RESUMO

In this study, the molluscicidal and antiparasitic activities of divaricatic acid was evaluated, targeting the mollusc Biomphalaria glabrata and cercariae of the helminth Schistosoma mansoni. Divaricatic acid showed high toxicity against both adult snails (5.5 µg/mL) and embryos (20 µg/mL after 6 h of exposure). Similar activity was observed in S. mansoni cercariae after only a short exposure time. The divaricatic acid proved to be a promising substance for the control of the snail B. glabrata, an intermediate host of schistosomiasis, as well as the cercariae of the pathogen.

RESUMO

PURPOSE: Some phytochemicals have shown the potential of being radiomodifiers, especially phenolic compounds, such as lichenic secondary metabolites. To evaluate the phytochemical usnic acid as a radiomodifier, embryonic cells of molluscs have been used due to their ease of collection, high sensitivity to physical and chemical agents, well-known embryology and low cost for analysis. MATERIALS AND METHODS: This study aimed to assess the radiosensitizing action of usnic acid on Biomphalaria glabrata embryos. Samples were irradiated with 4 Gy of gamma rays from a 60Co source (dose rate 2.906 Gy/h). An acute toxicity test was performed using B. glabrata embryos in the blastula stage, in order to determine the toxicity of usnic acid and to establish the lethal Concentration for 50% (LC50). Subsequently, the radiomodifing capacity of usnic acid was estimated using assays with B. glabrata embryos. RESULTS: Irradiation increased the number of non-viable embryos compared to unirradiated controls. Additionally, it was observed that embryos exposed to a non-toxic concentration of usnic acid (0.6 µg/mL) before irradiation showed a further enhancement in non-viable embryos when compared with exposure to ionizing radiation alone. CONCLUSION: The results presented here indicate that usnic acid makes cells more sensitive to the damaging effects of radiation.

Assuntos

Benzofuranos/farmacologia , Biomphalaria/embriologia , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/efeitos da radiação , Radiossensibilizantes/farmacologia , Animais , Benzofuranos/toxicidade , Radioisótopos de Cobalto , Raios gama , Dose Letal Mediana , Radiossensibilizantes/toxicidade

RESUMO

In this study, the molluscicidal and antiparasitic activities of divaricatic acid was evaluated, targeting the mollusc Biomphalaria glabrata and cercariae of the helminth Schistosoma mansoni. In addition, the environmental toxicity of divaricatic acid was assessed by bioassay using the microcrustacean Artemia salina. Divaricatic acid showed high toxicity against both adult snails (5µg/mL) and embryos (20µg/mL after 6h of exposure). Similar activity was observed in Schistosoma mansoni cercariae after only a short exposure time (10µg/mL after 30min of exposure). The divaricatic acid did not show toxicity in the acute test using Artemia salina at concentrations equal to or below 200µg/mL. The divaricatic acid proved to be a promising substance for the elimination of the snail Biomphalaria glabrata, an intermediate host of schistosomiasis, as well as the cercariae of the pathogen, while being non-toxic to the Artemia salina at the same concentrations. This is the first experimental observation of the molluscicidal and cercaricide activity of divaricatic acid.

Assuntos

Antiparasitários/farmacologia , Biomphalaria/efeitos dos fármacos , Depsídeos/farmacologia , Moluscocidas/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Animais , Artemia , Cercárias/efeitos dos fármacos

RESUMO

Studies about toxicological potential of usnic acid are limited. This way, the vast majority of data available in the literature are related only to biological activities. This is the first study that aimed to evaluate the oral toxicity of usnic acid during the period of organogenesis. Females rats were distributed in the control groups, treated I and II, at doses of 15 and 25 mg/kg, administered by gavage during the 6° to 15° days of pregnancy. After 20 days the fetuses were removed and analyzed. A reduction in weight gain during pregnancy, increased resorption, reduction in the number of viable fetuses, and their body weight were observed. Morphological changes in the litter were visualized as exposure of the eye and atrophy of the limbs at the dose of 25 mg/kg. Histological analysis of the liver of the fetus showed reduction in the number of megakaryocytes between experimental groups and increase in the number of hepatocytes in a dose of 25 mg/kg. The experimental model used in this study reveals teratogenic effect of usnic acid in the period of organogenesis. Since this achievement, the importance of evaluating the toxic effects of natural substances is imperative, in order to elucidate the care in their indication as drug.

Assuntos

Benzofuranos/administração & dosagem , Organogênese/efeitos dos fármacos , Teratogênese/efeitos dos fármacos , Animais , Ascomicetos/química , Benzofuranos/química , Peso Corporal/efeitos dos fármacos , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Feto/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Ratos

RESUMO

Responses to germination and initial growth of Lactuca sativa (lettuce) submitted to organic extracts and purified compounds of Cladonia verticillaris ("salambaia") were analyzed in this work. The experiments were conducted in laboratory conditions using extracts and pure compounds at different concentrations. None of the assays showed any influence on the germination of L. sativa seeds using C. verticillaris extracts; however, modifications in leaf area and seedling hypocotyl and root development occurred. In the growth experiments, seedlings exposed to ether or acetone extract showed diminished hypocotyl growth in detriment to the root stimulus, compared to controls. Increases in extract concentrations led to the formation of abnormal seedlings. To determine the allelochemicals of C. verticillaris, its principal components, fumarprotocetraric and protocetraric acids, were isolated and then analyzed by high performance liquid chromatography (HPLC). When the seedlings were exposed to the two acids separately, presented increased leaf area at all concentrations. In contrast, hypocotyl and root stimulus was observed only in the presence of protocetraric acid at different concentrations. Fumarprotocetraric as well as protocetraric acids, isolated and purified from C. verticillaris and Parmotrema dilatatum respectively, influenced the development of L. sativa seedlings at high concentrations, indicating a possible bioherbicide potential of these acids.

Assuntos

Agentes de Controle Biológico , Misturas Complexas/farmacologia , Germinação/efeitos dos fármacos , Lactuca/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Saccharomycetales/química , Sementes/efeitos dos fármacos , Lactuca/crescimento & desenvolvimento

RESUMO

The antidiabetic effect of Parkinsonia aculeata water soluble fraction (WSF) made of aerial parts of the plant (leaves and flowers) was investigated in alloxan diabetic rats. Its effect was compared with that of insulin (positive control). The physico-metabolic parameters measured were: body weight, food and liquid intake, urinary volume, hepatic glycogen, serum glucose, total cholesterol, HDL-cholesterol, triglycerides, urinary glucose and urea, and the weight of epididymal adipose tissue, liver, kidneys and the skeletal muscles (soleus and extensor digitorum longus). Oral administration of WSF (125 or 250 mg/kg) for 16 days exhibited a significant reduction in serum and urinary glucose, urinary urea, total cholesterol, HDL-cholesterol and triglycerides in alloxan diabetic rats. An improvement of hepatic glycogen, a decrease of liquid and food intake, and a significantly positive actions in the weight of skeletal muscles (soleus and extensor digitorum longus) and kidneys were also observed, but just diabetic group treated with WSF at a dose of 125 mg/kg showed significant reduction in urinary volume, body weight, an improvement of epididymal adipose tissue and a positive action in liver weight. The effects of WSF on the physico-metabolic parameters was comparable to those observed in diabetic insulin treated group. The results of this work suggest that P. aculeate may have new clinical significant choice in diabetes mellitus illness, and could explain the basis for its traditional use to manage diabetes-related complications by rural community of northeast of Brazil.

Assuntos

Diabetes Mellitus Experimental/tratamento farmacológico , Fabaceae/química , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Brasil , Relação Dose-Resposta a Droga , Ingestão de Alimentos/efeitos dos fármacos , Glucose/metabolismo , Hipoglicemiantes/administração & dosagem , Insulina/farmacologia , Lipídeos/sangue , Glicogênio Hepático/metabolismo , Masculino , Medicina Tradicional , Músculo Esquelético/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Componentes Aéreos da Planta , Extratos Vegetais/administração & dosagem , Ratos , Ratos Wistar , Ureia/urina

RESUMO

Chemotherapy for Chagas' disease is still unsatisfactory due to toxicity and limited effectiveness of the available drugs. In this work we have investigated the effect of usnic acid, isolated from lichen Cladonia substellata, against Trypanosoma cruzi, in vitro. Incubation of culture epimastigotes with 5-30microg/ml of this compound resulted in growth inhibition in a dosis-dependent manner. Ultrastructural analysis of treated epimastigotes showed damage to mitochondria, with a marked increase in kinetoplast volume and vacuolation of the mitochondrial matrix. Intense lysis of bloodstream trypomastigotes was observed with all drug concentrations tested. Besides mitochondrial and kinetoplast damage, trypomastigotes also presented enlargement of the flagellar pocket, as well as intense cytoplasm vacuolation. Treatment of infected macrophages with 40 or 80microg/ml usnic acid induced marked cytoplasm vacuolation in intracellular amastigote forms, with disorganization of parasite kinetoplast and mitochondria, but with no significant ultrastructural damage to the host cells.

Assuntos

Anti-Infecciosos/farmacologia , Antiprotozoários/farmacologia , Benzofuranos/farmacologia , Líquens/química , Trypanosoma cruzi/efeitos dos fármacos , Animais , Anti-Infecciosos/isolamento & purificação , Antiprotozoários/isolamento & purificação , Benzofuranos/isolamento & purificação , Macrófagos Peritoneais/parasitologia , Macrófagos Peritoneais/ultraestrutura , Camundongos , Microscopia Eletrônica , Mitocôndrias/parasitologia , Mitocôndrias/ultraestrutura , Trypanosoma cruzi/ultraestrutura

RESUMO

Microparticles will probably play a promising role in the future of chemotherapy. These polymeric delivery systems are capable of maximizing the therapeutic activity while reducing side effects of anti-cancer agents. Usnic acid (UA) is a secondary metabolite produced by lichens, which exhibits an anti-tumour activity. In this study, PLGA-microspheres containing usnic acid from Cladonia substellata were prepared by the double emulsion method, with or without PEG as stabilizer. The morphology of the microspheres was examined by optical and scanning electron microscopy. The in vitro kinetic profile of usnic acid loaded-microspheres was carried out by dissolution testing. The usnic acid content was analysed by HPLC. The cytotoxicity of free and encapsulated usnic acid was evaluated against HEp-2 cells using the MTT method. The anti-tumour assay was performed in mice against Sarcoma-180 tumour (UA 15 mg kg(-1) weight body/day) during 7 days. Animals were then sacrificed and tumour and organs were excised for histopathological analysis. Microspheres presented a smooth spherical surface with a mean diameter of 7.02 +/- 2.72 microm. The usnic acid encapsulation efficiency was approximately 100% (UA 10 mg 460 mg(-1) microspheres). A maximum release of 92% was achieved at the fifth day. The IC50 values for free and encapsulated usnic acid were 12 and 14 microg ml(-1), respectively. The encapsulation of usnic acid into microspheres promoted an increase of 21% in the tumour inhibition as compared with the free usnic acid treatment. In summary, usnic acid was efficiently encapsulated into PLGA-microspheres and the microencapsulation improved its anti-tumour activity.

Assuntos

Antineoplásicos/farmacologia , Benzofuranos/farmacologia , Animais , Antineoplásicos/análise , Antineoplásicos/uso terapêutico , Benzofuranos/análise , Benzofuranos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Portadores de Fármacos , Composição de Medicamentos/métodos , Ácido Láctico , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos , Microscopia Eletrônica de Varredura , Microesferas , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros , Sarcoma 180/tratamento farmacológico

RESUMO

We investigated the presence of free mRNA in the plasma of patients with chronic myeloid leukemia (CML), through RT-PCR analysis of G3PDH, a metabolism gene. We also analysed the presence of mRNA for HLM, a human oxysterol-binding protein homologue recently described as a potential marker for blood dissemination of solid tumors. Our results showed the presence of metabolism G3PDH mRNA in the plasma of 5/11 (45%) CML patients studied but HLM mRNA was not detected in any of the plasma studied. HLM mRNA was detected in the leukocytes of 4/5 (80%) CML patients. This work reports for the first time free mRNA in the plasma of CML patients. Our results also suggest that the detection of HLM could be a potential molecular marker for the follow-up in hematological malignancies.

Assuntos

Gliceraldeído-3-Fosfato Desidrogenases/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , RNA Mensageiro/análise , RNA Neoplásico/genética , Receptores de Esteroides/genética , Primers do DNA/química , Eletroforese em Gel de Poliacrilamida , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucócitos/metabolismo , RNA Mensageiro/sangue , RNA Neoplásico/sangue , Receptores de Esteroides/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa

RESUMO

The chemical composition of fatty acids and ubiquinones was studied in 18 strains of Cunninghamella, to establish quantitative and qualitative differences within the genus. Fatty acids analysis has shown the presence of four groups. Ubiquinone analysis, through high performance liquid chromatography (HPLC), demonstrated the existence of three different groups based on the ubiquinone type. The average percentage of fatty acids of the species Cunninghamella elegans and Cunninghamella bertholletiae, show variations in linolenic and stearic acids, suggesting the possibility of differentiation between the two species.