N-acetyl-cysteine inhibits liver oxidative stress markers in BALB/c mice infected with Leishmania amazonensis

BACKGROUND Leishmaniasis is a parasitosis caused by several species of the genus Leishmania. These parasites present high resistance against oxidative stress generated by inflammatory cells. OBJECTIVES To investigate oxidative stress and molecular inflammatory markers in BALB/c mice infected with L. amazonensis and the effect of antioxidant treatment on these parameters. METHODS Four months after infection, oxidative and inflammatory parameters of liver, kidneys, spleen, heart and lungs from BALB/c mice were assessed. FINDINGS In liver, L. amazonensis caused thiol oxidation and nitrotyrosine formation; SOD activity and SOD2 protein content were increased while SOD1 protein content decreased. The content of the cytokines IL-1β, IL-6, TNF-α, and the receptor of advanced glycation endproducts (RAGE) increased in liver. Treatment with the antioxidant N-acetyl-cysteine (20 mg/kg b.w) for five days inhibited oxidative stress parameters. MAIN CONCLUSIONS L. amazonensis induces significant alterations in the redox status of liver but not in other organs. Acute antioxidant treatment alleviates oxidative stress in liver, but it had no effect on pro-inflammatory markers. These results indicate that the pathobiology of leishmaniasis is not restricted to the cutaneous manifestations and open perspectives for the development of new therapeutic approaches to the disease, especially for liver function.

Avaliação da capacidade leishmanicida de espécies vegetais do cerrado / Evaluation of the leishmanicidal activity of plant species of the Brazilian savanna

Para identificar as propriedades químicas de plantas do Cerrado, realizou-se um levantamentoetnobotânico que resultou na seleção de sete espécies vegetais de acordo com as indicações terapêuticaspara antibiótico, anti-inflamatório, analgésico, antiofídico e cicatrizante. Foram testados os extratoshidroalcoólicos das seguintes plantas quanto à sua atividade contra as formas promastigotas de Leishmaniaamazonensis: Terminalia fagifolia Mart. (Combretaceae), Vellozia squamata Pohl. (Velloziaceae),Vochysia haenkeana (Spreng.) Mart. (Vochysyaceae), Siparuna guianensis Aublet (Siparunaceae),Lafoensia pacari St. Hil. (Lythraceae), Galactia glauscecens Kunth. (Leguminosae) e Plathymeniareticulata Benth. (Mimosaceae). Feita a triagem para identificação da atividade leishmanicida,calculou-se a concentração inibitória do crescimento (IC50) em relação às culturas não tratadas com osextratos. Nas espécies L. pacari, G. glaucensces e P. reticulata, seus extratos demonstraram IC50 comvalores de 14,6 mug/mL, 46,0 mug/mL e 59,5 mug/mL, respectivamente, apresentando maior eficácia eminduzir a morte dos parasitos. T. fagifolia, V. squamata e V. haenkeana apresentaram IC50 com valoresde 446,1 mug/mL, 305,0 mug/mL e 85,1 mug/mL, respectivamente, demonstrando eficácia moderada.A prospecção fitoquímica evidenciou a presença de flavonoides, triterpenoides, esteroides e taninosque, segundo a literatura, são responsáveis pela atividade leishmanicida. Esses resultados indicam anecessidade de mais estudos para a avaliação da atividade em infecções in vivo e do fracionamento dassubstâncias em busca dos princípios ativos responsáveis pela ação leishmanicida...

In order to identify chemical properties of plants of the Brazilian savanna (Cerrado) an ethnobotanicalsurvey was performed. Seven plant species were selected according to their indications for antibiotic,anti-inflammatory, analgesic, anti-ophidian and healing properties. The following hydroalcoholic extracts of these plants were tested for activity against promastigotes of Leishmania amazonensis:Terminalia fagifolia Mart. (Combretaceae), Vellozia squamata Pohl. (Velloziaceae), Vochysiahaenkeana (Spreng.) Mart. (Vochysyaceae), Siparuna guianensis Aublet (Siparunaceae), Lafoensiapacari St. Hil. (Lythraceae), Galactia glauscecens Kunth. (Leguminosae) and Plathymeniareticulata Benth. (Mimosaceae). The growth inhibitory concentration (IC50) of these extracts wascalculated in relation to untreated cultures. Higher efficacy in inducing the death of parasites wasdemonstrated with extracts of L. pacari, G. glaucensces and P. reticulata, which showed IC50 valuesof 14.6 mg/mL, 46.0 mg/mL and 59.5 mg/mL, respectively. Moderate effectiveness was shown withT. fagifolia, V. squamata and V. haenkeana extracts, with values of 446.1, mg/mL 305.0 mg/mL and85.1 mg/mL respectively. Phytochemical studies showed the presence of flavonoids, triterpenoids,steroids and tannins that, according to the literature, are responsible for the leishmanicidal activity.These results indicate the need for future studies to evaluate the activity of these extracts againstinfections in vivo, as well as the fractionation of substances, in search of the active componentsresponsible for the leishmanicidal action...

The concurrent occurrence of Leishmania chagasi infection and childhood acute leukemia in Brazil

Objective: This study investigated the co-existence of Leishmania chagasi infection and childhood leukemia in patients naïve to treatment; this has serious clinical and epidemiological implications. Methods: The seroprevalence of L. chagasi antibodies prior to any treatment was investigated in children with clinical features of acute leukemia. Serological tests were performed in 470 samples drawn from under 14-year-old children from different regions of Brazil with clinical suspicion of acute leukemia. Acute leukemia subtypes were characterized by immunophenotyping using flow cytometry. Morphological analyses of bone marrow aspirates were systematically performed to visualize blast cells and/or the formation of L. chagasi amastigotes. Data analysis used a standard univariate procedure and the Pearson's chi-square test. Results: The plasma of 437 children (93%) displayed antibodies against L. chagasi by indirect immunofluorescence assay and enzyme-linked immunosorbent assay tests. Of the 437 patients diagnosed from 2002 to 2006, 254 had acute lymphoblastic leukemia, 92 had acute myeloid leukemia, and 91 did not have acute leukemia. The seroprevalence of L. chagasi antibodies according to the indirect immunofluorescence assay test (22.5%) was similar in children with or without acute leukemia (p-value = 0.76). The co-existence of visceral leishmanasis and acute leukemia was confirmed in 24 children. The overall survival of these children was poor with a high death rate during the first year of leukemia treatment. Conclusion: In the differential diagnosis of childhood leukemia, visceral leishmanasis should be considered as a potential concurrent disease in regions where L. chagasi is endemic...

Fatores relacionados com a positividade de cães para leishmaniose visceral em área endêmica do Estado do Rio Grande do Norte, Brasil / Factors related to positive testing of dogs for visceral leishmaniasis in endemic area in the state of Rio Grande do Norte, Brazil

O presente estudo objetivou descrever alguns fatores relacionados à positividade de cães para leishmaniose visceral, em área endêmica do Estado do Rio Grande do Norte. Foram analisados 198 cães, dos quais 62 foram recrutados de propriedades rurais e 136 de residências urbanas. O diagnóstico foi realizado através dos testes de imunofluorescência indireta e imunoadsorção enzimática. Dos cães analisados, 45 por cento dos positivos eram provenientes da área rural e 35 por cento da área urbana. Analisando a função dos animais, a prevalência foi de 50 por cento dos cães de guarda nas áreas rural e de 43 por cento na área urbana. Quanto aos cães que tinham contato com outros cães de origem rural ou urbana, a prevalência observada de foi 54 por cento e 32 por cento, respectivamente. No que se refere ao sexo, as fêmeas da zona rural foram mais prevalentes. Estes resultados sugerem uma atenção maior sobre o papel destes animais como reservatório dessa zoonose, como também na urbanização da leishmaniose visceral e o inquérito epidemiológico desta doença, no qual estas informações poderão contribuir para o planejamento de estratégias de controle do cão como reservatório doméstico.

This study aimed at describing several factors related to positive testing of dogs for visceral leishmaniasis, in an endemic area of the state of Rio Grande do Norte. Sera of 198 dogs were analyzed, 62 from rural properties and 136 from urban residences. Diagnosis was performed through indirect immunofluorescence and enzyme-linked immunosorbent assay. Forty five percent of positive dogs were from the rural area and 35 percent came from the urban area. Concerning the analysis of dogs' function, the watchdogs showed greater prevalence, with 50 percent prevalence in the rural area and 43 percent in the urban area. With regard to contact with other dogs and origin in rural or urban areas, the prevalence was 54 percent and 32 percent respectively. In relation to gender, females from the rural area were more prevalent. These results suggest more attention should be paid to dogs as reservoirs for this zoonosis, as well as their important role in the urbanization of Leishmaniasis and in epidemiological survey of the disease. These data can contribute to the planning of strategies for control, targeting dogs as domestic reservoirs.

The colonization of cartilage by "Trypanosoma cruzi" associated with inflammatory reaction

Objetivo: Avaliar no modelo murino o nível de colonizaçao de cartilagens costais e articulares, assim como os ligamentos pelo Trypanosoma cruzi. Métodos: Estudo histopatológico e histoquímico das cartilagens, ligamentos e musculatura esquelética em camundongos atímicos e eutímicos na fase aguda da doença de Chagas experimental. Resultados: Foi observado que em camundongos jovens, infectados com duas amostras polares de T. cruzi, as cartilagens, os ligamentos, a musculatura esquelética e a medula óssea apresentavam-se altamente colonizados pelo parasito. A colonizaçao do pericôndrio e ligamentos muitas vezes está associada com uma reaçao inflamatória em que predomina um infiltrado mononuclear. A idade é um fator importante na colonizaçao da cartilagem pelo parasito, sendo rara em camundongos adultos. A miosite observada no miocárdio e músculos esqueléticos de camundongos, que apresentam a resposta T-dependente intacta, muitas vezes mostra uma paralisia de membros posteriores. Neste caso, observamos certa freqüência de calcificaçao da fibra muscular demonstrada por testes histoquímicos. Camundongos atímicos (Nude) nao têm miosite nem calcificaçao, porém apresentam carga parasitária em níveis extraordinários na musculatura lisa e estriada. Conclusoes: Os fenômenos de paralisia na fase aguda aparecem com freqüência associados com calcificaçoes observadas na musculatura esquelética e a uma intensa miosite. Os resultados mostraram que estes aspectos da patologia da doença de Chagas experimental estao relacionados com a resposta T-dependente, pois camundongos atímicos nunca apresentaram o quadro acima descrito, apesar da intensa carga parasitária nos tecidos musculares. Cepas polares, quer sejam miotrópica ou reticulotrópicas, estao envolvidas com os fenômenos de paralisia. Os condrócitos sao colonizados pelo T. cruzi, assim como o pericôndrio, o que desencadeia um processo inflamatório local

Enhancement of Leishmania amazonensis infection in BCG non-responder mice by BCG-antigen specific vaccine

Different patterns of cutaneous leishmaniasis can be induced when a challenge of alike dose of Leishmania amazonensis amastigotes in various inbred strains was applied. Two strains of mice, the Balb/c and C57 BL/10J, showed exceptional suscepbility, and 10(elevado a sexta potência) amastigotes infective dose lead, to ulcerative progressive lesions with cutaneous metastasis and loss by necrosis of leg on wich the footpad primary lesion occured. Lesions were also progressive but in a lower degree when C3H/HeN and C57BL/6 were infected. Lesions progress slowly in DBA/2 mice presenting lesions wich reach a discreet peack after 12 weeks, do not heal but do not uncerate. DBA/2 mice is, therefore, a good model for immunomodualtion. In attempt to determine the influence of BCG in vaccination schedule using microsomal fraction, DBA/2 became an excellent model, since it is also a non-responder to BCG. Vaccination of DBA/2 mice, receiving the same 10(elevado a sexta potência) BCG viable dose and 10 *g or 50 *g of protein content of microsomal fraction, lead to a progressive disease with time course similar to those observed in susceptible non-vaccinated C57BL/10J mice after 6 months of observation. An enhancement of infection in BCG non-responder mice suggests that use of BCG as immunostimulant in humans could be critical for both vaccination and immunoprophylactic strategies

Schizotrypanids: the occurence of dermatitis in immunodeficiency animals infected with Trypanosoma cruzi

Congenitally athymic nude Balb/c (nu/nu) and their phenothypically normal adult and neonate littermates (nu/+), the C3H/HeN as well, were intraperitoneally infected with two strains (Y or CL) of Trypanossoma cruzi. The nude mice and the neonates developed a severe parasitaemia, the susceptible C3H/HeN also presented high level and adult Balb/c mice presented parasitaemia similar to that observed in outbred mice. Erythematous skin lesions were observed initially in infected athymic nude and neonates, being charactherized by nests of amastigotes in the dermis; in C3H/HeN infected mice no nest of parasite was observed but a low-grade inflammatory reaction was seen. In adult Balb/c or OF1 outbred mice nest was found but discreet inflammatory reaction was observed in severe infections

Trypanosoma cruzi: histopathology and time course infection in indomethacin - treated mice

A indometacina administrada por via oral ou intraperitoneal, na dose de 5mg/kg diariamente, durante infecçäo experimental em camundongos por Trypanosoma cruzi, provocou o aparecimento de reaçöes adversas similares àquelas observadas através do emprego de outros antiinflamatórios, tais como os corticosteróides. A parasitemia observada nos camundongos pertencentes ao grupo dos tratados pela indometacina foi significativamente mais elevada que nos grupos-controle. A taxa de mortalidade correlacionou-se aos níveis de parasitemia. Foram observados em quase todos os tecidos dos camundongos pertencentes ao grupo dos tratados com indometacina e infectados pelo T. cruzi cepa Y, do que nos grupos-controle normais. Näo foi observada infiltraçäo celular em camundongos tratados pela indometacina (tecidos infectados) enquanto um infiltrado duro de células mononucleares foi observado nos grupos-controle. As implicaçöes clínicas em pacientes chagásicos säo discutidas