Trypanosoma cruzi: Does the intake of nanoencapsulated benznidazole control acute infections?

Chagas Disease (CD) affects around eight million people worldwide. It is considered a neglected disease that presents few treatment options with efficacy only in the acute phase. Nanoparticles have many positive qualities for treating parasite infections and may be effectively and widely employed in clinical medicine. This research aimed to evaluate the nanoencapsulated benznidazole treatment in animals experimentally infected with Trypanosoma cruzi. To analyze the treatment efficacy, we evaluated survival during thirty days, parasitemia, genotoxicity, and heart and liver histopathology. Thirty-five female Swiss mice were organized into seven groups characterizing a dose curve: A - Negative control (uninfected animals), B - Positive control (infected animals), C - Benznidazole (BNZ) 100 mg/kg (infected animals), D - 5 mg/kg Benznidazole nanocapsules (NBNZ) (infected animals), E - 10 mg/kg Benznidazole nanocapsules (infected animals), F - 15 mg/kg Benznidazole nanocapsules (infected animals), G - 20 mg/kg Benznidazole nanocapsules (infected animals). The animals were infected with the Y strain of T. cruzi intraperitoneally. The treatment was administered for eight days by oral gavage. It was possible to observe that the treatment with the highest NBNZ dose presented efficacy similar to the standard benznidazole drug. The 20 mg/kg NBNZ dose was able to reduce parasitemia, increase survival, and drastically reduce heart and liver tissue damage compared to the 100 mg/kg BNZ dose. Moreover, it showed a lower DNA damage index than the BNZ treatment. In conclusion, the nanoencapsulation of BNZ promotes an improvement in parasite proliferation control with a five times smaller dose relative to the standard dose of free BNZ, thus demonstrating to be a potential innovative therapy for CD.

Comparing the efficacy of nutmeg essential oil and a chemical pesticide against Musca domestica and Chrysomya albiceps for selecting a new insecticide agent against synantropic vectors.

The insecticidal activity of Myristica fragrans (Houtt) essential seed oil, (Nutmeg) was evaluated against Musca domestica (Linnaeus) and Chrysomya albiceps (Wiedemann); both important infectious pathogenic disease vectors. The oil was extracted by distillation, and 21 components were identified during chemical analysis; principally ß-pinene (26%), α-pinene (10.5%), Sabinene (9.1%) and γ-terpinen (8.5%). Insecticidal properties were identified through larvicide and adulticide tests. Using the immersion method, the oil at 5% was found to be very effective (90 ± 1%) against M. domestica larvae. The results for adulticide activity varied by fly species, dosage, time, and method of exposure. Topical application (on the insect thorax) was more toxic to C. albiceps, where the lethal concentration at 50% (LC50) was 2.02 ± 0.56, and 8.57 ± 2.41 for the common flies. When the insects were exposed to oil impregnated paper, the results were similar for M. domestica and C. albiceps adults with respective LC50 values of 2.74 ± 0.24, and 3.65 ± 0.48. Thus, the results demonstrated that M. fragrans oil presents insecticidal activity and can be used for control of Musca domestica and Chrysomya albiceps.

Trypanosoma evansi impacts on embryonic neural progenitor cell functions.

Trypanosoma evansi appears to have a significant tropism for brain tissue in its chronic and acute phases. The most common symptoms of this brain infection are motor incoordination, meningoencephalitis, demyelination, and anemia. There have only been few studies of the effects of T. evansi infection on neuronal differentiation and brain plasticity. Here, we investigated the impact of the congenital T. evansi infection on brain development in mice. We collected telencephalon-derived neural progenitor cells (NPCs) from T. evansi uninfected and infected mice, and cultivated them into neurospheres. We found that T. evansi significantly decreased the number of cells during development of neurospheres. Analysis of neurosphere differentiation revealed that T. evansi infection significantly increased neural migration. We also observed that T. evansi promoted expression of glial fibrillary acidic protein (GFAP) in infected cells. These data suggest that congenital T. evansi infection may affect embryonic brain development.

Curcumin pre-treatment modulate the activities of adenine nucleotide and nucleoside degradation enzymes in lymphocyte of rats infected with Trypanosoma evansi.

This study aimed to evaluate nucleoside triphosphate diphosphohydrolase (NTPDase) and adenosine deaminase (ADA) activities in lymphocytes from rats supplemented or not with curcumin 30 days prior to experimental infection with Trypanosoma evansi. Thirty-two adult male Wistar rats were divided in four groups. The pre-infection group 20 (PreI20) received orally 20 mg/kg of curcumin and pre-infection group 60 (PreI60) received orally 60 mg/kg of curcumin for 30 days prior inoculation with T. evansi. The infected e non-infected control groups received only oral vehicle for 30 days. Trypanosoma evansi infected groups were inoculated intraperitoneally with 0.2 ml of blood with 1 × 106 parasites. After inoculation the treatment of the groups continued until the day of euthanasia (15 days). The results showed that curcumin pre-treatment, with both doses, reduced (P < .05) NTPDase and increased (P < .05) ADA activity in lymphocytes of treated groups when compared to untreated and infected animals (control). The results of this study support the evidence that the regulation of ATP and adenosine levels by NTPDase and ADA activities appear to be important to modulate the immune response in T. evansi infection, once the treatment with curcumin maintained the NTPDase activity reduced and enhanced ADA activity in lymphocytes. It is possible to conclude that the use of curcumin prior to infection with T. evansi induces immunomodulatory effects, favoring the response against the parasite.

Effects of resveratrol on the differentiation fate of neural progenitor cells of mouse embryos infected with Trypanosoma cruzi.

Chagas disease (CD) affecting about 7 million people is caused by the flagellate protozoan Trypanosoma cruzi. The central nervous system (CNS) is an important site for T. cruzi persistence in the host during the chronic phase of infection, because the protozoan may pass the blood-brain barrier and may cause motor and cognitive neuronal damage. Thinking about avoiding or minimizing these negative effects, it is hypothesized that resveratrol (RSV), a component with several medicinal properties has beneficial effects on the CNS. The objective of this study was to investigate, whether T. cruzi infection interferes with neurogenesis and gliogenesis of embryos of infected mice females, and whether RSV would be able to avoid or minimize these changes caused by CD. RSV is a polyphenol found in grapes and widely studied for its neuroprotective and antioxidant properties. In addition, we investigated the role caused by the parasite during congenital infection and CNS development. Embryos and their brains were PCR-positive for T. cruzi. For this study, NPCs obtained from telencephalon of infected and uninfected embryos and were cultured in presence of resveratrol for forming neurospheres. The results demonstrated that the congenital transmission of T. cruzi influences CNS formation and neural fate, decreasing the number of neuroespheres and causing an elongation in the phases of the cell cycle. In addition, the parasite promoted an increase in neugliogenesis. Resveratrol was neuroprotective and prevented negative effects of the infection. Thus, we suggest the use of resveratrol as a therapeutic target for the treatment of neuroinflammation or as neuroprotective agent during Chagas disease, as it improves gliogenesis and restores neural migration.

Cordycepin (3'-deoxyadenosine) and pentostatin (deoxycoformycin) against Trypanosoma cruzi.

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 0.031 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 LD50 and LD20 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.

Tissue oxidative damage mediates impairment on phosphotransfer network during thymol intake: Effects on hepatic and renal bioenergetics.

Recent evidences demonstrated that ingestion of several monoterpenes cause hepatic and renal damage due to impairment on mitochondrial energy production, eliciting a collapse on adenosine triphosphate (ATP) synthesis and consequently impairment on bioenergetic homeostasis. Thus, the aim of this study was to evaluate whether phosphotransfer network, catalyzed by creatine kinase (CK), adenylate kinase (AK), and pyruvate kinase (PK), can be a pathway to explain hepatic and renal bioenergetics homeostasis impairment due to thymol ingestion. Daily intake of thymol (40 mg/kg) significantly cause a decreased kidney weight and relative kidney weight compared to control group. The same dose of thymol inhibited renal cytosolic and mitochondrial CK activity as well as renal PK activity compared to control group. Finally, thymol (40 mg/kg) elicited a significant increase on renal reactive oxygen species and lipid damage levels, as well as an inhibition on antioxidant capacity against peroxyl radicals and non-protein thiol levels, which did not occur liver. Doses of 10 and 20 mg/kg of thymol administered orally for 30 consecutive days non-changed these variables. Based on these evidence, the data supported that intake of a high dose of thymol severely inhibits cytosolic and mitochondrial CK activity, a crucial enzyme to maintain cellular energy homeostasis. Moreover, high dietary thymol intake impaired communication between CK isoenzymes, which inhibits the attempts to regenerate ATP or to facilitate the CK/PCr shuttle to improve the intracellular ATP utilization and consumption. Moreover, the inhibition of renal CK and PK activities appears to be mediated by the renal oxidation of lipids and thiol groups, as well as by the reduction of the renal antioxidant capacity.

Blood-brain barrier breakdown, memory impairment and neurotoxicity caused in mice submitted to orally treatment with thymol.

Several evidences have related the biochemical and pharmacological properties of thymol, but the possible neurotoxic effects of this compound remain unknown and not evaluated. Thus, the purpose of this study was to evaluate whether intake of thymol in different doses (10, 20 and 40 mg/kg) induce neurotoxicity and behavioral alterations using mice as experimental model, as well as the involvement of blood-brain barrier (BBB) and brain neurotransmitters in these alterations. Thymol (20 and 40 mg/kg) significantly decrease latency time to inhibitory avoidance task when compared to control group, indicating a memory loss after 30 days of oral treatment. Also, thymol (20 and 40 mg/kg) induced a significant increase on BBB permeability to Evan's blue dye when compared to control group, which is an indicative of BBB breakdown. Moreover, a significant increase of brain acetylcholinesterase (AChE) was observed in mice treated with 40 mg/kg of thymol, while the activity of sodium-potassium pump (Na+, K+-ATPase) was inhibited in mice treated with 20 and 40 mg/kg thymol when compared to control group. Finally, mice that received 20 and 40 mg/kg thymol showed a significant increase on cerebral reactive oxygen species (ROS) levels and cerebral xanthine oxidase (XO) activity compared to control group. Based on these evidences, the rupture of BBB can be considered an important pathway linked in thymol-induced memory loss. Also, the augmentation of brain ROS levels elicited by increase on XO activity may be a via involved in the damage to BBB, and an oxidative pathway that impairs the activity of brain neurotransmitters, as AChE and Na+, K+-ATPase. In summary, the dose of 10 mg/kg thymol can be safe and without neurotoxic effects in a period of 30 days of intake.

In vitro Safety and Efficacy of Lavender Essential Oil (Lamiales: Lamiaceae) as an Insecticide Against Houseflies (Diptera: Muscidae) and Blowflies (Diptera: Calliphoridae).

Essential oils are considered an alternative for replacement of conventional insecticides that have provoked an increasing number of resistant species and damages to health. The objective of this work was to investigate the insecticidal activity of Lavandula dentata L. (Lamiales: Lamiaceae) oil against the species Musca domestica L. (Diptera: Muscidae) and Chrysomya albiceps Wiedemann (Diptera: Calliphoridae). Extraction of the essential oil from the aerial parts of the plant was carried out using hydro-distillation. Its principal compounds (1,8-cineol, camphor, and linalool oxide) were identified. Insecticidal activity was determined by evaluating adulticidal effect using topical application methods and exposure to impregnated paper; larvicidal effect was determined using immersion method. The essential oil presented toxicity in M. domestica and C. albiceps adults; the lethal concentration values (LC50) in the superficial application method were respectively 3.13 ± 0.64 and 1.39 ± 0.19% live weight (l/v). Toxicity was also found in the oil impregnated paper exposure test; the LC50 results for M. domestica and C. albiceps were respectively 4.15 ± 0.64 and 5.14 ± 0.81%. Larvicidal effect was observed on third stage M. domestica larvae when exposed to an oil concentration of 2.5% (m/v). In addition, the oil was evaluated for cytotoxicity, mutagenicity, and genotoxicity in human cells, and the in vitro safety of this oil in human cells was verified. Thus, L. dentata oil presented insecticidal activity in M. domestica and C. albiceps and can be used as an alternative for control of these dipterans.

Protective effect of nerolidol-loaded in nanospheres against cerebral damage caused by Trypanosoma evansi.

Trypanosoma evansi is a zoonotic parasite associated with high animal mortality that has gained importance due to its capacity to infect humans. Recently, some evidences have demonstrated that T. evansi infection causes severe genotoxic and cytotoxic damage in brain cells, contributing to the pathogenesis and clinical signs of the disease. In this sense, the aim of this study was to evaluate whether nerolidol-loaded in nanospheres, a natural compound with trypanocidal and neuroprotective effects, is able to protect the brain tissue from the cytotoxic and genotoxic effects found during T. evansi infections. Trypanosoma evansi induced brain genotoxic effects through increased damage index (DI) and frequency of damage (FD) when compared to the control group. Moreover, T. evansi induced cytotoxic effects through the reduction of brain cell viability compared to the control group. The metabolites of nitric oxide (NO x ) increased in infected animals compared to the control group. The treatment with nerolidol-loaded in nanospheres prevented the increase on brain DI, FD, and NO x levels, as well as the reduction on cell viability. Based on these evidences, these results confirm that T. evansi induces genotoxic and cytotoxic damage mediated by the upregulation of NO x levels. The most important finding is that nerolidol-loaded in nanospheres was able to prevent DNA damage and cell mortality through the modulation of brain NO x levels. In summary, this treatment can be considered an interesting approach to prevent T. evansi brain damage due its anti-inflammatory property.

Nucleotide and nucleoside involvement in immunomodulation in experimental Chagas disease.

The aim of this study was to evaluate whether Trypanosma cruzi infections cause alterations in the levels of seric purines, which could contribute to host immunomodulation. Twelve mice were divided into two groups identified as control (uninfected) and infected (T. cruzi) groups. The influence of the disease on seric purine levels was verified on day 20 post-infection (PI) by HPLC. Infected mice had circulating trypomastigotes during the experiment, as well as amastigote forms in the heart associated with inflammatory infiltrates. Increases on adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine (ADO), inosine (INO), and uric acid (URIC) levels were observed in the infected animals, while the adenosine monophosphate (AMP) and xanthine (XAN) levels were reduced compared with mice of the control group, indicating a possible impairment on the purinergic system, and consequently, on the immune system during the clinical course of the disease. In summary, the T. cruzi infection alters the seric purine levels, and consequently, modulates the immune system.

Ecto-enzymes activities in splenic lymphocytes of mice experimentally infected by Trypanosoma cruzi and treated with specific avian immunoglobulins: an attempt to improve the immune response.

The aim of this study was to evaluate the therapeutic efficacy of specific avian polyclonal antibodies (IgY) against Trypanosoma cruzi and their interaction with ecto-enzymes of the purinergic system (NTPDase and adenosine deaminase (ADA) activities) in splenic lymphocytes. For this, mice were divided into six groups: three non-infected (A, B, and C) and three infected (D, E, and F). The groups A and D were composed by negative and positive controls, respectively; while the groups B and E were treated prophylactically with IgY (50 mg/kg), and the groups C and F were treated therapeutically with IgY (50 mg/kg). Treatment with IgY reduced parasitemia on day 6 post-infection (PI) compared to the infected control group, but it was similar on day 8 PI. Moreover, infected and treated animals (the groups E and F) did not show neither amastigotes in the cardiac tissue nor cardiac lesions when compared to the positive control group (the group D). The E-NTPDase (ATP and ADP as substrate) and ADA activities in splenic lymphocytes increased significantly in the positive control group (the group D) compared to the negative control group (the group A). The therapeutic treatment of IgY (the group F) was able to prevent the increase of E-NTPDase and E-ADA activities compared to the positive control group (the group D), but this finding was not observed in animals that received the prophylactic treatment (the group E). The therapeutic treatment of IgY may be considered an interesting approach to improve the immune response of mice experimentally infected by T. cruzi.

Chagas disease: modulation of the inflammatory response by acetylcholinesterase in hematological cells and brain tissue.

Chagas disease is an acute or chronic illness that causes severe inflammatory response, and consequently, it may activate the inflammatory cholinergic pathway, which is regulated by cholinesterases, including the acetylcholinesterase. This enzyme is responsible for the regulation of acetylcholine levels, an anti-inflammatory molecule linked to the inflammatory response during parasitic diseases. Thus, the aim of this study was to investigate whether Trypanosoma cruzi infection can alter the activity of acetylcholinesterase and acetylcholine levels in mice, and whether these alterations are linked to the inflammatory cholinergic signaling pathway. Twenty-four mice were divided into two groups: uninfected (control group, n = 12) and infected by T. cruzi, Y strain (n = 12). The animals developed acute disease with a peak of parasitemia on day 7 post-infection (PI). Blood, lymphocytes, and brain were analyzed on days 6 and 12 post-infection. In the brain, acetylcholine and nitric oxide levels, myeloperoxidase activity, and histopathology were analyzed. In total blood and brain, acetylcholinesterase activity decreased at both times. On the other hand, acetylcholinesterase activity in lymphocytes increased on day 6 PI compared with the control group. Infection by T. cruzi increased acetylcholine and nitric oxide levels and histopathological damage in the brain of mice associated to increased myeloperoxidase activity. Therefore, an intense inflammatory response in mice with acute Chagas disease in the central nervous system caused an anti-inflammatory response by the activation of the cholinergic inflammatory pathway.

Treatment with 3'-deoxyadenosine and deoxycoformycin in mice infected by Trypanosoma cruzi and its side effect on purinergic enzymes.

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.

Treatment with tucumã oil (Astrocaryum vulgare) for diabetic mice prevents changes in seric enzymes of the purinergic system: Improvement of immune system.

The aim of this study was to evaluate the enzymatic activity of the purinergic system in sera samples from alloxan-induced diabetic mice treated with tucumã oil (Astrocaryum vulgare). For this, the mice were divided into four groups (n=6): control/water (the group CW); control/tucumã oil (the group CT); diabetic/water (the group DW), and diabetic/tucumã oil (the group DT) treated for 14days with 5.0mLkg-1 via oral gavage. On day 14 post-treatment, mice were submitted to euthanasia and blood samples were collected by cardiac puncture. Tucumã oil treatment significantly decreased (p<0.05) blood glucose levels in the group DT compared to the group DW. These results demonstrated an increase (p<0.05) in NTPDase (adenosine triphosphate (ATP substrate) or adenosine diphosphate (ADP substrate)), 5'-nucleotidase (AMP substrate) and adenosine deaminase (ADA; adenosine substrate) activities in serum from the group DW compared to the group CW. Tucumã oil treatment prevented these alterations in the group DT compared to the group DW, and restored these parameters near to the group CW. In summary, the treatment with tucumã oil was able to modulate the alterations caused by hyperglycemia probably by the presence of carotenoids compounds, maintaining normal levels of ATP, ADP, AMP and adenosine, molecules that could exhibit anti-inflammatory properties, depending on their concentration. Thus, the tucumã oil is a promising natural compound with protective action against diabetes and its side effects, such as changes in the purinergic system, improving the immune system.

Relation between acetylcholinesterase and Na+, K+-ATPase activities with impaired memory of mice experimentally infected by Trypanosoma cruzi.

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.

Trypanocidal action of Lippia alba and Lippia origanoides essential oils against Trypanosoma evansi in vitro and in vivo used mice as experimental model.

Parasitic diseases have an enormous health and economic impact and are a particular problem in tropical regions of the world. Disease caused by protozoa, such as trypanosomiasis, are the cause of most parasite related morbidity and mortality. Thus, the aim of this study was to verify the trypanocidal effectiveness of Lippia alba and Lippia origanoides against Trypanosoma evansi in vitro and in vivo. L. alba and L. origanoides were used in vitro on trypomastigotes at different concentrations (0.5, 1.0 and 2.0 %) and exposure times (0, 1, 3, 6 and 9 h). The three concentrations tested showed trypanocidal activity in vitro, completely eliminating the parasites in small concentration after 6 h of assay. In vivo tests were performed using mice as the experimental model. T. evansi infected mice were treated with L. alba and L. origanoides with dose of 1.5 mL kg-1 during 5 days. These protocols did not provide curative efficacy, however the mice treated with L. origanoides showed a significant increase in the longevity when compared to control group. Active compounds present in essential oils, such as L. origanoides, may potentiate the treatment of trypanosomosis when associated with other trypanocidal drugs.

Solving the challenge of the blood-brain barrier to treat infections caused by Trypanosoma evansi: evaluation of nerolidol-loaded nanospheres in mice.

Despite significant advances in therapies against Trypanosoma evansi, its effective elimination from the central nervous system (CNS) remains a difficult task. The incapacity of trypanocidal drugs to cross the blood-brain barrier (BBB) after systemic administrations makes the brain the main refuge area for T. evansi. Nanotechnology is showing great potential to improve drug efficacy, such as nerolidol-loaded nanospheres (N-NS). Thus, the aim of this study was to investigate whether the treatment with N-NS was able to cross the BBB and to eliminate T. evansi from the CNS. High-performance liquid chromatography revealed that N-NS can cross the BBB of T. evansi-infected mice, while free nerolidol (F-N) neither the trypanocidal drug diminazene aceturate (D.A.) were not detected in the brain tissue. Polymerase chain reaction revealed that 100% of the animals treated with N-NS were negatives for T. evansi in the brain tissue, while all infected animals treated with F-N or D.A. were positives. Thus, we concluded that nanotechnology improves the therapeutic efficacy of nerolidol, and enables the transport of its active principle through the BBB. In summary, N-NS treatment can eliminate the parasite from the CNS, and possesses potential to treat infected animals.

The use of tucumã oil (Astrocaryum vulgare) in alloxan-induced diabetic mice: effects on behavior, oxidant/antioxidant status, and enzymes involved in brain neurotransmission.

The aim of this study was to investigate the effects of tucumã oil (Astrocaryum vulgare) on memory, enzymatic activities of sodium-potassium pump (Na+, K+-ATPase) and acetylcholinesterase (AChE) in the brain of alloxan-induced diabetic mice. The animals were divided into four groups (n = 6 each): the group A (non-diabetic/water), the group B (non-diabetic/tucumã oil), the group C (diabetic/water), and the group D (diabetic/tucumã oil) treated 14 days with 5.0 mL kg-1 via oral gavage. Untreated diabetic mice (the group C) showed memory deficit, increased levels of thiobarbituric acid reactive species (TBARS) and protein carbonylation (PC), and decreased (p < 0.05) catalase (CAT), superoxide dismutase (SOD), and the Na+, K+-ATPase activities, while acetylcholinesterase (AChE) activity showed a significant increase (p < 0.05) compared to non-diabetic mice (the group A). Tucumã oil prevented these alterations in diabetic mice treated with tucumã oil (the group D) compared to diabetic mice (the group C). Our findings suggest that tucumã oil can modulate cholinergic neurotransmission resting membrane potential of neurons by modulating enzymatic antioxidant defenses. In conclusion, the present data showed that treatment with tucumã oil is beneficial to diabetic mice, demonstrating that this oil can modulate cholinergic neurotransmission and consequently improve or avoid memory deficits.

Enzymes that hydrolyze adenine nucleotides in a model of hypercholesterolemia induced by Triton WR-1339: protective effects of ß-caryophyllene.

Purinergic system has been proven to play a critical role in the inflammatory process and to represent an important therapeutic target to improve the immune response during hypercholesterolemia. ß-caryophyllene, a phytocannabinoid compound, has a powerful hypolipidemic and anti-inflammatory actions. However, the effects of ß-caryophyllene on seric enzymes of purinergic system have not been evaluated. The purpose of this study was to investigate whether ß-caryophyllene is able to ameliorate the seric activities of NTPDase and adenosine deaminase (ADA) in a model of hypercholesterolemia induced by Triton WR-1339. The activities of NTPDase and ADA were evaluated enzymatically, and the seric levels of ß-caryophyllene were evaluated by high-performance liquid chromatography. We found that treatment with ß-caryophyllene ameliorates the enzymatic activities of NTPDase and ADA in serum of hypercholesterolemic rats, in a concentration-dependent manner. These results indicated that ß-caryophyllene treatment could improve the immune response during hypercholesterolemia through purinergic pathway.