Programa de Pós-Graduação em Ciências Farmacêuticas - PPGCF/ICS

URI Permanente desta comunidadehttps://repositorio.ufpa.br/handle/2011/2312

O Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF) vinculado ao Instituto de Ciências da Saúde (ICS) da Universidade Federal do Pará (UFPA) apresenta um auto-impacto de inserção regional uma vez que se trata do único PPGCF na Região Norte pelo grande potencial de utilização da biodiversidade na região amazônica. Além de favorecer a fixação e atração de profissionais qualificados na área de Ciências Farmacêuticas na Região Amazônica.

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Agora exibindo 1 - 20 de 29

Acesso aberto (Open Access)
Acetilbergenina: obtenção e avaliação das atividades antinociceptiva e anti-inflamatória
(Universidade Federal do Pará, 2010-01-22) BORGES, Jaqueline Cibene Moreira; SOUSA, Pergentino José da Cunha; http://lattes.cnpq.br/9909053957915090; SANTOS, Lourivaldo da Silva; http://lattes.cnpq.br/3232898465948962
Endopleura uchi (Huber) Cuatrec. (Humiriaceae), a Brazilian Amazon plant, commonly known as “uxi”, is used in folk medicine for the treatment of several pathologies, such as arthritis. Bergenin, one of the chemical constituents of E. uchi, has several biological activities, including anti-inflammatory and antinociceptive activities. In order to obtain a more potent derivative than bergenin it has decided to acetyl this substance. Acetylbergenin was tested in nociception and inflammation models. Bergenin was isolated from the chromatographic fractionation of aqueous extract from stem bark of E. uchi and the acetylbergenin was obtained by acetylation of bergenin. The substances were identified based on spectral analysis of 1H NMR, 13C NMR, DEPT and COSY, and comparison with literature data. For nociception models were carried out the abdominal writhing test, hot plate test and formalin test, while in the inflammation models were carried out the croton oil-induced ear edema, rat paw edema induced by carrageenan and dextran, carragenin-induced peritonitis test. Furthermore, the model of gastric ulcer induced by stress was used to assess the potential ulcerogenic of the substance. In the abdominal writhing test induced by acetic acid 0.6%, acetilbergenin doses of 1, 5, 10, 15 and 25 mg / kg blocked the number of writhing in 28.2%, 52.7%, 61.1 %, 68.3% and 95.0%, respectively, and dose-dependent manner when compared to the control group. The calculated ED50 was 6.8mg/kg. In the hot plate test (55ºC), acetylbergenin (6.8 mg/kg) did not induce alterations in the latency time when compared to the control group. In the formalin test, acetylbergenin (6.8mg/kg) inhibited 88.30% the algic stimulus in the second phase (inflammatory) compared to the control group. Furthermore, naloxone reversed the effect of acetylbergenin the second phase of this test. In the croton oilinduced dermatitis, acetylbergenin (6.8 mg/kg) provoked inhibitory effect in 75.60% in comparison to the control group. In the paw edema induced by carrageenan, acetylbergenin (6.8 mg/kg) was able to reduce the development of edema from the 2nd to the 5th hours compared to the control group. In the paw edema induced by dextran, acetylbergenin (6.8 mg/kg) reduced edema at all times. In carragenininduced peritonitis, acetylbergenin (6.8mg/kg) blocked 70% of the neutrophils number compared to the control group. In the trial of gastric ulcer, acetylbergenin blocked 78.55% in the generation of gastric lesions by stress when compared to indomethacin. The results suggest that acetylbergenin has an antinociceptive and anti-inflammatory activity which, according to the tests employed, is probably of peripheral origin.
Acesso aberto (Open Access)
Atividade anticolinesterásica dos óleos essenciais e componentes majoritários de Piper spp e Aniba canelilla e docagem molecular do 1-nitro-2-feniletano
(Universidade Federal do Pará, 2013-05-28) SILVA, Nayla Nunes dos Santos; ANDRADE, Eloisa Helena de Aguiar; http://lattes.cnpq.br/3827055876022373; MAIA, José Guilherme Soares; http://lattes.cnpq.br/1034534634988402
Currently, Alzheimer's disease (AD) is considered a significant public health problem worldwide and the major complication of the disease is the deficit of cholinergic neuron activity, a fact that can be reversed and/or mitigated by raising levels of the neurotransmitter acetylcholine (ACh). The most effective way to increase the available amount of acetylcholine is the inhibition of the acetylcholinesterase enzyme (AChE). In the search for new natural cholinesterasic inhibitors, the essential oils and major components of five aromatic plants occurring in the Amazon region were investigated using the AChE inhibition test by direct bioautography. The oils and major components were obtained from Aniba canelilla (1-nitro-2-phenylethane), P. aduncum (dillapiole), P. callosum (safrole), P. divaricatum (methyleugenol) and P. marginatum (safrole+3,4-methylenedioxipropiophenone). The oils of A. canelilla and P. aduncum showed enzyme inhibition zone in amounts of 0.01 ng and 1ng, respectively. The oil of P.marginatum showed weak activity (~ 100 ng) and the oils of P. callosum and P. divaricatum were inactive. Among the major constituents, who showed activity are the phenylpropanoids 1-nitro-2-phenylethane, isolated from the oil of A. canelilla, and safrole and elemicin, isolated from the oil of P. callosum, which inhibited the AChE in amounts of 0.01, 1000 to 1000 ng, respectively. The results indicate that the oil of A. canelilla and 1-nitro-2-phenylethane inhibited AChE in the same proportion as the pattern physostigmine. The molecular docking study was added to the experimental results, showing that the nitro group of 1-nitro-2-phenylethane can establish hydrogen bonds with the hydroxyl group of the serine residue existing in the catalytic AChE molecule, suggesting that the electronegative character of 1-nitro-2-phenylethane may be responsible for this strong chemical interaction.
Acesso aberto (Open Access)
Atividade antifúngica da nimesulida isolada ou em associação com a terbinafina contra fungos dermatófitos e seu provável mecanismo de ação in vitro
(Universidade Federal do Pará, 2015) MATOS, Rafaelle Fonseca de; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390
The dermatophytes has shown resistance to current antifungal agents such as Terbinafine, and this has led to research into new compounds as an alternative therapy. Thus, this study evaluated the action of non-steroidal antiinflamatory (NSAIDs) Nimesulide isolated and combined with Terbinafine against dermatophytes, dependence on Prostaglandins this mechanism of action and the effect of Nimesulide in the production of urease and fungal viability. The tests based were on CLSI, clinical and laboratory standards institute - reference method for microdilution test ground for antifungal susceptibility against filamentous fungi (M38-A standard). For clinical isolates of the species Trichophyton mentagrophytes, Trichophyton rubrum, Epidermophyton floccosum and Microsporum canis, the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) varied in the range> 400 ug / ml -> 0.112 g / ml. However, the results showed that the concentration of 0.002 mg / ml of Nimesulide was able to inhibit the growth of T. mentagrophytes ATCC 9533 and the concentration of 0.008 mg / ml was fungicidal for the same strain. Same values were find for Terbinafine on this strain. The inhibition of fungal growth by Nimesulide was reverse with application of exogenous prostaglandin E2 (PGE2). The urease test showed that T. mentagrophytes ATCC 9533 produces the enzyme, but no inhibition of fungal viability. In the nimesulide / Terbinafine association inhibition occurred in a ratio of 9: 1, or 0.0002 g / ml of Terbinafine and 0.0018 ug / ml of Nimesulide inhibited fungal growth but this result was the indifferent Fractional inhibition index. Nimesulide showed antifungal activity against dermatophytes in low concentrations, but other studies must be performed with the aid of molecular modeling to improve the targeting compound.
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/8514584872100128
The 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.
Acesso aberto (Open Access)
Avaliação da atividade dos extratos hidroetanólico de Chenopodium ambrosioides L. e de Eucalyptus alba Reinw ex Blume, frente a cepas de Mycobacterium sp
(Universidade Federal do Pará, 2014-10) VALÉRIO, Erika da Silva; BARBOSA, Wagner Luiz Ramos; http://lattes.cnpq.br/1372405563294070; TEIXEIRA, Francisco Martins; http://lattes.cnpq.br/7648303522085382
Chenopodium ambrosioides and Eucalyptus alba are species used in folk medicine for the treatment of tuberculosis and sputum. This study aimed to determine the physical-chemical, microbiological parameters, define phytochemical screening and evaluate antimycobacterial, cytotoxicity, immunomodulation, and toxicity in vivo activities of extracts and fractions. In physical-chemical and microbiological evaluation of C.ambrosioides and E. alba extracts, were found parameters in accordance with the specific literature for medicinal plants. The phytochemical screening of the extracts revealed the presence of saponins, steroids, triterpenoids, phenols and tannins, C. ambrosioides extract also showed proteins and amino acids, while the E. alba extract was positive for organic acids and lactones. The results of broth microdilution assay and microplate alamar blue assay showed moderates activities against the Mycobacterium fortuitum of E. alba extract and ethyl acetate fraction (FAcE) of E. alba; the chloroform fraction (FCl) of C.ambrosioides and the ethyl acetate fraction (FacEA) of E. alba were moderately active against the Mycobacterium tuberculosis. The cytotoxic activity, evaluated by MTT method, showed that the extracts did not reduce cell viability in the concentrations tested. In the immunomodulation assay, E. alba extract presented potential anti-inflammatory effect, by the methods of inhibition the production of NO and TNFα. No signs of acute oral toxicity of the extracts at a dose of 2500 mg/kg in mice were detected. These results suggest the potential antimycobacterial the FAcE of E. alba and immunomodulatory of E. alba extract and can serve as a resource for future studies, aimed at isolation of active compound and elucidation of their mechanisms of action.
Acesso aberto (Open Access)
Concentrações plasmáticas de primaquina e metemoglobinemia em pacientes com malária por Plasmodium vivax
(Universidade Federal do Pará, 2010) FERREIRA, Michelli Erica Souza; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098
The vivax malaria is a disease that effects around 40% of the world, to treat it, chloroquine (150 mg) and primaquine (15 mg). This is an 8-aminoquinoline with tissue schizonticide action. Among the adverse effects enhance the capacity to hemoglobin oxidation, dose-dependent, which is exacerbated in individuals with glucose-6-phosphate dehydrogenase deficiency. When considering the lack of studies concerning the methemoglobin levels and its correlation with primaquine concentrations plasma in patients with vivax malaria, is justified this study using as tools to monitor the plasma primaquine concentrations and its correlation with methemoglobin levels. In this sense, it was followed up clinically and laboratory findings of 20 patients with vivax malaria before (D0) and after three (D3), seven (D7) and fourteen (D14) days starting the treatment, as well as validation of the method for primaquine determination by high performance liquid chromatography (HPLC). Methemoglobinemia was evaluated using the method of Hegesh et al. (1970) and glucose-6-phosphate dehydrogenase by colorimetric method of Brewer et al. (1962 ). The methodology validated was demonstrated efficient for primaquine determination, whose average levels at D3, D7 and D14 were 227 ± 106 ng / mL, 191 ± 97 ng / mL and 160 ± 128 ng/mL. In the analysis according to gender was not observed differences significant in the drug levels in several days of study. The average methemoglobin levels in D0, D3, D7 and D14 were 1.15 ± 0.9%, 4.1 ± 2%, 5.7 ± 2% and 3 ± 1.4%, respectively. There was an increase in the methemoglobin level after drug administration, without difference by gender. There was not significant correlation between the methemoglobin levels and primaquine concentrations plasma in both sexes. The coefficients of Pearson correlation for males and females were 0.8296 and 0.8137, respectively. We observed impaired expression of the enzyme glucose-6-phosphate dehydrogenase in six male patients without differences between the methemoglobin levels and primaquine concentrations plasma, compared with patients with expression normal of the enzyme.
Acesso aberto (Open Access)
Concentrações plasmáticas de rifampicina em pacientes com tuberculose pulmonar
(Universidade Federal do Pará, 2017-12-01) BELEZA, Breno Kristoffer Uchôa; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098
Tuberculosis is an infectious-contagious disease that is still considered a major public health problem worldwide. Brazil is one of the 22 countries in the world responsible for 80% of the cases of the disease, and the highest incidence rates are observed in the North, Southeast and Northeast regions. The standard treatment regimen is composed of rifampicin, isoniazid, pyrazinamide and ethambutol. The clinical outcome is associated with the blood concentrations of these drugs after the use of therapeutic doses, however, despite the high incidence of the Brazilian disease, the concentrations of these drugs have not been evaluated in these patients, which is relevant mainly for rifampicin, given the high variability of concentrations in biological fluids after therapy. Therefore, a prospective case study was carried out to determine the concentrations of rifampicin by high performance liquid chromatography in patients with active tuberculosis treated in the city of Belém. Fifty patients were included in the study, however, there was a loss of clinical follow-up of 20 patients (40%), whose main reason was the abandonment of treatment. The social and demographic aspects of the others indicate a higher occurrence of the disease in males, low education, residents in the metropolitan area of Belém and in the productive age group. Rifampicin concentrations in the two treatment phases ranged from 0.6 μg / ml to 0.73 μg / ml. There was no significant difference in blood drug concentrations between treatment phases, however, rifampicin levels were significantly higher in women.
Acesso aberto (Open Access)
Desenvolvimento e caracterização tecnológica de micropartículas de arrabidaea chica (h & B) B. Verl. obtidas por spray dryer
(Universidade Federal do Pará, 2012-08) SAMPAIO, Rita de Cássia Almeida; BARBOSA, Wagner Luiz Ramos; http://lattes.cnpq.br/1372405563294070; SILVA JÚNIOR, José Otávio Carréra; http://lattes.cnpq.br/4437885351749994
This work aimed the technological development of particulate dosage forms obtained from extraction solution (tincture) from aerial parts of Arrabidea chica (Pariri), using the spray drying. We investigated the influence of processing aids (maltodextrin and arabic gum, alone and in a mixer) in drying performance and product properties. A. chica tincture was concentrated on a rotary evaporator to obtain the concentrated extract (CE) which was added to the processing aids and subjected to spray drying. The drying process was assessed through determination of product recovery and thermal efficiency. Microparticles (ES) were evaluated for residual moisture, water activity, average particle diameter, bulk density, packing density and flow properties, thermal profile and IR spectroscopy. The chemical monitoring was performed by UV-vis spectrophotometer, using chemical marker flavonoids (Ft), polyphenols (Pt) and total tannins (Tt) in the A. chica. The antioxidant activity of the product was evaluated by DPPH and chemiluminescence. The moisture content of the ES had their values in the range 2.77 to 4.69% being within the specified. The water activity values were below 0.2, which supports the physical and chemical stability and microbiological of dried products. The percentage of degradation of chemical markers in ES regard to CE was in the range 24-46% for Ft, 48-56% for Pt and 53-72% to Tt, which may be associated with thermal degradation and oxidation of the same compounds. In TLC analysis, tincture, CE and ES showing the luteolin and kaempferol patterns indicate that the drying process does not cause the loss of these compounds. The particle size distribution shows that the ES showed an average diameter of about 10 μm and the particles had a spherical morphology and with some rough surface. The flowability indices and accommodation of the powders obtained results are typical of powders with low flowability and compressibility characteristics. The antioxidant activity of ES presented values between 32.17 to 44.53 mg / mL. In the colorimetric analysis, the parameters proved the yellowish-red color. The recovery of product was in the range 60-65% and the thermal efficiency values were between 36% and 39%. Analyses of infrared spectroscopy and thermal analysis proved important tools in the physico-chemical characterization and quality control systems microparticulate obtained.
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/6710783324317390
Inflammation 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.
Acesso aberto (Open Access)
Efeitos do antioxidante tempol nas alterações bioquímicas e estruturais induzidas pela metaloproteinase de matriz 2 no coração
(Universidade Federal do Pará, 2020-09-11) GONÇALVES, Pricila Rodrigues; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390; https://orcid.org/ 0000-0002-3328-5650; PRADO, Alejandro Ferraz do; http://lattes.cnpq.br/7016475842644161; https://orcid.org/ 0000-0001-7495-9837
MMP-2 expression is elevated in many cardiovascular pathologies such as myocardial infarction and heart failure, where tissue remodeling and inflammatory responses are disturbed. Changes in ECM homeostasis can lead to cardiac dysfunction. The most analyzed MMPs in relation to cardiac dysfunction are MMP 2 and MMP-9. ROS inhibitors, as antioxidants, have been shown to reduce the expression of MMP-2 in vascular tissue. Thus, antioxidants with Tempol have great potential to act on these mechanisms. Therefore, we evaluated the activity and purity of rhMMP-2 using the zymogram and SDS-PAGE silver-stained method. The animals were divided into 4 treatment groups. Group 1: received 0.9% saline; group 2: Tempol 18 mg / kg / v.o; group 3: MMP-2 150 ng / kg / i.p; group 4: Tempol 18 mg / kg / v.o + MMP-2 150 ng / kg / i.p; for 4 weeks. At the end of the treatment, the heart was collected for quantification of collagen, quantification of ROS by fluorescence microscopy and immunofluorescence for TNFα and TGF-β. After the analysis, our results showed that rhMMP-2 was pure and active and that there was no difference in the average weight of the animals (P> 0.05). In the group treated withrhMMP-2 and Tempol, there was a decrease in the heart weight / body weight ratio, compared to the control group (P <0.05). Tempol was able to decrease collagen in the heart of animals treated with rhMMP 2. We also saw rhMMP-2 increased ROS in the heart, which was prevented by Tempol. RhMMP-2 also led to an increase in TNF-α and TGF-β in the heart, however TGF-β was reduced by Tempol. In conclusion, rhMMP-2 infusion increased cardiac ROS, which can lead to oxidative stress, with a consequent increase in TNF-α and TGF-β, which can result in a heart with a pro-fibrotic and inflammatory profile. However, Tempol was able to reduce interstitial collagen, inhibit the increase in ROS, TNF-α, TGF-β and increase catalase in the heart. Having Tempol, the potential to inhibit factors that lead to oxidative stress, inflammation and cardiac fibrosis.
Acesso aberto (Open Access)
Efeitos do quelante de ferro, a deferoxamina, sobre as alterações oxidativas e cognitivas induzidas pela dapsona, em modelo animal
(Universidade Federal do Pará, 2020-11-17) MENDES, Paulo Fernando Santos; MAIA, Cristiane do Socorro Ferraz; http://lattes.cnpq.br/4835820645258101; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390; https://orcid.org/ 0000-0002-3328-5650
Dapsone (DDS) is an antibiotic that works by inhibiting folate synthesis, showing good bacteriostatic action. However, it can lead to severe adverse events such as neurological disorders, methemoglobinemia and hemolysis. These hematological disorders lead to the alteration of iron homeostasis and thereby increase the formation of ROS that can lead to cellular and tissue damage. This change plays an important role in neurodegenerative diseases, whether as a causative and / or intensifying agent in these diseases. In this context, we used an iron chelator, deferoxamine (DFX), to evaluate its effects on the formation of ROS triggered by the increase in free iron induced by the use of DDS. For this, the alteration of iron homeostasis was induced in Swiss mice, using DDS, followed by the administration of DFX. After that, oxidative stress parameters were measured in the hippocampus and plasma, in addition to the measurement of iron levels. Our results showed that DDS decreased TEAC and that DFX treatment was restored. In addition, DDS decreased GSH and DFX treatment was restored. It increased the LPO and the treatment with DFX reduced this effect, increased the concentration of iron and that was reversed by the treatment with DFX. Additionally, the animals were submitted to the Morris water maze, where our results showed that animals treated with DDS showed a reduction in mnemonic capacity and that treatment with DFX was able to inhibit loss. These results suggest that the use of iron chelators may be an alternative to reduce the effects of iron accumulation on the nervous system observed in neurodegenerative diseases.
Acesso aberto (Open Access)
Efeitos no comportamento motor após intoxicação subcrônica de metilmercúrio na presença de etanol (padrão binge) em ratas adolescentes à fase adulta
(Universidade Federal do Pará, 2015-11-06) OLIVEIRA, Aline do Nascimento de; MAIA, Cristiane do Socorro Ferraz; http://lattes.cnpq.br/4835820645258101
Exposure to methylmercury through the contaminated seafood diet, concomitant abusive alcohol intake, in binge pattern, is quite common in gold mining communities of gold extraction, especially in the Amazon. The association between these two neurotoxicantes is also evident among adolescent women and creates the need to understand its effects on the central nervous system, especially in motor coordination, balance and spontaneous locomotion, because the studies are advanced only for the effects of exposure in isolation. Therefore this study aims to evaluate the effects on motor behavior resulting of subchronic exposure to methylmercury in the presence of alcohol, in binge pattern, in adolescents female rats until early adulthood (37-72 postnatal day), through behavioral motors tests, like Open Field, Pole Test, Rotarod and Beam Walking Test. The testing occurred 24 hours after the last intoxication of rats, which received methylmercury (0.04 mg / kg / day) for 35 days, concomitant with alcohol (3g / kg / day), 3 intermittent days, 1 time per week (binge), totaling 5 binges. The results showed a decrease in spontaneous locomotion in Open Field test through the parameters of the total distance traveled and number of rearing. In the Pole test was increased fall time, evidencing the bradykinesia. In the Rotarod there was a decrease in latency in the first three exhibitions, as well as Beam Walking Test was increased latency and number of slips, especially in thinner beams, showing that subchronic exposure to methylmercury in the presence of alcohol, in the binge, in adolescent female rats was able to produce behavioral damages related to coordinating motor, balance and spontaneous locomotor activity.
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/0458080121943649
Parahancornia 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.
Acesso aberto (Open Access)
Estudo teórico do complexo cefoxitina-proteína 5 de ligação à penicilina da Escherichia Coli por dinâmica molecular com método híbrido de mecânica quântica/ mecânica molecular
(Universidade Federal do Pará, 2014-12-12) SILVA, Thaís Boulhosa Barros da; BARROS, Carlos Augusto Lima; http://lattes.cnpq.br/8902921733540173; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390
The Penicillin Binding Proteins (PBPs) are important for the development of new drugs against bacterial infections biological targets. This study was aimed to understand the interaction between the protein and cefoxitin 5 Penicillin-Binding (PBP5) of Escherichia coli (deposited in the PDB under the code 3MZE) through simulation Molecular Dynamics (MD), using the approach hybrid quantum molecular mechanics (QM/MM) and mechanical. As well as develop a prototype to evaluate, through computer simulation, the susceptibility of Gram negative bacteria against antibiotics. The analysis of antimicrobial susceptibility to antibiotics tested has shown that this strain of E. coli ATCC 8739 was sensitive to 5 antimicrobials study. The strain of E. coli derived from the clinical isolate was resistant to ciprofloxacin 5 μg and gentamicin 10 μg, intermediate sensitivity to cefepime 30 μg and ceftazidime 30 μg, and sensitivity to cefoxitina 30 μg. The difference in susceptibility of E. coli strain ATCC 8739 and strain of E. coli isolated from a clinical can show a molecular immunological memory of the bacteria. We observed no production of β-lactamases by the strain of E. coli derived from clinical isolate, suggested because no observed difference in antimicrobial susceptibility with respect to the presence or absence of EDTA on the disks containing the antibiotics. The analysis has revealed that protonation of the deprotonated His146, His151, His216 and His320 residues. The stabilization of the complex was studied after 0,6 ns of MD simulation. Moreover, a decomposition analysis in terms of energy was performed to determine the contributions of individual amino acid residues for protein-ligand interactions. The results revealed that cefoxitin has a strong interaction with Lis44, Lis210, Ser41, Gli212, His213, Glu246 residue, apart from water, which are important for stabilizing cefoxitin-PBP5 complex. The electrostatic potential map Molecular cefoxitin revealed a highly electrophilic center corresponding to the β-lactam ring, which promotes hydroxyl attack nuceofílico the serine residue of the E. coli PBP5 active site region. These results can give support the planning of new more selective and effective drugs to control bacterial infections. The experimental results were statistically consistent with the theoretical results thus this work can be used as a prototype for computing theoretical evaluate the antimicrobial susceptibility to Gram negative bacteria. This study may find applications in future planning and development of new and potent compounds with antimicrobial activity. Mainly in attempts to modify an inhibitor, particularly of the cephalosporin class in order to improve its selectivity and its activity.
Acesso aberto (Open Access)
Estudo teórico do mecanismo redox de derivados quinolínicos na atividade antimalárica
(Universidade Federal do Pará, 2010) SCALERCIO, Sarah Raphaella Rocha de Azevedo; BORGES, Rosivaldo dos Santos; http://lattes.cnpq.br/4783661132100859
Malaria is a serious public health problem worldwide, causing socioeconomic deficits and contributing to subdevelopment in affected countries. In this context is important to study electronic properties, quinoline derivatives antioxidant potential and antimalarial activity relationship to design effective antimalariais prototypes. In this dissertation are used molecular modeling methods to study antioxidant and antimalarial structure-activity relationships selecting moieties and eletronic and conformacional parameters to improve farmacological activity and decrease derivatives toxicity. The HOMO and PI values analysis indicates that imino-tautomer is, probably, better antioxidant than amino-tautomer. It also observed that tautomers equilibrium is favored to amino-quinoline in the gas phase, and in water and chloroform using PCM method, with energy barriers values to 10.78 Kcal/mol, 21.65 Kcal/mol and 22.04 Kcal/mol, respectively. Then, may be noted that in quinoline analogues derivatives the electron-donor groups decrease the ionization potential, as exemple of the amino group at 8-position replaced by an alkylamine group. In 4- 8- amino-quinoline derivatives association observed that presence of quinoline moiety second nitrogen decrease its antioxidant activity, except in the 5-position, representing the most prominent group in the reduction of ionization potential and probably high antioxidant activity.
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/0458080121943649
The 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.
Acesso aberto (Open Access)
Estudos farmacognósticos, fitoquímicos e atividade antileishmania de espécies Geissospermum (Apocynaceae)
(Universidade Federal do Pará, 2016-11-07) SILVA, João Victor da Silva e; MARINHO, Andrey Moacir do Rosario; http://lattes.cnpq.br/2511998363000599; DOLABELA, Maria Fâni; http://lattes.cnpq.br/0458080121943649
This study aimed to perform pharmacognostic and phytochemical studies, and assess antileishmanial activity and cytotoxicity of Geissospermum vellosii Allemão and Geissospermum sericeum Miers. The pharmacognostic study was carried out as described in the Brazilian Pharmacopoeia, 2010. The ethanol extracts (GVEE and GSEE) were obtained by exhaustive maceration with ethanol (96 ° GL), followed by concentration in rotaevaporator. The ethanol extract was fractionated using two methods: extraction under reflux (fractions of different polarities) and acid-base partition (neutral and alkaloid fractions). The alkaloid fractions (GVAF and GSAF) were fractionated on a chromatographic column with Sephadex LH-20 gel, and the resulting subfractions were analyzed on TLC, and reveled through Dragendorff reagent and ultraviolet (365 nm). The F6GVAF and F6GSAF subfractions, with alkaloids detected and good yield, were subjected to semi-preparative HPLC-DAD, and spectrophotometric methods. For evaluating the antileishmanial activity, promastigote forms of Leishmania amazonensis at a concentration of 5 x 106 parasites/100μL were treated with the samples at different concentrations for 24, 48 and 72h. The analysis was done adding [3- (4,5-dimethylthiazol-2-yl) -2,5- diphenyltetrazolium bromide (MTT) to the samples in an ELISA reader at 490 nm. Cytotoxicity was assessed through cell viability assay with MTT in differentiated THP- 1 cells and HepG2. As a selection criteria, the selectivity index (IS) was calculated as the ratio between the cytotoxic concentration 50% in cell lines, and the inhibitory concentration 50% found for protozoa, considering as promising values ≥ 10. The plant powder was classified as thick (G. vellosii), and very thick (G. sericeum), low density, with pH 4.94 (G. vellosii) and 6.47 (G. sericeum), negative to saponins, with ash and moisture within the parameters established by the Brazilian Pharmacopoeia V. In the phytochemical study, we suggest the isolation of an indole alkaloid (F3F6FAGV) and a β-carbolinic (flavopereirine) from both species. The fractionation of GVEE and GSEE resulted in more cytotoxic subfractions, but the exposure time and refractionation reduced this effect. In the antipromatigota assay, all samples were active, and the fractionation increased the activity. The flavopereirine presented time-dependent activity greater than amphotericin B. However, the flavopereirine in association with indole alkaloid and/or amphotericin B reduced the selectivity of this metabolite. The extracts fractionation increases the selectivity index, and the selectivity of flavopereirin is high (SI = 4893.3). Therefore, the isolation of flavopereirine contributes to reduce cytotoxicity and increase selectivity, showing itself as a promising antileishmanial agent.
Acesso aberto (Open Access)
Exposição ao MEHG provoca dano na medula espinhal: percepções a partir da análise proteômica e estresse oxidativo
(Universidade Federal do Pará, 2020-08-27) EIRÓ, Luciana Guimarães; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468; https://orcid.org/ 0000-0003-1486-4013
Methylmercury (MeHg) is considered by the World Health Organization as one of the chemicals of greatest public health concern. Thus, knowing the susceptibility of central nervous system regions and the absence of evidence about the effects on the spinal cord, this study aimed to investigate proteomic and biochemical changes in the spinal cord after MeHg long-term exposure at low doses. For this, male Wistar rats were exposed to a dose of 0.04 mg/kg/day by for 60 days. After that, the proteome was identified with subsequent overrepresentation analysis (ORA). For the oxidative biochemistry, the antioxidant (ACAP, TEAC, GSH) and pro-oxidants (LPO and nitrite ions) parameters were evaluated. The proteomic analysis showed several altered proteins that participate in biological processes, cellular components, and molecular functions. There was an increase in total mercury (Hg) levels in the spinal cord, as well as an increase in LPO and nitrite ions and a reduction in ACAP, TEAC and GSH. Therefore, exposure to low doses of MeHg can trigger oxidative stress associated with changes in the proteomic profile.
Acesso aberto (Open Access)
Extratos de Pyrostegia venusta: caracterização físico-química, capacidade imunomoduladora e prevenção da formação do biofilme dental
(Universidade Federal do Pará, 2013-09-27) SOUSA, Mayara Brito de; SILVA JÚNIOR, José Otávio Carréra; http://lattes.cnpq.br/4437885351749994; TEIXEIRA, Francisco Martins; http://lattes.cnpq.br/7648303522085382
Pyrostegia venusta is a climbing plant popularly known as “flor-de-São-João”. In traditional medicine is used to treat various diseases. Within the scientific literature various bioactive compounds have been isolated and some important biological activities as antimicrobial e immunomodulatory activities have been attributed to this specie. Caries and periodontal disease are the most prevalent oral pathologies among Brazilian population and dental biofilm is the main etiological factor of these diseases. Oral candidiasis is an infection caused by species of the yeast Candida which in some cases may behave as opportunistic pathogens. The aim of this study was to evaluate the physical, chemical and biological aspects of Pyrostegia venusta and its potential in the prevention of the main oral diseases. It was evaluated the cytotoxicity of the crude extract and its fractions in peripheral blood mononuclear cells and murine macrophages. The immunomodulatory activity of the crude extract and its fractions was verified through the dosage of nitric oxide (NO) production by macrophages murines stimulated with lipopolysaccharide (LPS). Through broth microdilution assay it was determined the minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC) and minimal fungicidal concentration (MFC) of the crude extract, fractions and isolated compounds. It was also evaluated the inhibition of Streptococcus mutans adherence to a glass cover slip, pH reduction capacity and the effect on germ-tube formation and budding of Candida albicans of the crude extract and its fractions. Pyrostegia venusta was not cytotoxic at low concentrations. NO production was inhibited by ethyl acetate and n-butanol fractions. Crude extract, fractions and isolated compounds have antimicrobial activity against Streptococcus mutans, Streptococcus mitis, Streptococcus oralis and Candida albicans; they also inhibited the adherence and were able to reduce the pH. Crude extract and hexane, ethyl acetate and n-butanol fractions inhibited the germ-tube formation and budding of Candida albicans. Pyrostegia venusta can be an alternative in prevention and treatment of the main oral diseases. However, other studies are necessary before it is considered as a promising specie.
Acesso aberto (Open Access)
Investigação fitoquímica e atividade biológica das cascas de Luehea speciosa willd
(Universidade Federal do Pará, 2017-12-21) NASCIMENTO, Maisa Carmen Batista do; BARBOSA, Wagner Luiz Ramos; http://lattes.cnpq.br/1372405563294070
The barks of Luehea speciosa, family Malvaceae, are used in traditional medicine to treat dysentery, rheumatism, tumors, bronchitis, skin wounds, weight loss and others diseases. However, studies give little information about the species in the literature. Thus, it is of great interest to investigate its chemical constitution and biological activities, since the scientific proof of its activity can promote, in the future, a therapeutic alternative. The present study analyzed the chemical constitution of the dry crude extract (EBS) and hexane (FHX), dichloromethane (FDM), ethyl acetate (AED) and methanolic (FME) fractions of the species by high-performance liquid chromatography (HPLC) with tandem mass spectrometric - LC/MS, as well as its antioxidant activities by bioautography and cytotoxic assays, in vitro, against HELA, HEP-2 and VERO tumor cell lines. The samples showed antioxidant activity, being the fractions FDM and AED results more relevant. The EBS and fractions demonstrated cytotoxicity on all cell lines, however the FDM fraction had greater cytotoxic activity against tumor cells. In the LC/MS analyzes, were detected phenolic compounds and suggestive characteristics of chicoric acid presence through m/z = 148, as in the UV spectrum. These results demonstrate that this species has antioxidant activity and suggest its cytotoxicity against tumor cells, being a promising species for future studies.