Dissertações em Ciências Farmacêuticas (Mestrado) - PPGCF/ICS
URI Permanente para esta coleçãohttps://repositorio.ufpa.br/handle/2011/2313
O Mestrado Acadêmico em Ciências Farmacêuticas teve início em 2005 e homologado pelo CNE e funciona no Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF) do Instituto de Ciências da Saúde (ICS) da Universidade Federal do Pará (UFPA).
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Item Acesso aberto (Open Access) Abordagem fitoquímica, determinação da atividade antiplasmódica in vitro e avaliação preliminar da toxicidade do extrato hidroetanólico das cascas de Aspidosperma excelsum Benth (Apocynaceae)(Universidade Federal do Pará, 2011) GOMES, Luis Fábio dos Santos; DOLABELA, Maria Fâni; http://lattes.cnpq.br/0458080121943649; VASCONCELOS, Flávio de; http://lattes.cnpq.br/3695753129639448Malaria is a disease caused by protozoa of the genus Plasmodium. The treatment of malaria is becoming increasingly difficult with the expansion of the cases of parasites resistant to drugs used in therapy. In this context, products isolated from plants have give an important contribution, representing an important source for obtaining new antimalarial drugs. Antiplasmodial activity of alkaloids of plant origin has been widely reported in the literature. Plants of the Apocynaceae family, rich in indole alkaloids have medicinal properties and some large species of the genus Aspidosperma have demonstrated antimalarial potential. Thus, this study aimed to perform a phytochemical approach, evaluate the antiplasmodial activity and toxicity in vitro preliminary of the hydroethanolic extract from the bark of A. excelsum, native of the Amazon region, where it is traditionally used to treat various diseases, including malaria. Antiplasmodial activity in vitro of different concentrations of the extract and alkaloidal and methanolic fractions was evaluated in cultures of P. falciparum W2 by the percentage of inhibition of parasitaemia and the mean inhibitory concentration (IC50) was determined at intervals of 24, 48 and 72 h. The cytotoxicity assay of the extract and alkaloidal fraction was carried out on L929 mouse fibroblasts by MTT method and the testing of acute oral toxicity of the extract was carried out according to the Fixed Dose Procedure adopted by the OECD with small modifications. The phytochemical approach revealed the presence of saponins, reducing sugars, phenols and tannins and alkaloids, and these were confirmed in significant amounts in the alkaloidal fraction with chloroform fraction (C2). Through thin layer chromatography and high performance liquid chromatography of the extract characterized the presence of the indole alkaloid yohimbine. The extract and fractions showed antiplasmodial activity in vitro. The extract showed the best activity in 24 h (IC50 = 5.2 ± 4.1 μg / mL), indicating a good activity schizonticide. Only C2 alkaloidal fraction showed a small but significant cytotoxicity (concentrations higher than 800 μg/mL). The extract not only cytotoxicity but also did not showed any obvious sign of toxicity in acute oral dose of 5000 mg/mL. The results indicate that the extract of Aspidosperma excelsum Benth presents promising potential antimalarial and deserves more detailed studies on antiplasmodial activity, aiming the isolation of active compounds and elucidation of their mechanisms of action.Item Acesso aberto (Open Access) Avaliação antifungica, farmacognóstica e toxicológica sazonal de Petiveria alliacea L. (Phytolaccaceae)(Universidade Federal do Pará, 2012-12-20) OLIVEIRA, Fábio Rodrigues de; GONÇALVES, Ana Cristina Baetas; http://lattes.cnpq.br/6886126078022769; ANDRADE, Marcieni Ataíde de; http://lattes.cnpq.br/8514584872100128The study of medicinal plants raised great scientific interest, mainly due to them being considered as potential sources of bioactive molecules with differentiated structure and new mechanism of action. The importance of research focused on the discovery and production of new herbal medicines should be the great contribution they have presented before diverse pathologies. The species Petiveria alliacea is a medicinal plant widely used by the population of the Amazon region and stands out for presenting various claims and still use some classes of metabolites with proven therapeutic actions. This study aimed to evaluate seasonal pharmacognostical parameters, antifungal potential of the extracts produced at different sampling times on Aspergillus species and toxicity of these in vitro and in vivo. In the evaluation of seasonal Pharmacognostical, P. alliacea, using Brazilian Pharmacopeia methods the results demonstrated reproducible parameters for quality control of the plant drug, there was no difference in the presence of the chemical constituents of hydroalcoholic and dust, revealing the presence of saponins, alkaloids and sugars across the plant and root extracts and only sesquiterpenolactones depsides. The results of microdilution method performed with extracts from the roots of two periods, showed weak antifungal activity in vitro, but did not observe any effect of extracts of the aerial parts. The cytotoxicity was evaluated by MTT colorimetric method, showed that the hydroalcoholic extract of the root of the two periods did not reduce cell viability in any of the concentrations tested, and was any signs of acute toxicity of the extract at a dose of 5000 mg/kg in mice. These data are considered relevant and the current study showed that P. alliacea is a promising medicinal species, but further investigations are required for its various allegations are confirmed and usage for the plant to be used in developing a new phytotherapeutic agent.Item Acesso aberto (Open Access) Avaliação da atividade antimicrobiana de extratos de própolis em diferente maturação(Universidade Federal do Pará, 2013-11-29) CHADA, Fabio José Garcia; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390The discovery and synthesis of antimicrobial comprise an element of paramount importance to health, however some of these substances have become obsolete due to the emergence of resistant microorganisms conventional therapy. Within the forms of treatment, natural products are an inexhaustible source of substances, including propolis, which is known worldwide due to its antimicrobial activity. The objective of this study was the microbiological analysis of six propolis samples collected from regions Prudentópolis - PR , at different times of deposit hive, with up to 40 days of deposit (New Propolis) and another with over 180 days (Propolis old). The antimicrobial activity was observed against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Micrococcus luteus and Enterococcus faecalis through testing microdilution plate with colorimetric assay using resazurin. At the end of the tests gave values ranging from 0.38 to 0.68 mg/ml to MIC new propolis and 0.34 to 1.3 mg/ml for the old to the microorganisms S. aureus and M. luteus having values close to both of these as well as the CBM between 0.38 to 1.62 and from 0.67 to 2.6 mg/ml, respectively. Similarly, for E. faecalis MIC values between 0.76 and 2.73 mg/ml for the new propolis and 2.72 and 1.34 mg/ml of the propolis old were made, and MBC values of 1.50 to 3.07 and 2.68 to 3.11 mg/ml, respectively, for samples 1V, 2N and 5N 5V CBM not observed for the concentrations studied. Gram- negative microorganisms were not sensitive to propolis. We conclude that the new propolis showed better antimicrobial activity, especially against S. aureus and M. luteus. However, the data also show that the values of MIC and MBC were very close between the different propolis, which was not evident reasons why the old propolis is discarded.Item Acesso aberto (Open Access) Avaliação da atividade antinociceptiva e anti-inflamatória de Mikania lindleyana DC: validação do uso na medicina popular(Universidade Federal do Pará, 2011-06-20) SILVA, Andressa Santa Brigida da; BARBOSA, Wagner Luiz Ramos; http://lattes.cnpq.br/1372405563294070; SOUSA, Pergentino José da Cunha; http://lattes.cnpq.br/9909053957915090Mikania lindleyana DC. (Asteraceae), popularly named sucuriju, is a common plant in Brazilian Amazonia. Ethnopharmacological studies show a diversity of uses of this species such in treatment of gastritis, infection, pain and inflammation. To validate the claim form and use was decided to study the acute toxicity and the antinociceptive and anti-inflammatory activities in experimental animal models and the chemical composition of lyophilized crude aqueous extract of Mikania lindleyana (AEML). The phytochemical screening of AEML showed the presence of saponins, proteins, amino acids, phenols, tannins, organic acids and flavonoids. On the thin layer chromatography (TLC) blues fluorescence characteristics of the coumaric acid were identifieds. The analisis on high-performance liquid chromatography coupled to mass spectrometry (HPLC-DAD-MS) seems compounds highly glycosylated. The dose 5000mg/kg of EAML did not cause death in animals. The AEML, at doses 125, 250, 500, 750, 1000 and 1500mg/kg, significantly inhibited (in a dose-dependant way) the number of contortions induced by acetic acid on writhing test. The median effective dose (ED50) of 692.6 mg/kg did not prolong the latency-time in the hot plate. The AEML showed activity in both first and second phase of formalin-induced licking response decreasing of the lick paw of mice, where this effect was reversed by the opioid antagonist naloxone. The AEML was able to inhibite the erythema formation when compared to control group, but did not inhibite the paw edema formation induced by dextran. The AEML inhibited the paw edema carrageenan-induced from 2nd hour and reduced neutrophil migration to peritoneal cavity. Our results indicate that AEML demonstrate an antinociceptive effect with probable involvement of the opioid system, and anti-inflammatory activity through inhibition of prodution of inflammatory mediators as PGs, and also on adhesion molecules with involvement of cytokines.Item Acesso aberto (Open Access) Avaliação da atividade antinociceptiva e antiinflamatória do óleo essencial de Hyptis crenata (Pohl) ex Benth(Universidade Federal do Pará, 2008-11-07) BRAVIM, Luciana Silva; MAIA, José Guilherme Soares; http://lattes.cnpq.br/1034534634988402; SOUSA, Pergentino José da Cunha; http://lattes.cnpq.br/9909053957915090Hyptis crenata (Pohl) ex Benth. is a herbaceous aromatic and medicinal plant, belongs to Lamiaceae, popularly known as salva-do-marajó, malva-do-marajó and hortelã-bravo. This plant is distributed since the mouth of Amazonas River, Marajó Island, Pantanal, and extending up to the states of Minas Gerais. Its essential oil is characterized by presence of monoterpenes and sesquiterpenes. The leaf tea is used as sudorific, tonic, stimulant, as well as to treat the eyes and throat inflammation, constipation and arthritis. Based in these information, we decided to evaluate the antinociceptive and anti-inflammatory activity of the oil (HcEO) of Hyptis crenata in mouse throught the following tests: abdominal constriction, hot plate, formalin, croton oil-induced ear edema, rat paw edema induced by dextran and carrageenan, carrageenan-induced peritonitis. The statistical method used in this study was ANOVA followed by multiple comparison (Student-Newman-Keuls test or Student t test). The essential oil was extracted by hydrodistillation, yield was 0,6% and their main components were monoterpenes (94,5%). The lethal dose (DL50) was 5000 mg/kg. In the abdominal constriction test, at doses of 250, 350 and 500 mg/kg, the HcEO inhibited the abdominal constrictions in 22,56%, 60,76% and 75,53%, respectively, in a dose-dependent manner when compared to the control group. The DE50 calculated was 364,22 mg/kg with a correlation coefficient of 0,9341. The oil not changed significantly the time of latency in the hot plate test. HcEO (364,22 mg/kg) caused an inhibition of the phase I in 26,42% and an inhibition of the phase II in 43,86% of the formalin test. Naloxone, an antagonist of opioid receptor, reverted the analgesic effect of EOHc. HcEO reduced croton oil-induced ear edema in 44,26%. In rat paw edema induced by dextran, HcEO produced inhibition at the dose of 364,22 mg/kg, but the rat paw edema induced by carrageenan this inhibition was not observed. In carrageenan-induced peritonitis, HcEo significantly decreased the leucocyte and neutrophil migration in 47,55% e 66,47%, respectively. Based on the results we are suggesting that the essential oil of H. crenata has an antinociceptive activity.It is probably as consequence of direct action on the nociceptive fiber, as well as the opioid system is involved in this effect. Further, our results suggest that anti-inflammatory activity of HcEO is probably of peripheral origin. It can be suggested, too, that the possible components responsible for these actions are the compounds monoterpenes presents in HcEO.Item Acesso aberto (Open Access) Avaliação das atividades antinociceptiva e anti-inflamatória do extrato hidroetanólico de partes aéreas de Portulaca pilosa L. (Portulacaceae)(Universidade Federal do Pará, 2012-08-30) FERREIRA, Fabrício Alexopulos; DOLABELA, Maria Fâni; http://lattes.cnpq.br/0458080121943649; SOUSA, Pergentino José da Cunha; http://lattes.cnpq.br/9909053957915090This study investigated the acute oral toxicity, the antinociceptive effect in chemical and thermal nociception models as such as the anti-inflammatory activity in carrageenan and croton oil models of the hydroethanolic extract from aerial parts of Portulaca pilosa (HEEPp). Also identified some possible mechanism involved in antinociception of the extract as such as the effects of HEEPp on central nervous system of rats. In the oral acute toxicity test, the treatment with HEEPp ( 2000 mg/kg) caused no deaths. In the acetic acid-induced writhing test, the HEEPp (100, 200, 400 and 600 mg/kg) administered by oral route (p.o.) significantly reduced the number of contortions acetic acid-induced in 18.18, 33.25, 47.27, 65.81 e 73.94%, respectively. In the hot plate test, the treatment with HEEPp (200, 400 e 600 mg/kg, p.o.) did not alter the latency to the thermal stimuli of 50 ± 0,5 ºC. In the formalin test, the treatment with HEEPp (200, 400 e 600 mg/kg, p.o.) significantly reduced the licking-time in neurogenic phase (first phase) in 38.79, 60.61 and 75.18 %, and inflammatory phase (second phase) in 49.23, 53.03 e 87.53 %, respectively. The previous naloxone administration, significantly reversed the effect of HEEPp (600 mg/kg, p.o.) in both phases of the formalin test. The pre-treatment with L-NAME and methylene blue significantly reversed the effect of HEEPp (600 mg/kg, p.o.) in both phases of the formalin test. The pre-treatment with glibenclamide also significantly reversed the effect of HEEPp (600 mg/kg, p.o.) in both phases of the formalin test. HEEPp (600 mg/kg, p.o.) did not affect the locomotor activity of rats in the open field test. In the carrageenan-induced paw edema and croton-induced ear edema, the HEEPp (400 and 600 mg/kg, p.o.) did not inhibit significantly the edema formation in both the tests. The results of this study showed that HEEPp, when administered by oral route, presented low toxicity and its antinociceptive actuation observed in neurogenic phase involves peripherals interaction with opioids receptors and activation of the in the NO/GCs/GMPc/ KATP pathway. Already the antinociceptive activity observed in the inflammatory phase does not seem to depend of the inhibition on via phospholipase A2/cyclooxygenases, but interaction with peripheral opioid receptors and the NO/sGC /cGMP/ KATP pathway.Item Acesso aberto (Open Access) Caracterização farmacognóstica e avaliação antifúngica das folhas de Chrysobalanus icaco (Lin) em espécies de Candida(Universidade Federal do Pará, 2012-09-12) PERES, Ana Regina Maués Noronha; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390; ANDRADE, Marcieni Ataíde de; http://lattes.cnpq.br/8514584872100128Currently, Candidiasis has stood out among fungal infections, due to its high incidence and mortality. In parallel, there is a greater record of microbial resistance and therapeutic failures presented by antifungals available. Chrysobalanus icaco Lin, a species native to the Amazon, has been popularly used in mycoses, without scientific evidence, so the importance of research to evaluate their antifungal properties. The analysis pharmacognostic of leaves of C. icaco indicated levels of loss on drying, total ash and ash insoluble 12.3% ± 0.0288, 4.31% ± 1.67% ± 0.0001 and 0.0012, respectively. Phytochemical screening of the hydroalcoholic extract of the leaves of C.icaco (EHCI) revealed the presence of organic acids, sugars, saponins, catechins, depsídeos, phenols, flavonoids, tannins, proteins, amino acids and purine. In HPLC analysis, it was dominated by the flavonoids, especially Myricetin. Antifungal activity was tested by microdilution opposite strain ATCC 40175 Candida albicans and eleven clinical isolates of oral Candida albicans, C. dubliniensis, C. parapsilosis and C. tropicalis. The MIC ranged from greater than 6.25 mg / mL to 1.5 mg / mL and CFM, when determined, was equal to or greater than 6.25 mg / mL. The EHCI showed moderate activity against the strain ATCC 40175 and the weak antifungal activity against clinical isolates mouth. These results open new perspectives for studies that investigate fractions and substances Chrysobalanus icaco with greater activity against Candida species.Item Acesso aberto (Open Access) Caracterização físico-química e avaliação toxicológica preliminar do copolímero sulfato de condroitina-co-N-isopropilacrilamida para uso farmacêutico(Universidade Federal do Pará, 2013-07-19) SANCHES, Suellen Christtine da Costa; COSTA, Roseane Maria Ribeiro; http://lattes.cnpq.br/0537372052713559; VASCONCELOS, Flávio de; http://lattes.cnpq.br/3695753129639448The pharmaceutical industry uses polymers as nanoparticles in controlled release formulations and vector for having low cost compared to other methods of preparation of pharmaceutical dosage forms, apparently not being recognized by the body's defense system, provide improved efficacy, reduce toxicity and the dose of administered drug. The sulfate of chondroitin-co-N-isopropylacrylamide (SCM + NIPAAm) is a copolymer proposed for this purpose, from a synthetic polymer reaction, poly Nisopropylacrylamide (PNIPAAm) with thermosensitive characteristics with a natural, Chondroitin sulfate (CS), with bioadhesive characteristics. Thus, the copolymerization may be able to add these properties and to improve its use as a vehicle for controlled-release. This study aimed to characterize physico-chemical of sulfate chondroitin particles and N-isopropylacrylamide and SCM+NIPAAm copolymer (2.5% and 5%) and SCM+PNIPAAm 2.5% and a partial toxicological evaluation of one of these copolymers presenting the best properties of an efficient carrier of drugs, selected from the trials of physic-chemical characterization. To determine the chemical structure of the particulate systems and analyze the chemical components, it was performed Nuclear Magnetic Resonance Spectroscopy (RMN) and Infrared Fourier Transformed Spectroscopy (FTIR), to analyze the morphology of the particles, it was used Electron Microscopy (SEM), The Thermogravimetry and Differential Thermal Analysis (TG/DTA) was used to evaluate the thermal behavior of particulate systems, as well as assist in the analysis of kinetics of degradation (CD, Flynn-Wall-Ozawa method); it was also made in vitro degradation technique and surface charge determining and particles size (Zeta potential analysis, PZ). To evaluate the toxicity, it was performed bioassay in Artemia salina (24 and 48 hours), cell viability (cytotoxicity) on PC-12 cells (MTT method), and also acute oral toxicity in mice. The NMR, FTIR and SEM analysis showed similarity regarding the structural and morphologic aspects between the studied copolymers. TG analyzes showed that SCM+NIPAAm 5% showed higher thermal stability compared to the other copolymers evaluated, since its polymer decomposition occurs at temperatures above around 233 °C. DTA demonstrated temperature values consistent with decomposition thermal events provided by the curves of TG analysis. The stability was confirmed by CD and in vitro degradation study, presenting, respectively, Ea> 100 kJ mol-1 and 48% of its initial weight after three months. Furthermore, SCM+NIPAAm 5% presented particle diameter of less than 200 nm and polydispersity index of 0.35, and the PZ> -30mV, characteristics of a promising candidate as a drug carrier. Regarding toxicological evaluations, SCM+NIPAAm 5% did not show toxicity on bioassay A. saline (LC50> 1000) and in the cellular model evaluated within the concentrations and circumstances of exposure studied. The SCM+NIPAAm 5%, in the oral dose of 2000 mg/kg, did not show any obvious sign of toxicity in mice, which was confirmed by the absence of anatomical and histopathological changes. The copolymerization of chondroitin sulfate and N-isopropylacrylamide in the studied concentration, given its physical-chemical characteristics and toxicological preliminary, presents properties that contribute to propose a system which is a new form of controlled release, especially drugs.Item Acesso aberto (Open Access) Composição química e efeitos antinociceptivo e antiinflamatório em roedores do óleo essencial de Peperomia serpens (Sw) Loud(Universidade Federal do Pará, 2011-06-20) PINHEIRO, Bruno Gonçalves; MAIA, José Guilherme Soares; http://lattes.cnpq.br/1034534634988402; SOUSA, Pergentino José da Cunha; http://lattes.cnpq.br/9909053957915090The Peperomia serpens (Piperaceae), popularly known as “carrapatinho”, is an epiphyte and herbaceous liana grown wild on different host trees in the Amazon rainforest. Its leaves are largely used in Brazilian folk medicine to treat inflammation, pain and asthma. This study investigated the effects of essential oil of P. serpens (EOPs) in standard rodent models of pain and inflammation. The antinociceptive activity was evaluated using chemical (acetic acid and formalin) and thermal (hot plate) models of nociception in mice whereas the anti-inflammatory activity was evaluated by carrageenan (Cg) - and dextraninduced paw edema tests in rats croton oil-induced ear edema, as well as cell migration, rolling and adhesion induced by Cg in mice. Additionally, phytochemical analysis of the EOPs has been also performed. Chemical composition of the EOPs was analyzed by gas chromatography and mass spectrometry (GC/MS). Twenty five compounds, representing 89.6% of total oil, were identified. (E)-Nerolidol (38.0%), ledol (27.1%), α-humulene (11.5%), (E)- caryophyllene (4.0%) and α-eudesmol (2.7%) were found to be the major constituents of the oil. Oral pretreatment with EOPs (62.5-500 mg/kg) significantly reduced the writhing number, with an ED50 value of 188.8 mg/kg that was used thereafter in all tests. EOPs had no significant effect on hot plate test but reduced the licking time in both phases of the formalin test, an effect that was not significantly altered by naloxone (0.4 mg/kg, s.c.). EOPs inhibited the edema formation induced by Cg and dextran in rats. In mice, EOPs inhibited the edema formation by croton oil as well as the leukocyte and neutrophil migration, the rolling and the adhesion of leukocytes. These data show for the first time that EOPs has a peripheral antinociceptive effect that seems unrelated to interaction with the opioid system and a significant anti-inflammatory effect in acute inflammation models.Item Acesso aberto (Open Access) Desenvolvimento de um método para caracterização do extrato hidroetanólico das folhas de Mikania lindleyana DC por Cromatografia Líquida de Alta Eficiência (CLAE)(Universidade Federal do Pará, 2011) OWITI, Alex Oselu; BARBOSA, Wagner Luiz Ramos; http://lattes.cnpq.br/1372405563294070Mikania lindleyana DC (Asteraceae), vernacular “Sucuriju”, is a creeping, shrubby, perennial, evergreen plant, growing in the Amazon region where it is used as diuretic, anti-hypertensive, anti-inflammatory and anti-ulcerous medicine. The main aim of this study was to develop a method for characterization of hydro-ethanolic extract (tincture) from the leaves of M. lindleyana DC, using UV and High performance Liquid Chromatography (HPLC). The hydro-ethanolic extract (tincture) was prepared based on Brazilian Pharmacopeia V, 2010 and its dry residue was submitted to phytochemical analyses, Thin Layer Chromatography (TLC) and High Performance Liquid chromatography (HPLC). Among the substances observed in the phytochemical analysis was coumarin, alkaloids, amino acids, reducing sugars, phenols, tannins, steroids, terpenes, saponins and organic acids. TLC test was done by applying hexanic, chloroformic and ethyl acetate Fractions together with Crude hydro-ethanolic extract and aqueous solution of coumarin Aldrich® 0,1mg/ml on the same plate using toluene/dichloromethane/acetone (45:25:30) as the eluent system. The chromatogram was then sprayed with an alcoholic solution of KOH 5%, and then observed under UV light at 254nm and 365 nm, revealing a light green band at an RF-0.61 for chloroformic fraction, crude hydro-ethanolic extract and for coumarin samples. The HPLC analysis was conducted using methanol/water 53:47 as the eluent system. The chloroformic fraction(CL), coumarin and the crude hydro-ethanolic extract (CHE) showed peaks at Retention time around 6.00minutes and spectra with maximum absorptions between 270nm and 300nm.This clearly demonstrate the presence of coumarins in the samples (CL= 0.209mg/mL and CHE= 0.014mg/mL).Item Acesso aberto (Open Access) Efeito da dapsona na geração de estresse oxidativo em pacientes com hanseníase em uso de poliquimioterapia(Universidade Federal do Pará, 2011) SCHALCHER, Taysa Ribeiro; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390Inflammation caused by Mycobacterium leprae infection and drugs with oxidative properties such as dapsone, are risk factors to induce the oxidative stress in leprosy patients. This study aims to determine plasma concentrations of dapsone in leprosy patients in use of multidrug therapy (MDT), correlating the development of oxidative stress. For the study, healthy individuals and leprosy patients were selected, followed before (D0) and after the third MDT-supervised dose (D3). The plasma concentrations of dapsone in patients under treatment (D3) were evaluated by high performance liquid chromatography. The oxidative stress was performed by methemoglobin (MetHb) and Heinz bodies determination, concentrations of reduced glutathione (GSH), nitric oxide (NO), malondialdehyde (MDA), total antioxidant capacity (TEAC) and enzymatic activity of catalase (CAT), superoxide dismutase (SOD) in blood. In the study were obtained 23 samples from leprosy patients in D0 and 13 in D3; and 20 healthy and without leprosy subjects. In patients before treatment (D0) were observed increase of NO (D0 = 18.91 ± 2.39, control = 6.86 ± 1.79mM) and significant reduction of the activity of SOD enzyme (D0 = 69.88 ± 12.26, control = 138.42 ± 14.99 nmol/mL). In MDT-treated patients (D3), the dapsone concentration in plasma was of 0,552 ± 0,037 μg / mL, and they showed Heinz bodies presence and significant increase in the MetHb percentage (D3 = 3.29 ± 0.74, control = 0051 ± 0.66%). In this patients also were observed increase of the GSH levels (D3=7.01 ± 1.9; control =3.33 ± 1.9 μg/mL) and decrease of the CAT activity (D3 = 10.29 ± 02.02, control = 19:52 2:48 ± U / g protein). However, MDA levels in D0 and D3 patients didn’t show changed, while TEAC levels, in this patients, significantly increased (D0 = 2.90 ± 0.42; D3 = 3.04 ± 0:52, control = 1.42 ± 0.18 μmol / mL). These data suggest that the MDT is mainly cause for oxidative stress, because it induced the generation of oxidative damage identified by Heinz bodies’ presence and increase in the MetHb percent.Item Acesso aberto (Open Access) Estudo da ação antinociceptiva e antiinflamátoria do 1-Nitro-2-Feniletano, principal constituinte da Aniba Canelilla(Universidade Federal do Pará, 2008-06-26) LIMA, Anderson Bentes de; MAIA, José Guilherme Soares; http://lattes.cnpq.br/1034534634988402; SOUSA, Pergentino José da Cunha; http://lattes.cnpq.br/9909053957915090Aniba canellila is a large size tree found in Northern region of Brazil and largely used in folk medicine. The infusate of its leaves and bark skin is believed to be a good antispasmodic, antidiarreic, anti-inflammatory, tonic agent and a good stimulant of digestive and the central nervous systems. This study was designed to evaluate the effects 1-nitro-2-phenylethane, main component of Aniba canelilla. We evaluated the antinociceptive and anti-inflammatory effects of the 1-nitro-2-phenylethane which is the main component of essential oil of Aniba canelilla. For nociception models were designed the writhing test, hot plate test and formalin test. For inflammation models were designed the croton oil-induced ear edema, rat paw edema induced by carrageenan and dextran, and leucocyte and neutrophil migration on carrageenan-induced peritonitis. In the writhing test, the 1-nitro-2-phenylethane dosed at 15, 25 and 50 mg/kg reduced the abdominal writhes in a significant manner. In the hot plate test (55 ? 0.5? C), the 1-nitro-2-phenylethane dosed at 50, 100 and 200 mg/kg did not induced alterations in the latency time when compared to the control. In the formalin test, the 1-nitro-2-phenylethane dosed at 50 and 25 mg/kg reduced in a significant manner the second phase of the algic stimulous. In addition, its antinociception was reversed by naloxone in the second phase. The 1-nitro2-phenyletahne produced inhibition of rat paw edema induced by carrageenan and dextran in a dose-dependent manner at the doses of 25 and 50 mg/kg. Doses of 25 and 50 mg/kg caused a dose-dependent inhibition of croton oil-induced ear edema in mice (with inhibition of 73% and 79%, respectively). Pretreatment (60 min) of rats with 1-nitro-2-phenylethane (25 mg/kg) significantly decreased leucocyte and neutrophil migration on carrageenan-induced peritonitis (with inhibition of 22,55% and 38,13%, respectively). Our results suggest that 1-nitro-2-phenylethane has analgesic activity which, according to the tests employed, is probably of peripheral origin. The mechanism involved is not completely understood, however these results suggest that opiod receptors are involved in the antinociceptive action of the 1-nitro-2-phenylethane. Further, our results suggest that 1-nitro-2-phenylethane has anti-inflammatory activity which, according to the tests employed, is probably of peripheral origin.Item Acesso aberto (Open Access) Estudo fitoquímico e atividade antiplasmódica em Plasmodium falciparum (W2) de Himatanthus articulatus (Vahl) Woodson (Apocynaceae)(Universidade Federal do Pará, 2014-10-15) VALE, Valdicley Vieira; DOLABELA, Maria Fâni; http://lattes.cnpq.br/0458080121943649; OLIVEIRA, Alaide Braga de; http://lattes.cnpq.br/3719659803766075The present master thesis describes the phytochemical study and the antiplasmodial activity against Plasmodium falciparum (W2) of Himatanthus articulatus (Vahl) Woodson. The ethanol extract (EEHS) obtained by percolation of the bark powder, gave, after concentration, a precipitate (EEHSP) and a pasty residue that was submitted to lyophilization (EEHS). Fractionation of EEHS was carried out by successively re-extraction with DCM, AcOEt and MeOH under reflux, by acid-base partitioning for separation of alkaloids and by chromatography over silica gel column. Furthermore, the bark powder was extracted with 1 N HCl for the separation of alkaloids. TLC prospection of EEHS and EEHSP was carried out while EEHS, FrDCM EEHS, FrAcOET EEHS, FrMeOH EEHS and FAHS2 DCM were also analyzed by HPLC - DAD. Column chromatography of FrAcOET EEHS afforded a substance (S1). EEHS, the major fraction obtained in its chromatographic column (F71), DCM FAHS2 and S1 were analysed by UPLC-PDA-MS/ESI. Spectroscopic analyses of S1 (IR, UV, MS/ESI, 1H and 13CNMR) allowed its identification as plumieride. Antiplasmodial activity against P. falciparum (W2) was evaluated for EEHS, EEHSP, FrDCM EEHS, FrAcOET EEHS, FrMeOH EEHS, FAHS1 DCM, DCM FAHS2, FAEEHS, FNEEHS, FNHS DCM and S1 by the parasite lactate dehydrogenase (pLDH) method. In the TLC prospection, EEHS and EEHSP showed positive results for polyphenols and tannins, saponins, triterpenes and steroids, alkaloids and flavonoids. EEHS fractions were analyzed by HPLC-DAD showing suggestive peaks of iridoids. Analyses by UPLC-PDA-MS/ESI showed that EEHS contains plumieride as the major substance whose psedomolecular peak was observed at m/z 471 (M + H). S1 was identified as plumeride. Until now it was not reported the presence of alkaloids for the species but spots suggestive of alkaloids were observed on TLC with Dragendorff reagent of FAHS1 DCM, DCM FAHS2, FAEEHS, FNEEHS and FNHS DCM were observed. UV spectra registered online by HPLC-DAD for FAHS2 showed that the major peak is suggestive of a β-carboline alkaloid. UPLC-PDA-MS/ESI analysis of FAHS2 DCM showed an intense peak corresondng to a pseudomolecular ion 329 u that could be possibly attributed to the alkaloid 10-hydroxy-antirine-N-oxide (MM 328 u). The antiplasmodial assays were negative for EEHS, EEHSP, FrDCM EEHS, FrAcOET EEHS, FrMeOH EEHS, S1, FAEEHS, FAHS1 DCM, FNEEHS, FNHS DCM and moderately active (CI50 22,89 μg/mL) for FAHS2 DCM. These results indicate that the antiplasmodial activity might be attributed to the plant alkaloids whose presence in H. articulatus is reported here by the firist time.Item Acesso aberto (Open Access) Estudo fitoquímico, avaliação da toxicidade oral aguda e da atividade antimalárica in vitro e in vivo das cascas de Parahancornia fasciculata (Poir.) Benoist (Apocynaceae)(Universidade Federal do Pará, 2013) SILVA, Adreanne Oliveira da; OLIVEIRA, Alaíde Braga de; http://lattes.cnpq.br/3719659803766075; DOLABELA, Maria Fâni; http://lattes.cnpq.br/0458080121943649Parahancornia fasciculata (Poir.) Benoist (Apocynaceae), also known as Parahancornia amapa (Hub.) Ducke is a species used in the treatment of malaria, uterus infections, gastritis, anemia, respiratory problems, among other ailments. The objectives of this study were to carry out the phytochemical study of the trunk bark from P. fasciculata, to evaluate the in vitro and in vivo antimalarial activity as well as the acute oral toxicity of extracts and fractions from this plant species. The powder bark of P. fasciculata was submitted to extractions by maceration/percolation with ethanol 96% and with dichloromethane after alkalinization of the bark powder affording the dry extracts EEPF and EDAPF, respectively. EEPF underwent two different re-extractions: 1) acid-base extractions affording the neutral (EEPFN) and alkaloidal fractions (EEPFA) and 2) heating under reflux with different solvents, leading to the fractions EEPF-DCM:HEX (1:1), EEPF-DCM: AcOEt (1:1) and EEPFinsoluble in AcOEt. Phytochemical screening of EEPF by TLC revealed the presence of triterpenes and steroids, flavonoid heterosides, saponins, polyphenols, tannins, anthracene heterosides and cardiotonic heterosides. EDAPF was submitted to chromatography through a silica gel column to give 30 fractions of which Fr1-3, Fr4, Fr5-7 and Fr11 represented most of the extract that was chromatographed. Fr5-7 led to the isolation of a mixture of esters of lupeol which are the major components of this extract. Saponification of this fraction afforded Fr5-7Hid that was analyzed by IV, 1H and 13CNMR and was identified as the triterpene lupeol. The insoluble AcOEt fraction derived from re-extraction of EEPF gave a positive test for proanthocyanidins which were quantitatively determined and the results were expressed in percentage for the content of these metabolites in an undiluted sample (10,46 ± 0,3419 %), a 1:10 diluted sample (9,94 ± 0,1598 %) and a 1:100 diluted sample (10,55 ± 0,9299%). The evaluation of the antiplasmodial activity in vitro was carried out against W2 strains of Plasmodium falciparum by the assay of the Histidine-Rich Protein II (HRPII) with EEPF, EEPFN, EEPFA, Fr1-3, Fr4, Fr5-7 (lupeol esters), Fr11 and Fr5-7Hid (lupeol). The best result was obtained for EEPF, EEPFA, EEPFN (CI50 = ~ 50 μg / mL) that can be considered as moderately active. The remaining samples showed CI50 > 50 μg / mL and were considered inactive. The in vivo antimalarial activity was performed in Swiss female mice infected with ANKA strains of Plasmodium berghei with EEPF and EEPF-DCM:HEX (1:1) at concentrations of 500, 250 and 125mg/kg body weight. EEPF was partially active only on the 8th day in all concentrations tested while EEPF-DCM:HEX (1:1) was partially active at a dosis of 500mg/kg and was inactive in the remaining doses. The acute oral toxicity test was determined for EEPF in Swiss female mice by the method of the fixed dose (5,000mg/kg) when no apparent signs of toxicity were observed what was confirmed by the absence of anatomic and histopathologic changes.Item Acesso aberto (Open Access) Estudos de citotoxicidade e genotoxicidade de Eleutherine plicata Herb(Universidade Federal do Pará, 2014-09-30) GALUCIO, Natasha Costa da Rocha; BAHIA, Marcelo de Oliveira; http://lattes.cnpq.br/3219037174956649; DOLABELA, Maria Fâni; http://lattes.cnpq.br/0458080121943649The purpose of this study was phytochemical studies of E. plicata, and to evaluate the cytotoxicity, the role of oxidative stress and genotoxicity. The powder of E. plicata bulbs underwent maceration with ethanol, the solution concentrated to residue in rotaevaporator. The ethanol extract was subjected to fractionation by open column chromatography over silica gel, being used as the mobile phase solvents of increasing polarity. The dichloromethane fraction was subjected to fractionation by preparative layer chromatography using dichloromethane as mobile phase, and 3 subfractions obtained. The ethanol extract, fractions and subfractions were subjected to chromatographic and spectrophotometric analysis. All samples were subjected to the tests: cellular viability (MTT), the antioxidant capacity (DPPH), comet and micronucleus assays. From the ethanol extract obtained a rich fraction naphthoquinone (dichloromethane fraction). Fractionation of this led to the isolation of: S1, S2 (major fraction), and fraction of minority S3 (unidentified, not tested). Chromatographic studies and spectrophotometric allowed the identification of S2 (isoeleuterin). Fractionation contributed positively to cytotoxicity on VERO cells, the sample being more cytotoxic to S1. The cytotoxicity in HepG2 cells was concentration dependent, being the fractionation did not contribute positively to this. Also, over time, the longer the exposure time, the lower the cytotoxicity to HepG2 cells. The maximum antioxidant activity was observed for subfraction S1, and this low genotoxicity possessed by both methods and it was the most cytotoxic. The dichloromethane fraction has an intermediate antioxidant capacity, but had a high genotoxicity in micronucleus assay. The isoeleuterin (S2) was lower antioxidant capacity, lower cytotoxicity and genotoxicity conflicting results. The ethanol extract possessed the lowest antioxidant capacity, moderate genotoxicity and lower cytotoxicity. When analyzing the results occur that: a subfraction S1 is the most promising candidate as the antimalarial drug, as have cytotoxicity and genotoxicity rates at acceptable levels. The isoeleuterin needs additional research on 11 genotoxicity. Regarding the dichloromethane fraction was not advisable to use for the development of an antimalarial drug, since it is more genotoxic.Item Acesso aberto (Open Access) Investigação dos prejuízos motores decorrentes da exposição crônica ao etanol, em ratas intoxicadas da adolescência à fase adulta(Universidade Federal do Pará, 2013-09-19) SILVA, Fernando Bezerra Romualdo da; MAIA, Cristiane do Socorro Ferraz; http://lattes.cnpq.br/4835820645258101According to the World Health Organization, ethanol is the most widely used psychoactive drug in the world, occupying a prominent place by now be considered a public health problem worldwide. His heavy drinking among adolescents is on the rise, from 15 years and young adults A wide variety of research related to its damaging many organs and body systems effects, as well as damage and degeneration of the central nervous system structures, and the cerebellum one of its main targets is the affinity of the substance for cellular structures is the ability to generate a cascade of deleterious processes . The aim of this study was to evaluate behavioral changes associated with the cerebellum in rats chronically intoxicated with ethanol adolescence to adulthood. Female at 35 days of postnatal life received during 55 days, ethanol by gavage. After this period of intoxication, the animals underwent a battery of tests to assess motor deficits. Behavioral tests consisted Open Field, Pole Test, Walking Beam and Rotarod. The results showed that animals exposed to ethanol displayed motor deficits in all behavioral tests. Although several mechanisms are associated with cerebellar degeneration, further studies should be conducted to investigate the true effect of this drug and their correlation wiser the results obtained in this research.Item Acesso aberto (Open Access) Minociclina atenua os prejuízos motores em ratos submetidos à isquemia focal no córtex motor e expostos cronicamente ao etanol da adolescência à fase adulta(Universidade Federal do Pará, 2012-08-30) OLIVEIRA, Gedeão Batista de; MAIA, Cristiane do Socorro Ferraz; http://lattes.cnpq.br/4835820645258101According to World Health Organization, alcohol consumption in the world has become a public health problem. In this context, Brazil is at 63th position in the world in per capita alcohol consumption for people aged 15 or older. In addition to its socio-economic effects, ethanol is an important risk factor in the occurrence of cerebral ischemia. Exacerbated consumption of this drug contributes to the poor prognosis, as well as possible treatment for health problems related to stroke. The objective of this study was to evaluate neuromotor changes after blocking micróglial activation with minocycline in rats subjected to focal ischemia in the motor cortex, when treated chronically with ethanol from adolescence to adulthood. Rats were given for 55 days by gavage ethanol (6.5 g/kg/dia, 22.5 w/v). At the end of 55 days the animals were microinjected with the vasoconstrictor peptide endothelin-1 (40 pmol) for induction of focal ischemic lesion. The ischemic animals were treated with minocycline receiving two daily doses of 50 mg/kg in the first two days, and five daily applications of single 25mg/kg, intraperitoneally, by the seventh day post-ischemic induction. Behavioral tests consisted of open field, inclined plane and rota-rod. The results showed that the animals were exposed to ethanol showed motor deficits in all behavioral tests. However, treatment with minocycline was able to reverse them, enabling better performance on all tests. The results suggest that minocycline was able to reverse damage caused by motors stroke, even in the presence of ethanol. The exact mechanism involved in this process need to be investigated in future research.