Navegando por Orientadores "MONTEIRO, Marta Chagas"

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Acesso aberto (Open Access)
Alterações oxidativas e inflamatórias induzidas pela dapsona no sangue e no córtex pré-frontal de camundongos: efeitos do ácido alfa-lipóico
(Universidade Federal do Pará, 2018-12-14) GOMES, Bruno Alexandre Quadros; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390
Dapsone (DDS), a drug used in leprosy multidrug therapy, can cause many adverse reactions and intoxications, inducing the generation of reactive oxygen species (ROS) and imbalance in the redox state, increase methemoglobin (MetHb) formation, hemolysis and release of heme and iron free, which may interfere with redox homeostasis in more vulnerable regions, such as prefrontal cortex (PFC), causing neurotoxicity and even neuroinflammation. In this sense, antioxidant compounds with chelating properties such as α-lipoic acid (ALA) may play a key role in combating or preventing these alterations. Thus, this work aims to evaluate the effect of DDS on MetHb formation, peripheral oxidative stress, and oxidative changes and neuroinflammation in PFC, as well as, effects of ALA. For this, was induced MetHb formation in Swiss mice with DDS 40mg/kg ip for 5 days. Two hours after DDS administration, ALA was given at two concentrations (12.5 and 25 mg/kg). Besides MetHb percentage, total equivalent antioxidant capacity (TEAC), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) thiobarbituric acid reactive substances (TBARS), and iron concentrations in blood and PFC were evaluated, as well as, IL-1β, IL-17, and IL-4 cytokine concentrations, and de F4/80+, GFAP, and BDNF expression in PFC. Our results show that DDS induces the MetHb formation in red blood cells of mice, however, ALA was able to prevent or reverse the oxidation of hemoglobin induced by DDS at two used concentrationns. DDS reduced antioxidant capacity (TEAC) in plasma and red blood cells; decreased erythrocyte GSH, CAT, and SOD; and increased TBARS and plasma iron; however, ALA at two concentrations increased or reestablished TEAC in plasma and red blood cells at baseline levels. In addition to increasing or reestablishing GSH levels, SOD, and CAT in red blood cells, and decreased TBARS and iron levels, mainly in euthanized animals 4h after treatment. Curiously ALA 50mg/kg increased plasma iron concentrations. The treatment with DDS 40mg/kg also reduced TEAC, GSH, SOD e CAT in the PFC of the mice and increased TBARS and iron, characterizing oxidative stress, mainly in euthanized animals in 24h after treatment. Treatment with ALA increased or restored TEAC and GSH; and increased SOD and CAT in 12,5mg/kg concentration in euthanized animals 4h after treatment, as well as reducing TBARS levels and decreasing or preventing iron overload, mainly in euthanized animals 24h after treatment. DDS also promoting microglial and astrocyte activation in PFC, through F4/80+ e GFAP expression., with increased IL-1β and IL-4 production, and BDNF reduction, on the other hand, ALA 25mg/kg reduced GFAP and IL-1β expression, besides increased BDNF, suggesting that DDS also can cause neuroinflammation, and ALA presents antioxidant and anti-inflammatory properties against toxicity caused by DDS. These results suggest that ALA is promising and plays an important role in the prevention and/or formation of MetHb, reestablishment of redox balance and iron concentrations in both blood and PFC. Thus, ALA may be a usefull adjuvant therapy in DDS-induced toxicity, with lower toxicity and increasing adherence to treatment of leprosy patients.
Acesso aberto (Open Access)
Atividade antibacteriana, antioxidante e citotóxica in vitro do extrato etanólico da entrecasca da planta Ouratea hexasperma (EEEOH) (A. St-Hil.) Baill var. Planchonii Engl
(Universidade Federal do Pará, 2015-09-17) COSTA, Glauber Vilhena da; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390
Ouratea hexasperma (Ochnacea), popularly known as "cerrado barbatimão" is a very common plant in the brazilian cerrado region and has been used for the treatment of microbial infections and inflammation. Therefore, this study aimed to evaluate the antioxidant activities, quantifying total flavonoid content (TFT), antibacterial and cytotoxicity of ethanol extract of the bark of Ouratea hexasperma (EEBOH) as well as perform their phytochemical characterization. The plant was collected in the state of Amapá, and then was held extraction of dry bark through the cold maceration with 96% ethanol solution in a 2: 8 (w/v) for 1 day, forming the EEBOH. The phytochemical characterization was performed by testing chromatic/precipitation tube and flavonoid content was measured by assay complexation with aluminum using quercetin as standard (40-0,62μg/mL), and the total antioxidant capacity by the spectrophotometric method discoloration radical ABTS•+ (2,2'azino-bis-3-etilbenzotiazolin 6-sulfonic acid) - TEAC. The antimicrobial activity of EEBOH was tested against gram-positive and gram-negative bacteria, using the microdilution techniques broth with staining by resazurin, to determine the Minimum Inhibitory Concentration (MIC), and grown in petri dish with subsequent count of colony forming units (CFU) for obtaining the Minimum Bactericidal Concentration (MBC). The evaluation of the cytotoxicity of EEEOH human peripheral blood leukocytes. Mononuclear peripheral blood cells incubated with different concentrations of the extract and without stimulation (negative control). The cytotoxicity of EEEOH were tested using human peripheral blood leukocyte, mononuclear cells, with different extract concentrations and without stimulation (negative control), and incubated and maintained at 37 ° C, 98% humidity and 5% CO2 for 24 hours, NO and MDA were read in an ELISA spectrophotometer and different optical readings. The primary EEBOH phytochemical analysis showed the presence of tannins, saponins and flavonoids. The TFT in the extract was 1467 ± 264μg equivalents quercetin/g EEBOH. The antioxidant capacity by TEAC method showed high antioxidant activity, with no difference in antioxidant capacity (TEAC) between those concentrations of the extract. The EEBOH showed good antibacterial activity, mainly against gram-positive bacteria. The cytotoxicity was obtained by linear regression concentration able to kill 50% of cells (CC 50%) whose amount was 2231,5mg/mL, confirming that the crude extract has low cytotoxicity against human leukocytes, under the conditions tested. In the production of NO and MDA it found that the EEOC was not able to induce NO production of the concentrations tested. As well, no increase MDA of concentration induces changes when compared to the negative control (RPMI), confirming the low in vitro cytotoxicity of the extract. Statistical analyzes were performed by ANOVA one way and Turkey. In concluded that the EEBOH have antibacterial, antioxidant and low cytotoxicity.
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)
Atividade antimicrobiana do óleo essencial de Piper aduncum L. e seu componente, dilapiol, frente a Staphylococcus spp. multirresistentes
(Universidade Federal do Pará, 2012-08-31) BRAZÃO, Maria Angélica Bolini; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390
The essential oil of Piper aduncum (EPO) and its main component, the dilapiol (76.5%), were evaluated for antibacterial activity against different strains of Staphylococcus spp. ATCC and multiresistant. For testing the antibacterial activity of EPO and dilapiol were determined Minimum Inhibitory Concentration (MIC) and minimum bactericidal concentration (MBC), the technique of microdilution and by counting Colony Forming Units (CFU) using concentrations of 250, 500 , 750 and 1000 μg/ml of EPO and concentrations of 100 and 1000 μg/ml dilapiol. The bacterial inoculum used was adjusted to 1x104 range from 0.5 Mc Farland. As a negative control inoculum was used along with Tween 20, solubilising the essential oil and dilapiol, and as positive control we used the chloramphenicol 0.05 mg/mL. These compounds were tested against strains of S. aureus ATCC 25923, S. epidermidis ATCC 12228, MRSA hospital, and S.epidermidis, S. lentus multiresistant nosocomial. The results showed that the EPO showed the MIC 90% of 500 μg/mL and MBC of 1000 μg/mL against S. aureus ATCC 25923, whose concentration of 500 μg/mL was able to inhibit 60% of bacterial growth. The strain MRSA, the EPO showed a small inhibition (10%) at a concentration of 750 μg/mL, being obtained in the MIC90% 1000 μg/mL. In S. epidermidis ATCC 12228, the OEPA showed antimicrobial activity with MIC90% at 500 μg/mL and MBC at 750 μg/mL. For the strain S. epidermidis multiresistant, the PEO was able to inhibit only 35% growth of this strain at a concentration of 750 μg/mL, but the value obtained in the MIC90% 1000 mg/mL. As for dilapiol, the compound showed antimicrobial activity against a strain of S. aureus ATCC 25923 at a concentration of 1000 μg/mL, 100% growth inhibiting (CBM). On the other hand, had no antimicrobial effect on MRSA strain nor S. lentus multiresistant. Furthermore, the dilapiol inhibited only 20% of the growth of S. epidermidis ATCC 12228 and S. epidermidis multiresistant concentration of 1000 μg/mL. Thus, the data show a moderate antibacterial activity of the essential oil, and the dilapiol showed weak in vitro antimicrobial activity.
Acesso aberto (Open Access)
Atividade antimicrobiana, antioxidante e imunomoduladora de Agaricus brasiliensis e Ilex paraguariensis in vitro e em modelo de sepse murino
(Universidade Federal do Pará, 2016-09-15) NAVEGANTES, Kely Campos; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390
Sepsis is an organ dysfunction caused by a dysregulated immune response to an infection, the initial therapeutic approach to sepsis are broad spectrum antimicrobials, which is not sufficient for control of infection, requiring association with other therapies. Thus, Ilex paraguariensis where to be a potent antimicrobial, antioxidant and Agaricus brasiliensis has immunomodulatory properties could be a new source of therapy. Thus, this study aimed to evaluate the antimicrobial effect, antioxidant and immunomodulatory in vitro and in vivo of the extracts. Therefore, in this study, we evaluated the in vitro antimicrobial activity of aqueous extracts from A.brasiliensis and I. paraguariensis against Staphylococcus aureus and Escherichia coli by the method of microdilution and by spectophotometry for determination of minimum inhibitory concentration and cultivation technique on petri dish for minimum bactericidal concentration, cytotoxicity in macrophages was evaluated, nitric oxide (NO) production, proliferation, phagocytosis, equivalent antioxidant capacity to Trolox (TEAC) and determination of the total antioxidant activity by capturing the free radical and reactive species production oxygen (ROS). In the swiss mice with induced sepsis were pretreated with aqueous extracts of A.brasiliensis and I. paraguariensis, after 12 and 24 hours collected their samples and evaluated the survival, leukocyte migration, hemogram, bacterial load, NO production, malondialdehyde (MDA), TEAC and ex vivo we evaluated phagocytic capacity and release of ROS. The A.brasiliensis showed no antimicrobial activity in vitro, remained viable cells reduced the phagocytic capacity, increased NO, but in the presence of LPS reduced, showed proliferative effect, but in the presence of mitogen had antiproliferative effect and has a strong antioxidant activity and capacity to sequester radicals in vitro. I.paraguariensis presented antimicrobial activity as well as cytotoxic effect induced phagocytic capacity increased NO, but in the presence of LPS reduced, had proliferative effect, antioxidant activity and capacity to sequester radicals in vitro. In vivo model of sepsis, both increased the survival of animals, A.brasiliensis reduced leukocyte influx while Ilex increased, only A.brasiliensis had hemogram similar to sham, both extracts reduced bacterial load and levels decreased NO, MDA and increased antioxidant levels in the tissues, in addition, both reduced the production of both extracts present ERO. Although excellent in vitro results, the aqueous extract from A.brasiliensis was found to be most promising as an adjuvant therapy in sepsis that I. paraguariensis due to its high antimicrobial activity, antioxidant and anti-inflammatory in vivo.
Acesso aberto (Open Access)
Atividade imunomoduladora e antioxidante da saliva do Aedes aegypti em modelo de sepse
(Universidade Federal do Pará, 2017-07-04) GOMES, Rafaelli de Souza; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390
Sepsis is an organ dysfunction caused by a dysregulated immune response to an infection, the initial therapeutic approach to sepsis are broad spectrum antimicrobials, which is not sufficient for control of infection, requiring association with other therapies focused in the interruption of the inflammatory response chain, provided by the pathogens. In this way, the Aedes Aegypti’s saliva presents immunomodulary features, with a potential pro inflammatory cytokine inhibition, as well as the presence of nitric oxide peptides activators. Therefore, it would be a great interest to search the saliva’s immunomodulator effect in animal model sepses. In this regards, mices were pre treated with Aedes aegypti saliva, and sepsis was induced by the cecal ligation and puncture. After 12 and 24 hours, the samples were collected, and evaluated the survival rate, bacteria level, leukocyte migration, and oxidative parameters (NO, EROs, MDA e TEAC). The saliva improved the animal prognostic, increasing the survival rate and weight. Furthermore, decreased the bacterial levels and increased the influx of monocytes. The saliva, in addition, presented antioxidant effects by reducing production of the reatives species, and increasing the antioxidant capacity, other than decrease the lipid peroxidation. Thus, the saliva was capable to inhibit damages caused by sepsis in animals in vivo, improving its prognostic.
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/6710783324317390
The 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.
Acesso aberto (Open Access)
Avaliação do efeito da fração lipídica extraída de Agaricus brasiliensis antioxidante e imunomoduladora in vitro e em modelo de sepse letal em murino
(Universidade Federal do Pará, 2021-01) LIMA, Kely Campos Navegantes; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390; https://orcid.org/0000-0002-3328-5650
Sepsis is defined as a potentially fatal organ dysfunction caused by a dysregulated host immune response to an infection. During sepsis, dysregulation of the host response occurs with the excessive release of pro-inflammatory mediators, generation of reactive species with depletion of antioxidant defenses and cellular damage. As a result, the patient develops organ dysfunction. In this context, our group proposes the A.brasiliensis Lipid Fraction (FLAb) as a possible therapy for sepsis considering its immunomodulatory and systemic antioxidant activity in a murine sepsis model. Thus, the present study aimed to evaluate the activity of FLAb isolated in vitro and to evaluate the effect of treatment with FLAb alone or associated with the antibiotic ertapenem (F-Erta) on coagulation, antioxidant and immunomodulatory parameters in the lethal sepsis model in murine. For this, FLAb was kindly provided by Dr. Herta Dalla- Santa from UNICENTRO. In the present study, the antioxidant capacity of different concentrations of FLAb (1.25 and 5 μg/mL) was evaluated and in a RAW 264.7-Luc macrophage cell line, cytotoxicity, phagocytic capacity, nitric oxide, NF-κB activity and cytokines TNF-α and IL-6 were evaluated.The survival rates were analyzed 7 days in a model of CLP sepsis in swiss albino mice (Mus musculus), and treated with CLP+Salt (0.9%), CLP+FLAb (0.2mg/Kg), CLP+F-erta (0.2mg) /Kg; 30mg/Kg). For evaluation of on coagulation, antioxidant and immunomodulatory parameters, the mice were treated by 6 and/or 24h after CLP. In vitro, FLAb show antioxidant and anti-inflammatory activity in both concentrations. In vivo, all CLP+Salt animals died within a maximum of 48 hours while the FLAb and F-Erta treated groups survived the 7 days. During this period, clinical parameters of these animals were evaluated, the septic animals treated with saline showed piloerection, with little active level of consciousness and most of the time they were stopped in the cage, some of them had ocular secretion. In addition, animals treated with saline showed significant weight loss, reduced water and feed consumption resulting in death. The FLAb and F-Erta groups were active, with normal appearance, with normal breathing and heart rate, in addition to consuming water and food within normal limits. In the inflammatory site, peritoneal cavity, the treatment with FLAb showed an anti-inflammatory effect, decreased reactive oxygen species (ROS) and increased GSH antioxidant activity and protected from cell damage, maintaining neutrophil recruitment and nitric oxide levels (NO), reducing the bacterial load. Regarding coagulation parameters (platelet count, tp and ttpa), treatment with FLAb and F-Erta eliminated the bacterial load and protected the animals from tissue damage. In the liver, 6 hours after CLP the treatment with FLAb and F-ERTA was observed in the biochemical parameters protective effect, in addition, it presented immunomodulatory, antimicrobial and antioxidant activity preventing liver damage. In the parameters evaluated in the heart, the treatment with FLAb and F-ERTA after CLP protected the animals from cardiac damage through immunomodulatory, antimicrobial and antioxidant activity. In this sense, FLAb alone showed promise as a treatment and/or adjunct in sepsis, in addition to preventing organic dysfunction in septic animals.
Acesso aberto (Open Access)
Avaliação do efeito imunomodulador da β-lapachona em modelo de sepse e in vitro
(Universidade Federal do Pará, 2018-06-29) OLIVEIRA, Ana Lígia de Brito; BRAGA, Alaide; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390; https://orcid.org/ 0000-0002-3328-5650
Sepsis is a systemic inflammatory response resulting from an infection and failure of the host immune response. Despite the current treatments, sepsis remains one of the main causes of death in ICU. Thus, it is necessary to discover new therapies developed to control the infection. Β-lapachone is an ortho-naphthoquinone obtained from the bark of Tabebuia avellanedae known for its antimicrobial and anti-inflammatory activity through immunomodulation. In this study, the effect of β-lapachone on polymicrobial infection induced by ligature and cecal perforation (CLP) was evaluated. Swiss mice were divided into 4 pre and post treated groups, and one of them only received the surgical procedure without induction of CLP (Sham). The others received intraperitoneal saline 0.9%, antibiotic (Ceftriaxone or ertapenem) and β-lapachone 24 hours before, induction time (Pretreatment) of CLP and 7 days after CLP (Post treatment). The survival rate was analyzed for a period of 16 days. After 12, 24 hours and 7 days of the surgical procedure the samples of the animals of each group were collected and evaluated the leukocyte migration, bacterial load, oxidative parameters (NO, MDA and TEAC) and phagocytosis. In addition, the cell viability of the compound in different concentrations was investigated in vitro. The group pretreated with β lapachone showed an increase in the survival rate of 100% in 16 days. Treatment with β-lapachone caused an increase in the migration of mononuclear cells and reduced the number of neutrophils to the peritoneum. It also showed reduced bacterial load, reduced NO and MDA levels and increased serum antioxidant levels. On the other hand, there was an increase in the concentrations of MDA in samples of animal organs despite the increase of total antioxidants. With regard to posttreatment, there was an increase in survival of 60% and some parameters similar to the CLP group treated with saline. In the cell viability assay it was found that the concentration of 1.00 μM maintained 82% viable. Thus, the best results of the potential pharmacological effect of the compound on pretreatment may have occurred because the therapeutic intervention occurs earlier in the disease process compared to the clinical situation.
Acesso aberto (Open Access)
Avaliação do potencial microbicida das folhas da espécie Ayapana triplinervis Vahl.
(Universidade Federal do Pará, 2013-12-06) LOPES, Tamyris Regina Matos; GONÇALVES, Ana Cristina Baetas; http://lattes.cnpq.br/6886126078022769; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390
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)
Efeito da temperatura e molaridade na avaliação das atividades antimicrobiana, citotóxica e antioxidante do bio-óleo da semente do açaí (Euterpe oleracea, Mart.)
(Universidade Federal do Pará, 2024-08) SILVA, Iago Castro da; MACHADO, Nélio Teixeira; http://lattes.cnpq.br/5698208558551065; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390; https://orcid.org/0000-0002-3328-5650
Açaí, a fruit from the Amazon, is valuable both economically and nutritionally. Its seeds, which are typically discarded, can be converted into bio-oil through pyrolysis (a process of thermochemical degradation of residual biomass), offering a sustainable alternative to fossil fuels. This study explores how temperature and molarity with Potassium Hydroxide (KOH) and Hydrochloric Acid (HCl), which are chemical impregnation reagents in the process, affect the antimicrobial, antioxidant, and cytotoxic activities of the produced bio-oil. Tests were conducted using Gas Chromatography coupled with Mass Spectrometry (GC-MS) and assays to evaluate antimicrobial, antioxidant, and cytotoxic activities at different temperatures (350, 400, and 450 °C) and molarities (0.5 M, 1.0 M, and 2.0 M). Phenolic compounds were the most abundant in the bio-oil (55.70%), followed by cyclic and aromatic hydrocarbons (11.89%) and linear hydrocarbons (9.64%). Despite a reduction in oxygenated compounds, the bio-oil retained bacteriostatic activity against Escherichia coli and Staphylococcus aureus across various temperature ranges, with notable effectiveness at 350 °C. Antioxidant activity was highest at 350 °C and at lower molarities. Furthermore, lower concentrations of acidic impregnation exhibited cytotoxic effects at high temperatures. Thus, bio-oil from açaí seeds generated through pyrolysis shows potential for antioxidant and antimicrobial activities, suggesting feasibility for further testing in dilutions with lower cytotoxicity.
Desconhecido
O efeito in vitro dos compostos ácido alfa-lipoico e resveratrol em parâmetros do estresse oxidativo durante o uso da poliquimioterapia para hanseníase
(Universidade Federal do Pará, 2014-10-20) PESSÔA, Mariely Cristine Amador; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390
The leprosy is an infectious disease that represents a major preoccupation in global public health in 21st century. The treatment with Multi Drug Therapy (MDT) approved by the World Health Organization (WHO) is the best treatment to Mycobacterim leprae infection; however, is one of the factors of increasing Reactive Oxygen Species (ROS) production and the development of methemoglobinemia and hemolytic anemia in these patients. The aim of this study was to verify the oxidative damage in leprosy patients receiving MDT, by evaluation of hematological and oxidative stress biomarkers, and identify the effects of in vitro treatment with antioxidants alpha-lipoic acid (ALA) and resveratrol (RSV) in antioxidant enzymes activity and prevention of methemoglobinemia. The results revealed a decrease in RBC count and reticulocytosis in patients receiving MDT during the 4th and 7th month of treatment. The percentual of methemoglobin increased since the fifth month of treatment with MDT, and the treatment with 100 μM RSV-treated and ALA-treated preserved the values similar to control group only in 4th to 6th month of MDT samples. The leprosy patients presented values of SOD activity similar to the control group and a decreased CAT activity, leading to an inbalance in the ratio of both enzymes and possibly resulting in an over-producing of H2O2. The treatment with RSV and ALA in 100 μM and 500 μM concentrations increases twice the SOD activity in 4th month patient samples; however, these concentrations did not change CAT and SOD activities found in leprosy patients. Such results demonstrate that RSV and ALA did not show antioxidant activity in installed oxidative stress, and subsequent studies are necessary to evaluate dose-dependent and time-dependent concentrations of RSV and ALA to prevent oxidative damage in chronic infectious diseases.
Acesso aberto (Open Access)
Efeito protetor de antioxidantes na formação de metemoglobina induzida pelo metabólito dapsona-hidroxilamina in vitro
(Universidade Federal do Pará, 2017-07-11) VARELA, Everton Luiz Pompeu; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390
Dapsone used in leprosy therapy its metabolite dapsone-hydroxylamine are potent pro-oxidant agents that cause acquired methemoglobinemia. For the treatment of this disease is used as antidote the Methylene Blue, however in high doses this antidote becomes pro-oxidant. In this sense, antioxidant substances may be potential alternatives to methylene blue for the treatment of methemoglobinemia. In this study we investigated the effect of antioxidants Ebselen, N-acetylcysteine, R-lipoic acid and L-lipoic acid on oxidative damage induced by dapsone-hydroxylamine in human erythrocytes, in vitro. Our results demonstrated that pre-treatment with antioxidants Ebselen, N-acetylcysteine, R-lipoic acid and S-lipoic acid prevented the formation of methemoglobin, reduction of glutathione and lipid peroxidation induced by the metabolite dapsone-hydroxylamine in human erythrocytes, In vitro. These substances were able to increase the antioxidant capacity of the erythrocyte associated with increased concentration of glutathione. Thus, antioxidants acted to reduce the oxidation of hemoglobin and / or directly or indirectly impeded the action of the metabolite dapsone-hydroxylamine. Our results indicate that the antioxidants tested can protect erythrocytes against oxidative damage under experimental conditions, suggesting that antioxidants may serve as the most effective and safe antidote in the treatment of methemoglobinemia.
Acesso aberto (Open Access)
Efeito protetor de antioxidantes na metemoglobina e no dano em dna induzidos pela dapsona-hidroxilamina in vitro
(Universidade Federal do Pará, 2016-06-21) GOMES, Antonio Rafael Quadros; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390
Dapsone (DDS) is one of the drugs used in polychemotherapy of leprosy associated with rifampicin and clofazimine. Of these drugs, DDS is primarily responsible for adverse reactions, such as methemoglobinemia and hemolytic anemia. These reactions are related to the DDS metabolite, dapsone hydroxylamine (DDS-NOH). In an attempt to promote the reduction of toxic effects are studied alternative therapies with antioxidants. This work aimed to evaluate the protective effect of N-acetylcysteine (NAC), A. brasiliensis and Glutathione ethyl ester (GSH-EE) in methemoglobin (MetHb) and DNA damage induced by DDS-NOH in vitro , correlating to oxidative stress parameters. For this, suspensions of human erythrocytes to 50% were pre- and post-treated with NAC, A. brasiliensis and GSH-EE in different concentrations, being exposed groups DDS-NOH to induce the formation MetHb. It also assessed whether the activity of enzymes-SOD and CAT and GSH levels, TEAC and MDA. In leukocytes evaluated the induction of ROS intracellularly using DCFH-DA and the damage to DNA by comet assay. The results showed that the DDS-NOH metabolite was capable of inducing MetHb in vitro, this dose-dependent effect. Regarding the pre-treatment, all the antioxidants prevented MetHb formation induced by DDS-NOH, as well as post-treatment. For SOD, only the pre-treatment with NAC and A. brasiliensis reduced SOD activity. In the post-treatment, there was increased when treated with antioxidants. Pre-treatment with NAC and GSH-EE increased CAT activity, moreover A. brasiliensis reduced, as after treatment with antioxidants. As for GSH levels, pre-treatment with NAC and GSH increased A. brasiliensis, on the other hand, did not alter after treatment. Regarding TEAC did not change. With respect to oxidative damage in the pre-treatment A. brasiliensis and GSH-EE reduced MDA. In the post-treatment, there was an increase in group A. brasiliensis and reduced GSH-EE group. Only the NAC was shown to be effective in removing the intracellular ROS induced by DDS-NOH in leukocytes. While in erythrocytes, a NAC and A. brasiliensis were able to reduce this effect. In the study of the comet assay, the DDS-NOH was able to induce DNA damage in peripheral blood leukocytes, however this damage was reduced when treated with NAC and A. brasiliensis. It can be concluded from our data that the evaluated antioxidants have therapeutic potential in the prevention of MetHb and DNA damage induced by DDS-NOH in vitro, more effective NAC against these effects.
Acesso aberto (Open Access)
Efeito protetor do ácido alfa lipóico sobre a lesão hepática, induzida por dapsona em modelo animal
(Universidade Federal do Pará, 2018-07-06) SAKAI, Joni Tetsuo; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390
The liver is the main organ involved in the biotransformation of xenobiotics, with the ability to convert hydrophobic compounds into water soluble, more easily eliminated by the body. Dapsone (DDS) is part of the multidrug therapy (MDT) of leprosy treatment, its metabolite is related to the generation of free radicals in hematological and neural cells, being thus directly involved in the main adverse reactions caused by its use. Due to its conversion cycle, which involves the reaction with iron present in the liver, DDS also accumulates in the liver, remaining longer in this organ, thus favoring tissue damage, such as drug hepatitis. In this context, the objective of the present study was to evaluate the protective effect of Alpha Lipoic Acid (ALA) on the liver damage caused by DDS in mice, after treatment. In this study, treatment with dapsone induced hepatic damage, with increase of Aspartate aminotransferase and alkaline phosphatase, as well as oxidative stress, by increasing lipid peroxidation and decreasing both glutathione levels and total antioxidants. These processes may be associated with accumulation of hepatic iron in the body. Already post-treatment with the antioxidant Alpha Lipoic Acid, this was able to decrease the levels of Aspartate aminotransferase and Alkaline Phosphatase, reverse lipid peroxidation and raise levels of GSH and total antioxidants. In addition, ALA also inhibited the accumulation of hepatic iron induced by dapsone in mice. Our results indicate that the antioxidant tested has a therapeutic potential against hepatic damage caused by dapsone in patients with leprosy.
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 do tratamento subcrônico com fluoxetina sobre os comportamentos e parâmetros oxidativos de ratos submetidos ao exercício físico exaustivo
(Universidade Federal do Pará, 2017-08-25) LEAL, Jerusa de Carvalho; MAIA, Cristiane do Socorro Ferraz; http://lattes.cnpq.br/4835820645258101; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390
Fluoxetine is an antidepressant drug of the selective serotonin reuptake inhibitor class, its use may be a therapeutic alternative in reversing or reducing the changes caused by low serotonergic activity. The increase in serotonergic levels can also be induced by regular physical exercise, in that sense, the health benefits and the prevention of diseases that this type of exercise are promoted are already well reported. However, when exercise is practiced exhaustively it may induce increased oxidative stress and changes in emotional behavior in humans and experimental animals. Therefore, the objective of this study was to evaluate the effects of subchronic treatment with fluoxetine on the behavior and oxidative parameters in rats submitted to exhaustive physical exercise in forced swimming. Therefore, adult male rats of Wistar strain were divided into sedentary animals and exposed to exhaustive exercise subcronically that were treated with fluoxetine 10 mg / kg / day (NaCl 0.9%) and saline either via i.p. for 7 days. After 30 minutes of intoxication the animals were individually exposed to exhaustive physical exercise for 20 minutes. On the eighth day of the experiment, the open field test (TCA) and the high cross labyrinth (LCE) were performed to evaluate spontaneous locomotion and anxiety - like behavior, respectively. The animals were then authanized and blood, liver and brain were collected for determination of GSH, TEAC, NO, and MDA levels. The results obtained, the animals treated with fluoxetine associated to exhaustive physical exercise showed reduction in the locomotion caused by the emotional stress in the ACT and reduction in the behavior similar to the anxiety in the LCE. Regarding the parameters of oxidative stress, fluoxetine associated with the practice of exhaustive physical exercise, in general, induced oxidative stress in the organism, mainly in the blood and liver of these animals, with reduction of the levels of GSH and TEAC and increase of levels of NO and MDA. On the other hand, in the brain, treatment with fluoxetine showed protective effect on oxidative stress, with reduction in NO and MDA levels and increase in antioxidant factors. On the data, it is concluded that fluoxetine associated with exhaustive exercise has dual effect of activity in relation to neurobehavioral and oxidative balance, reducing movement and increasing the anxiolytic effect, demonstrating antioxidant or pro-oxidant depending on the tissue or organ evaluated.
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)
Evaluation of the acute toxicity and antioxidant activity of Justicia secunda methanolic extract in a murine sepsis model
(Universidade Federal do Pará, 2024-09) DAVIS, Kelly; LIMA, Kely Campos Navegantes; http://lattes.cnpq.br/7998567135164137; HTTPS://ORCID.ORG/0000-0001-8613-3223; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390; https://orcid.org/0000-0002-3328-5650
Sepsis is a clinical condition that involves a dysregulated immune response to an infection, leading to complications such as organ dysfunction. The condition begins with hyperinflammation, followed by an increase in oxidative stress and depletion of antioxidant defenses. The rates of sepsis and septic shock have increased markedly in the last couple of decades. Therefore, the search for new therapies to aid in sepsis treatment is important. Justicia secunda Vahl is a widely used specie in traditional medicine. It has anti-inflammatory, antinociceptive, antioxidant, antianemic, antidiabetic, and antimicrobial properties due to secondary metabolites such as flavonoids, polyphenols, alkaloids, and terpenes. We evaluated a J. secunda methanolic extract (JSLS) in an acute oral toxicity test and as a pretreatment in a murine cecal ligation and perforation (CLP) sepsis model. In the acute oral toxicity test, we evaluated clinical parameters for 14 days after a single dose of 2000 mg JSLS/kg body weight, as well as oxidative stress parameter in organ samples. Subsequently, we evaluated the survival and antioxidant parameters of septic mice pretreated with 400 mg JSLS/kg body weight. In the acute oral toxicity test, there were no signs of toxicity, suggesting that JSLS has a median lethal dose greater than 2000 mg/kg body weight. JSLS pretreatment improved the survival rate, clinical parameters, antioxidant levels, and hematological profile of septic mice. We conclude that JSLS could be applied as a coadjutant agent to manage oxidative stress-related diseases. Additional studies are needed to better elucidate the mechanisms, as well as the effective dose of the chemical compounds present in JSLS.