RESUMO
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.
Assuntos
Interações Hospedeiro-Patógeno , Células-Tronco Neurais/patologia , Células-Tronco Neurais/parasitologia , Trypanosoma/crescimento & desenvolvimento , Animais , Diferenciação Celular , CamundongosRESUMO
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.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Resveratrol/farmacologia , Células-Tronco/efeitos dos fármacos , Animais , Doença de Chagas/tratamento farmacológico , Modelos Animais de Doenças , Feminino , Camundongos , Neurogênese/efeitos dos fármacos , Neurônios/citologia , Células-Tronco/metabolismo , Trypanosoma cruziRESUMO
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
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.
Assuntos
Dípteros , Moscas Domésticas , Inseticidas , Lamiaceae , Lamiales , Lavandula , Muscidae , Óleos Voláteis , AnimaisRESUMO
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.
Assuntos
Encéfalo/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Sesquiterpenos/uso terapêutico , Tripanossomíase/tratamento farmacológico , Animais , Encéfalo/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Feminino , Camundongos , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico/metabolismo , Sesquiterpenos/farmacologia , Tripanossomíase/metabolismoRESUMO
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.
Assuntos
Cardiomiopatia Chagásica/imunologia , Imunomodulação , Nucleosídeos de Purina/imunologia , Nucleotídeos de Purina/imunologia , Trypanosoma cruzi/imunologia , Animais , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/patologia , Modelos Animais de Doenças , Feminino , CamundongosRESUMO
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.
Assuntos
Adenosina Desaminase , Anticorpos Antiprotozoários/farmacologia , Proteínas Aviárias/farmacologia , Doença de Chagas , Imunoglobulinas/farmacologia , Proteínas de Protozoários , Baço , Trypanosoma cruzi , Adenosina Desaminase/imunologia , Adenosina Desaminase/metabolismo , Animais , Doença de Chagas/tratamento farmacológico , Doença de Chagas/enzimologia , Doença de Chagas/imunologia , Galinhas , Feminino , Linfócitos/enzimologia , Linfócitos/imunologia , Linfócitos/patologia , Camundongos , Proteínas de Protozoários/imunologia , Proteínas de Protozoários/metabolismo , Baço/enzimologia , Baço/imunologia , Baço/parasitologia , Baço/fisiologia , Trypanosoma cruzi/enzimologia , Trypanosoma cruzi/imunologiaRESUMO
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.
Assuntos
Acetilcolina/sangue , Acetilcolinesterase/sangue , Encéfalo/metabolismo , Cardiomiopatia Chagásica/sangue , Linfócitos/metabolismo , Trypanosoma cruzi , Animais , Encéfalo/patologia , Cardiomiopatia Chagásica/patologia , Linfócitos/patologia , Camundongos , Óxido Nítrico/sangue , Peroxidase/sangueRESUMO
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
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.
Assuntos
Acetilcolinesterase/metabolismo , Infecções Protozoárias do Sistema Nervoso Central/enzimologia , Córtex Cerebral/enzimologia , Transtornos da Memória/enzimologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Trypanosoma cruzi/patogenicidade , Animais , Comportamento Animal , Encéfalo/enzimologia , Encéfalo/parasitologia , Encéfalo/patologia , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Infecções Protozoárias do Sistema Nervoso Central/patologia , Infecções Protozoárias do Sistema Nervoso Central/psicologia , Córtex Cerebral/parasitologia , Córtex Cerebral/patologia , Doença de Chagas , Modelos Animais de Doenças , Feminino , Gliose/enzimologia , Gliose/parasitologia , Gliose/patologia , Coração , Humanos , Transtornos da Memória/parasitologia , Transtornos da Memória/patologia , Transtornos da Memória/psicologia , Camundongos , Tripanossomíase/parasitologia , Tripanossomíase/psicologiaRESUMO
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.
Assuntos
Antioxidantes/metabolismo , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Diabetes Mellitus Experimental , Magnoliopsida/química , Oxidantes/sangue , Óleos de Plantas/farmacologia , Transmissão Sináptica/efeitos dos fármacos , Animais , Encéfalo/patologia , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Feminino , Camundongos , Óleos de Plantas/químicaRESUMO
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.
Assuntos
Barreira Hematoencefálica , Nanosferas , Sesquiterpenos/administração & dosagem , Tripanossomicidas/administração & dosagem , Tripanossomíase/tratamento farmacológico , Animais , Encéfalo/efeitos dos fármacos , Camundongos , Nanotecnologia/métodos , Sesquiterpenos/química , Sesquiterpenos/uso terapêutico , Tripanossomicidas/química , Tripanossomicidas/uso terapêutico , Trypanosoma/efeitos dos fármacos , Tripanossomíase/parasitologiaRESUMO
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.
Assuntos
Nucleotídeos de Adenina/metabolismo , Adenosina Desaminase/metabolismo , Hipercolesterolemia/metabolismo , Polietilenoglicóis/farmacologia , Pirofosfatases/metabolismo , Sesquiterpenos/farmacologia , Animais , Colesterol/sangue , Cromatografia Líquida de Alta Pressão , Feminino , Hidrólise , Hipercolesterolemia/induzido quimicamente , Hipercolesterolemia/prevenção & controle , Sesquiterpenos Policíclicos , Ratos , Ratos WistarRESUMO
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
Oxidative stress has been considered as a pathological mechanism that contributes to initiation and progression of cardiac injury during the Trypanosoma evansi infection. In this sense, the natural compounds with antioxidant and free radical scavenger abilities, such the Achyrocline satureioides essential oil loaded in nanocapsules (AS-NC), may be considered important approach to minimize the cardiac damage. Thus, the aim of this study was to investigate whether AS-NC treatment is able to prevents or reduce the cardiac oxidative damage in infected rats with T. evansi. Heart samples from rats infected by T. evansi showed increased reactive oxygen species (ROS), thiobarbituric reactive-acid substances (TBARS) and glutathione reduced (GSH) levels, while catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities decreased compared with uninfected and untreated animals. Also, the seric biomarkers of cardiac function increased in the infected animals compared with uninfected animals. AS-NC treatment reduced ROS and TBARS levels, ameliorate cardiac CAT and SOD activities of infected rats, and reduced seric biomarkers of cardiac function. AS-NC treatment protected the heart from oxidative stress caused by T. evansi, which might be due to its antioxidant properties. AS-NC might be considered a promising therapeutic agent against oxidative stress, when associated with nanotechnology.
Assuntos
Achyrocline/química , Antioxidantes/farmacologia , Miocárdio/patologia , Nanocápsulas/administração & dosagem , Óleos Voláteis/farmacologia , Tripanossomíase/tratamento farmacológico , Animais , Antioxidantes/administração & dosagem , Catalase/análise , Feminino , Óleos Voláteis/administração & dosagem , Oxidantes , Ratos Wistar , Superóxido Dismutase/análise , Resultado do TratamentoRESUMO
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 evaluate the effect of ß-caryophyllene on hypercholesterolemia using a model of hyperlipidemia induced by Triton WR-1339 in rats, as well as its possible effect on hepatic antioxidant enzymes. Thus, total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were measured in serum, while reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), hepatic 3-hydroxy-3-methylglutayl coenzyme A (HMG-CoA) reductase, superoxide dismutase (SOD), and catalase (CAT) activities were measured in the hepatic tissue. In addition, seric concentrations of ß-caryophyllene were measured to perform correlation studies. Serum samples from hypercholesterolemic rats show higher (p < 0.05) levels of total cholesterol, triglycerides, and LDL cholesterol, and lower (p < 0.05) levels of HDL cholesterol compared to non-hypercholesterolemic rats. ß-Caryophyllene treatment reduced (p < 0.05) the levels of total cholesterol, triglycerides and LDL cholesterol, similar to the reference drug simvastatin. However, HDL cholesterol levels did not increase with the treatment. ß-Caryophyllene treatment was able to inhibit the HMG-CoA reductase activity, as well as to prevent the increase on ROS and TBARS levels, and ameliorate the antioxidant system. In summary, our findings demonstrated that ß-caryophyllene has hypolipidemic effect via inhibition of the hepatic HMG-CoA reductase, like the standard drug simvastatin, and this inhibition suggests a possible mechanism of hypolipidemic action. Thus, our results indicate that ß-caryophyllene can be used to treat dyslipidemic diseases because it exerts a similar effect as the reference drug, protecting the liver against lipid damage and improving the hepatic antioxidant defense system.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipercolesterolemia/tratamento farmacológico , Lipídeos/sangue , Fígado/efeitos dos fármacos , Sesquiterpenos/farmacologia , Animais , Antioxidantes/farmacologia , Biomarcadores/sangue , Catalase/metabolismo , Modelos Animais de Doenças , Feminino , Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/sangue , Hipercolesterolemia/sangue , Hipercolesterolemia/induzido quimicamente , Fígado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Sesquiterpenos Policíclicos , Polietilenoglicóis , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/sangue , Sinvastatina/farmacologia , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
The aim of this study was to evaluate whether the treatment with Achyrocline satureioides essential oil-loaded in nanocapsules (AS-NC) is able to protect the hepatic tissue against cytotoxic damage caused by Trypanosoma evansi. Thus, the rats were divided into four groups (n = 6 per group): uninfected/saline, uninfected/AS-NC, infected/saline, and infected/AS-NC. At day 4 post-infection (PI), the animals were euthanized and liver and sera samples were collected to perform the hepatic cell viability assay, and to determine seric levels of reactive oxygen species (ROS) and nitric oxide metabolites (NOx). Cell viability decreased (p < 0.05) in the infected/saline group compared to uninfected/saline group, while the treatment with AS-NC avoided this alteration in infected rats. Seric ROS and NOx levels increased (p < 0.05) in the infected/saline group compared to uninfected/saline group, while the treatment with AS-NC avoided this effect on ROS levels of infected rats. In summary, the treatment with AS-NC was able to protect the liver tissue against the cytotoxic effect caused by the parasite by avoiding exacerbated production of ROS.
Assuntos
Achyrocline/química , Fígado/patologia , Fígado/parasitologia , Nanocápsulas/administração & dosagem , Óleos Voláteis/administração & dosagem , Trypanosoma/efeitos dos fármacos , Tripanossomíase/patologia , Tripanossomíase/parasitologia , Animais , Feminino , Fígado/efeitos dos fármacos , Nanocápsulas/química , Nanocápsulas/toxicidade , Nanocápsulas/ultraestrutura , Óxido Nítrico/metabolismo , Óleos Voláteis/química , Óleos Voláteis/toxicidade , Extratos Vegetais/química , Ratos , Espécies Reativas de Oxigênio/metabolismo , Tripanossomíase/tratamento farmacológico , Tripanossomíase/metabolismoRESUMO
The aim of this study was to evaluate the effect of nerolidol free (N-F) and nerolidol-loaded in nanospheres (N-NS) on the hepatic antioxidant/oxidant status of mice experimentally infected by Trypanosoma evansi. In the liver it was measured: reactive oxygen species (ROS), thiobarbituric reactive acid substances (TBARS) and non-protein thiols (NPSH), catalase (CAT), superoxide dismutase (SOD) and glutathione-S-transferase (GST) and performed histopathological examination. In addition, seric levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. Liver samples from mice infected by T. evansi showed increased (P < 0·05) ROS, TBARS, AST and ALT levels and SOD activity, and decreased NPSH levels and CAT activity (P < 0·05) compared with uninfected animals. N-NS treatment prevented (P < 0·05) ROS and TBARS increase, and increased NPSH levels, and ameliorate CAT and SOD activities on liver of infected mice. Moreover, N-NS treatment reduced (P < 0·05) AST and ALT levels, and prevented histopathological changes caused by the parasite. N-NS protected the liver from the oxidative stress caused by T. evansi, which might be due to its antioxidant properties. Nerolidol might be considered a promising therapeutic agent against oxidative stress, and nanotechnology is an encouraging approach to be explored.
Assuntos
Fígado/patologia , Nanosferas/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Sesquiterpenos/uso terapêutico , Tripanossomicidas/uso terapêutico , Trypanosoma/classificação , Tripanossomíase/tratamento farmacológico , Animais , Feminino , Fígado/parasitologia , Camundongos , Sesquiterpenos/administração & dosagem , Tripanossomicidas/administração & dosagemRESUMO
The aim of this study was to investigate the effect of nerolidol-loaded nanospheres (N-NS) on the treatment of memory impairment caused by Trypanosoma evansi in mice, as well as oxidative stress, and Na+, K+-ATPase and acetylcholinesterase (AChE) activities in brain tissue. Animals were submitted to behavioral tasks (inhibitory avoidance task and open-field test) 4 days postinfection (PI). Reactive oxygen species (ROS) and thiobarbituric acid-reactive substance (TBARS) levels and catalase (CAT), superoxide dismutase (SOD), Na+, K+-ATPase and AChE activities were measured on the fifth-day PI. T. evansi-infected mice showed memory deficit, increased ROS and TBARS levels and SOD and AChE activities, and decreased CAT and Na+, K+-ATPase activities compared to uninfected mice. N-NS prevented memory impairment and oxidative stress parameters (except SOD activity), while free nerolidol (N-F) restored only CAT activity. Also, N-NS treatment was able to prevent alterations in Na+, K+-ATPase and AChE activities caused by T. evansi infection. A significantly negative correlation was observed between memory and ROS production (p < 0.001; r = -0.941), as well as between memory and AChE activity (p < 0.05; r = -0.774). On the contrary, a significantly positive correlation between memory and Na+, K+-ATPase activity was observed (p < 0.01; r = 0.844). In conclusion, N-NS was able to reverse memory impairment and to prevent increased ROS and TBARS levels due to amelioration of Na+, K+-ATPase and AChE activities and to activation of the antioxidant enzymes, respectively. These results suggest that N-NS treatment may be a useful strategy to treat memory dysfunction and oxidative stress caused by T. evansi infection.