoma cruzi : treatment with the iron chelator desferrioxamine reduces parasitemia and mortality in experimentally infected mice.
    (2007) Arantes, Jerusa Marilda; Pedrosa, Maria Lúcia; Martins, Helen Rodrigues; Veloso, Vanja Maria; Lana, Marta de; Bahia, Maria Terezinha; Tafuri, Washington Luiz; Carneiro, Cláudia Martins
    The effects of prolonged treatment with iron chelator (desferrioxamine) on the development of infection in mice inoculated with Y Trypanosoma cruzi were determined. Infected/treated mice presented lower levels of parasitemia and reduced mortality rate compared with infected/non-treated animals. The five out of twenty infected/treated mice that survived the acute phase of infection showed negative hemoculture and positive ELISA in the acute and chronic phases and positive PCR in the acute phase: in the chronic phase, three of the animals presented negative PCR. The single surviving infected/non-treated animal exhibited positive hemoculture, PCR and ELISA in both phases of infection. Infected groups presented lower levels of iron in the liver compared with treated/non-infected or non-treated/ non-infected animals. The serum iron levels of the infected/non-treated group were higher on the 21st day post-infection in comparison with control and infected/treated groups. These results suggest that decrease of iron in the host leads to T. cruzi infection attenuation.