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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% (LD 50 ) and 20% (LD 20 ) of the parasites was 0.072 and 0.031 mg/mL, respectively and for trypomastigotes was 0.047 and 0.015 mg/mL, respectively. The combined use of cordycepin and pentostatin resulted in a LD 50 and LD 20 for epimastigotes of 0.068 and 0.027 mg/mL, respectively, as well as 0.056 and 0.018 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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and causes severe cardiac and brain damage, leading to behavioral alterations in humans and animals. However, the mechanisms involved in memory impairment during T. cruzi infection remain unknown. It has long been recognized that the enzymatic activities of acetylcholinesterase (AChE) and Na + , K + -ATPase are linked with memory dysfunction during other trypanosomiasis. Thus, the aim of this study was to evaluate the involvement of cerebral AChE and Na + , K + -ATPase activities in the memory impairment during T. cruzi (Colombian strain) infection. A significant decrease on latency time during the inhibitory avoidance task was observed in animals infected by T. cruzi compared to uninfected animals, findings compatible to memory dysfunction. Moreover, the cerebral AChE activity increased, while the Na + , K + -ATPase decreased in T. cruzi infected compared to uninfected animals. Histopathology revealed mild to moderate multifocal gliosis in the cerebral cortex and light focal meningeal lymphoplasmacytic infiltrate, which may have contributed to memory loss. Based on these evidences, we can conclude that T. cruzi (Colombian strain) causes memory impairment in mice experimentally infected. Moreover, the changes in AChE and Na + , K + -ATPase activities may be considered a mechanism involved in disease pathogenesis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim of this study was to analyses nitric oxide, antioxidant status, and oxidative profile in the liver of laying hens naturally infected by Salmonella enterica subsp enterica serovar Gallinarum (S. Gallinarum). The nitrite/nitrate (NO x ), reactive oxygen species (ROS), thiobarbituric acid-reactive substances (TBARS), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities were measured in liver samples, as well the biomarkers of hepatic function (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), total protein and albumin levels measured in serum. NO x levels and CAT activity were reduced in hepatic tissue of infected hens. On the other hand, TBARS and ROS levels, GR, GPx and GST activities were higher in infected animals. On biomarkers of tissue damage, ALT, AST, GGT and total protein levels were higher in serum of infected hens, and showed decreased albumin levels. In summary, ROS and TBARS production lead to damage on the membrane lipids that alter activities of antioxidant enzymes CAT, GR, GPx and GSH, an adaptive response against S. Gallinarum infection, contributing to the pathophysiology and clinical signs of the disease., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Salmonella is a facultative intracellular pathogen that may cause foodborne gastroenteritis in humans and animals consisting of over 2000 serovars. The serovar Salmonella Gallinarum is an important worldwide pathogen of poultry. However, little is known on the mechanisms of pathogenesis of Salmonella in chickens. The aim of this study was to evaluate cholinesterase and myeloperoxidase activities in hepatic tissue of laying hens naturally infected by S. Gallinarum. Twenty positive liver samples for S. Gallinarum were collected, in addition to seven liver samples from healthy uninfected laying hens (control group). The right liver lobe was homogenized for analysis of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and myeloperoxidase (MPO), and the left lobe was divided into two fragments, one for histopathology and the other for Salmonella isolation. The results showed changes in AChE and BchE activity in the liver of infected laying hens compared to the control group (P < 0.05), i.e. reduced AChE and increased BChE activities in liver samples. Infected animals showed increased MPO activity compared to healthy animals (P < 0.05). Furthermore, the histopathological findings showed fibrinoid necrosis associated to the infiltration of lymphocytes, plasma cells, macrophages,heterophils in the liver of infected hens. These findings suggest that the inflammatory process was attenuated providing a pro-inflammatory action of both enzyme analyzed in order to reduce the free ACh, a molecule which has an anti-inflammatory action. Therefore, our results lead to the hypothesis that cholinesterase plays an important role on the modulation of immune response against S. Gallinarum with an inflammatory effect, contributing to the response against this bacterium. This study should contribute to a better understanding on the pathogenic mechanisms involved in laying hens infected by S. Gallinarum., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

This study aimed to investigate the effects of diphenyl diselenide (PhSe)2 to treat mice experimentally infected by Toxoplasma gondii on seric biomarkers of cardiac function (creatine kinase, creatine kinase MB, troponin, and myoglobin), and lactate dehydrogenase, as well as to evaluate the enzymatic activity of creatine kinase (CK) and adenylate kinase (AK) in heart tissue. For the study, 40 female mice were divided into four groups of 10 animals each: the group A (uninfected and untreated), the group B (uninfected and treated), the group C (infected and untreated) and the group D (infected and treated). The inoculation was performed with 50 cysts of T. gondii (ME-49 strain). Mice from groups B and D were treated at days 1 and 20 post-infection (PI) with 5 μmol kg(-1) of (PhSe)2 subcutaneously. On day 30 PI, the mice were anesthetized and euthanized for blood and heart collection. As a result, it was observed a decrease in AK activity (P < 0.01) in the heart samples of groups C and D compared to the group A. Cardiac CK increased in the group C compared to the group A (P < 0.01). CK levels increased in infected mice (the group C) compared to other groups (A and D). Regarding CK-MB level, there was a decrease in the group D compared to the group B, without statistical difference compared to control groups (A and C). It was observed an increase on myoglobin in groups C and D, differently of troponin, which did not show statistical difference (P < 0.05) between groups. Mice from the group C showed an increase in lactate dehydrogenase (LDH) levels compared to other groups (A, B, and D). Histopathological evaluation of heart samples revealed necrosis, hemorrhagic regions and inflammatory infiltrates in mice from the Group C, differently from the group D where animals showed only inflammatory infiltrates. Based on these results we conclude that the (PhSe)2 had a protective effect on the heart in experimental toxoplasmosis by modulating tissue and seric CK activity, and avoiding an increase on seric LDH levels, probably due to the antioxidant effect of this compound., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Salmonella Gallinarum is the etiologic agent of fowl typhoid that affects chickens and turkeys causing egg production drops, infertility, lower hatchability, high mortality, and as a consequence severe economic losses to the poultry industry. The alterations in NTPDase and adenosine deaminase (ADA) activities have been demonstrated in several inflammatory conditions; however, there are no data in the literature associated with this infection. Thus, the aim of this study was to evaluate the activities of NTPDase, 5'nucleotidase, and ADA in serum and hepatic tissue of laying hens naturally infected by Salmonella Gallinarum. Liver and serum samples were collected of 27 laying hens (20 S. Gallinarum infected and 7 uninfected). NTPDase and 5'-nucleotidase activities in serum were increased (P < 0.001) in infected animals to hydrolysis of substrate ATP, ADP and AMP. In addition, it was observed decreased (P < 0.001) in ADA activity in serum of laying hens naturally infected by S. Gallinarum; as well as increased (P < 0.001) ADA activity in liver tissue of infected laying hens. Histopathological analyses revealed that S. Gallinarum caused fibrinoid necrosis in liver and spleen associated with infiltrates of heterophils, macrophages, lymphocytes, and plasma cells. Considering that NTPDase and ADA are involved in the cell-mediated immunity, this study suggests that activities of these enzymes could be important biomarkers to determine the severity of inflammatory and immune responses in salmonellosis, contributing to clarify the pathogenesis of the disease., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

This study aimed to verify the effect of the treatment with A. satureioides essential oil (free and nanoencapsulated forms) and diminazene aceturate on hematological and biochemical variables in rats infected by Trypanosoma evansi. The 56 rats were divided into seven groups with eight rats each. Groups A, C and D were composed by uninfected animals, and groups B, E, F and G were formed by infected rats with T. evansi. Rats from groups A and B were used as negative and positive control, respectively. Rats from the groups C and E were treated with A. satureioides essential oil, and groups D and F were treated with A. satureioides nanoencapsulated essential oil. Groups C, D, E and F received one dose of oil (1.5 mL kg(-1)) during five consecutive days orally. Group G was treated with diminazene aceturate (D.A.) in therapeutic dose (3.5 mg kg(-1)) in an only dose. The blood samples were collected on day 5 PI for analyses of hematological (erythrocytes and leukocytes count, hemoglobin concentration, hematocrit, mean corpuscular and mean corpuscular hemoglobin concentration) and biochemical (glucose, triglycerides, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, urea and creatinine) variables. A. satureioides administered was able to maintain low parasitemia, mainly the nanoencapsulated form, on 5 days post infection. On the infected animals with T. evansi treated with A. satureioides essential oil (free and nanocapsules) the number of total leucocytes, lymphocytes and monocytes present was similar to uninfected rats, and different from infected and not-treated animals (leukocytosis). Treatment with A. satureioides in free form elevated levels of ALT and AST, demonstrating liver damage; however, treatment with nanoencapsulated form did not cause elevation of these enzymes. Finally, treatments inhibited the increase in creatinine levels caused by infection for T. evansi. In summary, the nanoencapsulated form showed better activity on the trypanosome; it did not cause liver toxicity and prevented renal damage., (Copyright © 2014 Elsevier Inc. All rights reserved.)