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The aim of this study was to evaluate the effect of treatment with liposomal (L-DMZ) and conventional (C-DMZ) diminazene aceturate formulations on hepatic and renal functions of rats, experimentally infected with Trypanosoma evansi. For this purpose, 72 Wistar rats (Rattus norvegicus) were divided into six groups (A, B, C, D, E, and F). Each group was subdivided into two other subgroups in order to assess the biochemical and histological results on days 7 and 40 post-treatment (PT). Treatments were carried out based on two different therapeutic protocols: L-DMZ and C-DMZ at 3.5mg/kg(-1), single dose (groups C and D), and five successive doses within intervals of 24h (groups E and F). Groups A and B corresponded to uninfected and infected (without treatment) animals, respectively. Sample collections were held on days 7 and 40 PT for the assessment of hepatic [alkaline phosphatase (AP), alanine transferase (ALT), albumin, gamma glutamil transferase (GGT) and renal functions (creatinine and urea). Additionally, the histology of fragments of liver, kidney, and spleen was performed. Animals in group B showed a significant increase in AP, GGT, ALT, and urea when compared with group A. On day 7 post-inoculation (PI), the biochemical analysis showed a reduction (P<0.05) of AP and GGT, while the levels of urea were increased in groups C, D, E, F. On day 40 PT, ALT was increased in these same groups when compared with group A. In histopathology, changes in liver samples were observed on day 7 PT in groups D and F, especially regarding the area and density of the hepatocytes. Renal analysis exhibited changes in glomerular space, glomerular, and corpuscular areas in group E. Therefore, these results allowed us to conclude that the treatment with L-DMZ and C-DMZ led to variable biochemical changes, which defined the functions of the liver and kidneys of treated animals, since the main histopathology alterations were observed in animals treated with liposomes, at their higher dosages. Thus, treatments with L-DMZ and C-DMZ in five consecutive doses were effective although being followed by liver toxicity., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

This study aimed to evaluate the effect of tea tree oil (TTO - Melaleuca alternifolia) on hepatic and renal functions, and the immune response of rats infected by Trypanosoma evansi. A pilot study has shown that rats treated with TTO orally (1 ml kg(-1)) had increased survival rate without curative effect. In order to verify if increased longevity was related to a better immune response against T. evansi when using tea tree oil, a second experiment was conducted. Thus, twenty-four rats were divided into four groups. The groups A and B were composed of uninfected animals, and the groups C and D had rats experimentally infected by T. evansi. Animals from the groups B and D were treated orally with TTO (1 ml kg(-1)) for three days. Blood samples were collected to verify humoral response analysis for immunoglobulins (IgA, IgM, IgE, and IgG) and cytokines (TNF-α, INF-γ, IL-1, IL-6, IL-4, and IL-10) at days 0, 3, 5 and 15 post-infection (PI). TTO treatment caused changes in the immunoglobulins and cytokines profile, as well as the course of T. evansi infection in rats. It was found that the TTO was not toxic, i.e., hepatic and renal functions were not affected. Therefore, it is possible to conclude that TTO influences the levels of inflammatory mediators and has trypanocidal effect, increasing life expectancy of rats infected by T. evansi., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The aim of this study was to evaluate the anti-trypanosomal effect of treatment with 3'-deoxyadenosine (cordycepin) combined with deoxycoformycin (pentostatin: inhibitor of the enzyme adenosine deaminase) in vitro by using mice experimentally infected with Trypanosoma evansi. In vitro, a dose-dependent trypanocidal effect of cordycepin was observed against the parasite. In the in vivo trials, the two drugs were used individually and in combination of different doses. The drugs when used individually had no curative effect on infected mice. However, the combination of cordycepin (2 mg kg-1) and pentostatin (2 mg kg-1) was 100% effective in the T. evansi-infected groups. There was an increase in levels of some biochemical parameters, especially on liver enzymes, which were accompanied by histological lesions in the liver and kidneys. Based on these results we conclude that treatment using the combination of 3'-deoxyadenosine with deoxycoformycin has a curative effect on mice infected with T. evansi. However, the therapeutic protocol tested led to liver and kidney damage, manifested by hepatotoxicity and nephrotoxicity.

The aim of this study was to evaluate the activity of delta-aminolevulinate dehydratase (δ-ALA-D) in red blood cells of rats infected with Trypanosoma evansi and establish its association with haematocrit, serum levels of iron and zinc and lipid peroxidation. Thirty-six male rats (Wistar) were divided into 2 groups with 18 animals each. Group A was non-infected while Group B was intraperitoneally infected, receiving 7·5×106 trypomastigotes per animal. Each group was divided into 3 subgroups of 6 rats and blood was collected during different periods post-infection (p.i.) as follows: day 5 (A1 and B1), day 15 (A2 and B2) and day 30 PI (A3 and B3). Blood samples were collected by cardiac puncture to estimate red blood cell parameters (RBC), δ-ALA-D activity and serum levels of iron, zinc and thiobarbituric acid reactive substances (TBARS). Rats in group B showed a significant (P<0·05) reduction of RBC count, haemoglobin concentration and haematocrit at days 5 and 15 p.i. The activity of δ-ALA-D in blood was significantly (P<0·001) increased at days 15 and 30 p.i. δ-ALA-D activity in blood had a significant (P<0·05) negative correlation with haematocrit (r=-0·61) and haemoglobin (r=-0·70) at day 15 p.i. There was a significant (P<0·05) decrease in serum iron and zinc levels and an increase in TBARS levels (P<0·05) during infection. The δ-ALA-D activity in blood was negatively correlated with the levels of iron (r=-0·68) and zinc (r=-0·57) on day 30 p.i. It was concluded that the increased activity of δ-ALA-D in blood might have occurred in response to the anaemia in remission as heme synthesis was enhanced.

The aim of this study was to measure the levels of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin 1 (IL-1) and interleukin 6 (IL-6) in the serum of rats experimentally infected with Trypanosoma evansi and to correlate these levels with hematological parameters. Initially, 48 rats (group T) were intraperitoneally inoculated with cryopreserved blood containing 1×10(6) trypomastigotes per animal. Twenty-eight animals (group C) were used as negative controls and received 0.2 mL of saline by the same route. The experimental groups were formed according to the time after infection and the degree of parasitemia as follows: four control subgroups (C3, C5, C10 and C20) with seven non-inoculated animals each and four test subgroups (T3, T5, T10 and T20) with 10 animals each inoculated with T. evansi. The blood samples were collected by cardiac puncture at days 3 (C3, T3), 5 (C5, T5), 10 (C10, T10) and 20 (C20, T20) post-infection (PI) to perform the complete blood count and the determination of IFN-γ, TNF-α, IL-1 and IL-6 levels using an ELISA quantitative sandwich. Infected rats showed normocytic normochromic anemia during the experimental period. T. evansi infection in rats caused a serum increase (P<0.01) of IFN-γ, TNF-α, IL-1 and IL-6 levels at days 3, 5, 10 and 20 PI compared to the controls. The multiple linear regressions showed a reduction of 24% in the hematocrit as a consequence of the increased IFN-γ, TNF-α and IL-1. Therefore, we conclude that the infection caused by T. evansi causes an increase in the pro-inflammatory cytokines. These results suggest a synergism among IL-1, TNF-α and IFN-γ contributing to the development of anemia. This increase is associated with the regulation of immune responses against the parasite., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The existence of cholinergic receptors in the immune system cells is well documented. This study aimed to evaluate the acetylcholinesterase activity (AChE) in lymphocytes from rats infected with Trypanosoma evansi in acute and chronic phase disease. Twenty animals were infected with 10(6) trypomastigotes forms each and 10 were used as negative controls. The two groups of inoculated rats were formed according to the degree of parasitemia and the period post-infection (PI). Group A: rats with 4 days PI and between 24 and 45 parasites/field (1000×); group B: rats with 30 days PI and parasitemia with jagged peaks between 0 and 1 parasites/field; group C: not-infected animals. At 4 days PI (acute phase) and 30 days PI (chronic phase) the rats were anesthetized to collect blood for hemogram and separation of lymphocytes. After separation, the AChE activity was measured in lymphocytes. It was observed that the number of lymphocytes increased significantly in group A compared to group C. The activity of AChE in lymphocytes significantly increased in acute phase and decreased in chronic phase in the infected rats when compared to not-infected (P<0.05). Statistical analysis showed a positive correlation between the number of lymphocytes and AChE activity in lymphocytes in 4 days PI (r(2): 0.59). Therefore, the infection by T. evansi influences AChE activity in lymphocytes of rats indicating changes in the responses of cholinergic system in acute phase, possibly due to immune functions performed by these enzymes., (Copyright © 2010 Elsevier Inc. All rights reserved.)