RESUMO
The aim of this study was to evaluate in vitro the efficacy of cordycepin and pentostatin (alone or combined) against Trypanosoma cruzi, as well as the therapeutic efficiency of protocols of cordycepin and pentostatin combinations in mice experimentally infected with T. cruzi. In vitro, the cordycepin (3'-deoxyadenosine) and pentostatin (deoxycoformycin) exerted potent trypanocidal effect against T. cruzi (Colombian strain), similarly to benznidazole, which is the reference drug. For epimastigotes, the lethal dose of cordycepin capable of killing 50% (LD50) and 20% (LD20) of the parasites was 0.072 and 0.031â¯mg/mL, respectively and for trypomastigotes was 0.047 and 0.015â¯mg/mL, respectively. The combined use of cordycepin and pentostatin resulted in a LD50 and LD20 for epimastigotes of 0.068 and 0.027â¯mg/mL, respectively, as well as 0.056 and 0.018â¯mg/mL for trypomastigotes, respectively. In vivo, the combined use of cordycepin and pentostatin did not show the expected curative effect, however it was able to control the parasitema in the peak period. In summary, the combination of cordycepin and pentostatin showed no curative effect in mice infected by T. cruzi, despite the in vitro reduction of epimastigotes and trypomastigotes.
Assuntos
Antiprotozoários/farmacologia , Doença de Chagas/tratamento farmacológico , Desoxiadenosinas/farmacologia , Pentostatina/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Análise de Variância , Animais , Antiprotozoários/efeitos adversos , Antiprotozoários/uso terapêutico , Doença de Chagas/parasitologia , Desoxiadenosinas/uso terapêutico , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Coração/efeitos dos fármacos , Dose Letal Mediana , Camundongos , Miocárdio/patologia , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/parasitologia , Nifurtimox/efeitos adversos , Nifurtimox/uso terapêutico , Nitroimidazóis/efeitos adversos , Nitroimidazóis/uso terapêutico , Dinâmica não Linear , Parasitemia/prevenção & controle , Pentostatina/uso terapêutico , Distribuição Aleatória , Análise de RegressãoRESUMO
The aim of this study was to evaluate the efficacy of 3'-deoxyadenosine and deoxycoformycin combination in the treatment of mice infected by T. cruzi, as well as to verify the influence of the treatment on purinergic enzymes. Heart and serum samples were collected from 60 mice (30 infected and 30 uninfected) at day 12 post-infection. To verify treatment efficacy, parasitemia was monitored, and the treatment with 3'-deoxy adenosine and deoxycoformycin combination was able to reduce it, but had no curative effect on mice. Seric activities of NTPDase (ATP and ADP substrate) and ADA were increased significantly in untreated mice infected by T. cruzi compared to the negative control, as well as mice treated with 3'-deoxyadenosine and deoxycoformycin (alone or combined) modulated the activity of NTPDase (ATP and ADP substrate), preventing them from increasing in infected animals (activity similar to healthy animals). Treatment with deoxycoformycin alone and associated with 3'-deoxyadenosine modulated the activity of ADA preventing them from increasing in infected animals. However, seric activities of ADA in mice treated with 3'-deoxyadenosine (cordycepin) alone does not modify the ADA activity compared with infected and non-treated mice. However, the 5'-nucleotidase activity decreased significantly in infected untreated animals and the same occurred in infected and treated animals with deoxycoformycin and 3'-deoxyadenosine. However, treatment with deoxycoformycin associated with 3'-deoxyadenosine preventing them from decreasing the 5'-nucleotidase activity. Therefore, we conclude that the treatments did not have curative success for mice infected by T. cruzi. However, the treatments were able to modulate the purinergic enzymes during the infection by T. cruzi, which may contribute to reduce the inflammatory damage in heart.
Assuntos
Antiprotozoários/uso terapêutico , Doença de Chagas/tratamento farmacológico , Desoxiadenosinas/uso terapêutico , Parasitemia/tratamento farmacológico , Pentostatina/uso terapêutico , Trypanosoma cruzi/efeitos dos fármacos , Adenosina Desaminase/metabolismo , Animais , Doença de Chagas/parasitologia , Quimioterapia Combinada , Feminino , Camundongos , Parasitemia/parasitologia , Pirofosfatases/metabolismoRESUMO
Coagulation disorders have been described in Chagas disease with thrombocytopenia as an important event. Several mechanisms may be related to this pathogenesis, such as enzymes of the purinergic system, purine, and receptors involved in the regulation and modulation of physiological events related to hemostasis. Therefore, the aim of this study was to evaluate the activities of E-NTPDase, E-5'nucleotidase, and ecto-adenosine deaminase (E-ADA) in platelets of mice experimentally infected by Trypanosoma cruzi. Twelve female mice were used, divided into two groups (n = 6): uninfected and infected. Mice of infected group were intraperitoneally inoculated with 104 trypomastigotes of T. cruzi (strain Y). On day 12 post-infection (PI), blood samples were collected for quantitation and separation of platelets. A significant reduction in the number of platelets of infected mice (P < 0.05) was observed. The activities of E-NTPDase (ATP and ADP substrates), E-5'nucleotidase, and E-ADA in platelets increased significantly (P < 0.05) in mice infected by T. cruzi compared with uninfected animals. A negative correlation (P < 0.01)was observed between the number of platelets and ATP hydrolysis (r = -0.64), and ADP hydrolysis (r = -0.69) by E-NTPDase. Therefore, there is a response from the purinergic system activating ecto-enzymes in platelets of mice T. cruzi infected, as a compensatory effect of thrombocytopenia.
Assuntos
Adenosina Desaminase/metabolismo , Plaquetas/metabolismo , Doença de Chagas/enzimologia , Proteínas de Protozoários/metabolismo , Trombocitopenia/enzimologia , Trypanosoma cruzi/enzimologia , Trifosfato de Adenosina/metabolismo , Animais , Plaquetas/patologia , Feminino , Camundongos , Trombocitopenia/parasitologia , Trombocitopenia/patologiaRESUMO
The aim of this study was to evaluate the activity of purinergic enzymes in lymphocytes and cardiac tissue of mice experimentally infected by Trypanosoma cruzi. Twelve female mice were used, divided into two groups (n = 6): uninfected and infected. On day 12 post-infection (PI), the animals were anesthetized and after euthanized, and samples were collected for analyses. Infected mice showed reduction in erythrocyte counts, hematocrit and hemoglobin concentration, as well as reduced number of total leukocytes in consequence of neutrophilia (P < 0.01). The number of monocytes increased in infected mice (P < 0.001), however the number of lymphocytes and eosinophils did not differ between groups (P > 0.05). The E-NTPDase (ATP and ADP substrate) and E-ADA activities in lymphocytes increased significantly in mice infected by T. cruzi (P < 0.01). In the heart, multiple pseudocysts containing amastigotes within cardiomyocytes were observed, as well as focally extensive severe necrosis associated with diffuse moderate to severe inflammatory infiltrate of lymphocytes. Although, the NTPDase activity (ATP and ADP substrate) in the cardiac homogenate did not differ between groups, a reduction on 5'-nucleotidase activity (P < 0.001) and an increase in the ADA activity in infected animals (P < 0.05) were observed. Thus, animals infected by T. cruzi experienced the disease, i.e., showed anemia, leucopenia, and heart lesions. Associated with this, purinergic enzymes showed altered activities, which might be related to the modulation of the inflammatory response.
Assuntos
Doença de Chagas/enzimologia , Linfócitos/enzimologia , Miócitos Cardíacos/enzimologia , Purinas/metabolismo , 5'-Nucleotidase/metabolismo , Adenosina/metabolismo , Difosfato de Adenosina/metabolismo , Monofosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Antígenos CD/metabolismo , Apirase/metabolismo , Doença de Chagas/patologia , Modelos Animais de Doenças , Feminino , Coração/parasitologia , Testes Hematológicos , Hidrólise , Camundongos , Miocárdio/patologia , Parasitemia/parasitologia , Trypanosoma cruzi/fisiologiaRESUMO
The aim of this study was to investigate the activities of important enzymes involved in the phosphoryl transfer network (adenylate kinase and creatine kinase (CK)), lactate dehydrogenase (LDH), respiratory chain complexes and biomarkers of cardiac function in rat experimentally infected by Trypanosoma evansi. Rat heart samples were evaluated at 5 and 15 days post-infection (PI). At 5 day PI, there was an increase in LDH and CK activities, and a decrease in respiratory chain complexes II, IV and succinate dehydrogenase activities. In addition, on day 15 PI, a decrease in the respiratory chain complex IV activity was observed. Biomarkers of cardiac function were higher in infected animals on days 5 and 15 PI. Considering the importance of the energy metabolism for heart function, it is possible that the changes in the enzymatic activities involved in the cardiac phosphotransfer network and the decrease in respiratory chain might be involved partially in the role of biomarkers of cardiac function of T. evansi-infected rats.
Assuntos
Metabolismo Energético/fisiologia , Regulação Enzimológica da Expressão Gênica/fisiologia , Miocárdio/enzimologia , Trypanosoma/classificação , Tripanossomíase/parasitologia , Animais , Biomarcadores , Transporte de Elétrons/fisiologia , Feminino , Ratos , Ratos Wistar , Tripanossomíase/metabolismoRESUMO
The aim of this study was to evaluate the relationship between testicular lesions and hormone levels in rats experimentally infected with Trypanosoma evansi. For that, the measurement of reproductive hormones, histopathology and biomarkers of cellular injury were carried out in twenty-four animals, which were divided into two groups with 12 animals each. Group A was the negative control, or uninfected, while group B was composed by animals infected with T. evansi. Both groups were divided again into two other subgroups (n=6), from which serum and testicular fragments were collected on days 5 (A1 and B1) and 15 (A2 and B2) post-infection (PI). The morphological analysis showed increased alterations of head and tail of sperm in infected rats when compared with those of the control group. A significant reduction (P<0.01) in the levels of LH, FSH, testosterone and estradiol, associated with an increase in cortisol, was observed in serum of group B when compared with negative control. Additionally, NOx, lipid peroxidation and protein oxidation were enhanced in testicles, indicating the occurrence of cellular lesion. On histopathology, it was possible to observe testicular degeneration, among other disorders in infected animals. Therefore, based on these results, it is possible to conclude that the experimental infection with T. evansi caused changes in the levels of the main hormones of male rats associated with cellular injury.
Assuntos
Espermatozoides/parasitologia , Testículo/parasitologia , Tripanossomíase/sangue , Animais , Biomarcadores/sangue , Modelos Animais de Doenças , Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Hidrocortisona/sangue , Hormônio Luteinizante/sangue , Masculino , Parasitemia , Progesterona/sangue , Ratos Wistar , Testículo/fisiopatologia , Tripanossomíase/fisiopatologiaRESUMO
The aim of this study was to evaluate the purine levels of lambs experimentally infected with Haemonchus contortus. A total of 12 healthy lambs were divided into two groups, composed of 6 animals each: Group A represented the healthy animals (uninfected), while in Group B the animals were infected with 15 000 larvae of H. contortus. Blood was drawn on days 15, 45 and 75 post-infection (PI) in order to perform the purine analysis (ATP, ADP, AMP, adenosine, inosine, hypoxanthine, xanthine and uric acid) by high pressure liquid chromatography (HPLC) in serum. On day 15 PI a significant (P<0·05) increase in the levels of ATP and inosine was observed in the infected animals, unlike the levels of ADP, adenosine, xanthine and uric acid which were reduced. On day 45 PI a significant (P<0·05) increase in the ATP and xanthine levels in infected animals was observed, contrasting with reduced levels of ADP and uric acid. Finally, on day 75 PI an increase occurred in the levels of ATP, adenosine and hypoxanthine in infected lambs, concomitant with a reduction in the levels of ADP and uric acid (P<0·05). These changes in purine levels may influence the inflammatory process and the pathological events.
Assuntos
Hemoncose/veterinária , Haemonchus , Purinas/sangue , Doenças dos Ovinos/parasitologia , Animais , Fezes/parasitologia , Hemoncose/sangue , Hemoncose/parasitologia , Masculino , Ovinos , Doenças dos Ovinos/sangueRESUMO
The goal of this study was to evaluate reproductive hormones in sera samples of female rats experimentally infected by Trypanosoma evansi during different phases of the estrous cycle. For that, 64 animals were divided into two groups: 24 rats for the control group (uninfected), and 40 animals were infected by T. evansi. These groups were divided into subgroups according to the time of infection (days 5 and 15 post-infection; PI) and the phase of the estrous cycle (proestrus, estrus, metestrus and diestrus). Serum was collected at days 5 and 15 PI and the levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), progesterone and estradiol were assessed by enzyme immunoassay technique. The concentration of nitrite/nitrate (NOx), advanced oxidation protein products (AOPP), and thiobarbituric acid reactive substances (TBARS) were measured in ovaries and uteruses in these same periods. Infected females showed significant decrease (P<0.05) of LH, FSH, estradiol and progesterone in different periods and phases of the estrous cycle when compared to uninfected rats. In addition, it was observed an increase in the concentration of NOx, AOPP, and TBARS in the ovaries, which is indicative of cell damage. Therefore, our experimental study showed that T. evansi infection in female rats may cause changes in LH, FSH, estradiol, and progesterone levels regardless of the time of infection or phase of the estrous cycle.
Assuntos
Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Progesterona/sangue , Tripanossomíase/sangue , Produtos da Oxidação Avançada de Proteínas/análise , Animais , Biomarcadores/análise , Cães , Ciclo Estral/sangue , Feminino , Nitratos/análise , Nitritos/análise , Ovário/química , Ovário/patologia , Parasitemia/sangue , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/análise , Útero/química , Útero/patologiaRESUMO
Lagochilascariosis is a zoonotic disease caused by the nematode Lagochilascaris sp., with the northern of Brazil representing 81.2% of all reports of the disease worldwide. The aim of this study was to report the first occurrence of feline lagochilascariosis in the State of Rio Grande do Sul, southern of Brazil. It was diagnosed through coproparasitologic exam and laboratorial identification of the nematodes.
Assuntos
Infecções por Ascaridida/veterinária , Ascaridídios/classificação , Doenças do Gato/parasitologia , Animais , Antiparasitários/uso terapêutico , Infecções por Ascaridida/tratamento farmacológico , Infecções por Ascaridida/epidemiologia , Infecções por Ascaridida/parasitologia , Infecções por Ascaridida/cirurgia , Brasil/epidemiologia , Doenças do Gato/tratamento farmacológico , Doenças do Gato/epidemiologia , Doenças do Gato/cirurgia , Gatos , Feminino , Ivermectina/uso terapêutico , MasculinoRESUMO
This study aimed to evaluate the susceptibility of Brazilian isolates of Trypanosoma evansi to suramin sodium. For this purpose, three isolates of T. evansi (LPV-2005, LPV-2009 and LPV-2010) and seventy mice were used, with the animals divided in 10 groups (A, B, C, D, E, F, G, H, I and J) with seven animals each group. Mice of groups A, B, and C were infected with LPV-2005; Groups D, E and F with LPV-2009 and the groups G, H and I with LPV-2010. The group J was composed by healthy mice or uninfected. The parasitemia was monitored daily through blood smear, and the treatment of all groups was performed three days post-infection (PI), when all mice showed increased parasitemia. Groups A, D and G represented the positives controls, while groups B, E and H received a single dose of suramin sodium at 10 mgkg(-1) intramuscularly. Groups C, F and I were treated with three doses of suramin sodium at 10 mgkg(-1), respecting an interval of 24 h between each dose. Negative blood smears from all animals were obtained 24 h after treatment (AT), status maintained until the end of the experiment (50 days PI). The specific PCR for T. evansi was carried out from blood, showing negative results AT. Therefore, this study showed that a single dose of suramin sodium at 10 mgkg(-1) has the same efficacy of three doses, as recommended by the therapeutic literature. Furthermore, we observed that Brazilian isolates did not show resistance to the drug.