Dissertações em Farmacologia e Bioquímica (Mestrado) - FARMABIO/ICB

URI Permanente para esta coleçãohttps://repositorio.ufpa.br/handle/2011/13299

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Efeito citoprotetor e cicatrizante gástrico do extrato padronizado de Euterpe oleracea Mart.
(Universidade Federal do Pará, 2024-05) SOUZA, Keyla Rodrigues de; MELLO, Vanessa Jóia de; http://lattes.cnpq.br/9437589201689717
A gastric ulcer is an acidic peptic lesion of the digestive tract resulting from an imbalance between the factors that damage the mucosa and those that protect it. It is a prevalent disease throughout the world and the medications used to treat it, although efficient, have side effects. Among these, açaí (Euterpe oleracea Mart.), has high antioxidant and anti-inflammatory capacity due to its composition of bioactive phytochemicals that include the class of anthocyanins, proanthocyanidins, and other flavonoids with promising health effects. The present work investigated the cytoprotective and gastric healing activity of the standardized extract of Euterpe oleracea Mart. (EO). Initially, the ability of EO to promote increased cell migration of epithelial-type cells (Vero) in the in vitro healing model was evaluated. In the spectrum of evaluation of in vivo antiulcer activity, initially, the cytoprotective activity of EO was determined in gastric ulcer models induced by ethanol and indomethacin. Furthermore, the action of EO on gastric secretion was investigated. The in vivo healing effect was evaluated in a gastric ulcer model induced by acetic acid. Treatment with EO at a concentration of (1 μg/mL) promoted a significant increase in cell migration after 48 hours. Pre-treatment with EO at doses of (2.5 μL/g and 10 μL/g) reduced the area of gastric lesions in ulcer models induced by ethanol and indomethacin. EO was not able to increase pH and reduce acidity or volume of gastric secretion to levels similar to animals treated with omeprazole (20 mg/kg) in a pylorus ligation model. In the gastric ulcer model induced by acetic acid, treatment with EO at doses of (2.5 μL/g and 10 μL/g) for eight days reduced the area of the acid-induced gastric ulcer, increasing the healing rate when compared to animals without treatment (one way ANOVA, post-Tukey test p < 0.0001). EO treatment in the acetic acid model also increased catalase activity, increased total glutathione levels, and reduced malondialdehyde and nitrite levels compared to untreated animals. According to the results, the standardized extract of Euterpe oleracea Mart. (EO) showed a healing effect in both in vitro and in vivo studies. It presented a cytoprotective effect that is probably not related to a capacity to modulate gastric secretion, but possibly related to the reduction of oxidative stress and its healing effects.
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Efeitos citotóxicos e mecanismo de ação da eleuterina isolada de Eleutherine plicata em modelo in vitro de células c6
(Universidade Federal do Pará, 2024-05) SHINKAI, Victória Mae Tsuruzaki; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978; https://orcid.org/0000-0003-3647-9124
Glioblastoma multiforme (GBM) is the most prevalent malignant primary tumor of the central nervous system (CNS). GBM cells are characterized by rapid proliferation and aggressive migration. There is growing demand for new therapies to treat this tumor, due to current therapeutic limitations. Quinone derivatives from plants have received increased interest as potential antiglioma drugs due to their diverse pharmacological activities such as inhibition of cell growth, inflammation, tumor invasion and promotion of tumor regression. The herb Eleutherine plicata, popularly known as Marupazinho, is widely used in popular medicine due to its pharmacological properties, containing quinone derivatives, more specifically naphthoquinones. Previous studies have demonstrated the antiglioma activity of Eleutherine plicata, which is related to three main naphthoquinone compounds – eleutherine, isoeleutherine and eleutherol – but mechanism of action remains unclear. Thus, the objective of this study was to investigate the potential cytotoxic and antiproliferative effect of eleutherin in an in vitro model of glioblastoma (C6 lineage). In vitro cytotoxicity was assessed by the MTT assay; Morphological changes were assessed by phase contrast microscopy. Apoptosis was determined by the annexin V-FITCpropidium iodide assay, and antiproliferative effects were assessed by the colony formation assay. Protein kinase B (AKT/pAKT) expression was measured by western blot, and telomerase reverse transcriptase mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The results obtained indicated that eleutherin, isolated from the Hexanic fraction, had a cytotoxic effect on the C6 lineage. Structural changes were observed by image capture, with a significant reduction in colony formation, induction of apoptosis, inhibition of pAKT and reduction in telomerase expression after treatment. Thus, our study showed that the eleuterin molecule has cytotoxic activity in C6 lineage glioma.
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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.
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Existe uma relação entre as frequências dos polimorfismos do gene TSHR e os marcadores de ancestralidade genética em pacientes com hipotireoidismo congênito primário?
(Universidade Federal do Pará, 2024-10) LOURENÇO, Victor Henrique Botelho; ALVES, Erik Artur Cortinhas; http://lattes.cnpq.br/9125390243566397; HTTPS://ORCID.ORG/0000-0001-8824-8075; SILVA, Luiz Carlos Santana da; http://lattes.cnpq.br/6161491684526382; https://orcid.org/0000-0003-1017-6221
Literature shows a correlation between ethnicities and pathogenic variants of the receptor TSH hormone gene (TSHR). Some of these polymorphisms can be as risk factors for the development of Primary Congenital Hypothyroidism (PCH). In this study, we investigate the relationship between the frequencies of TSHR gene polymorphisms with the genetic influence of African, Amerindian, and European ancestry informative markers in patients diagnosed with PCH in an Amazonian population in Brazil. The study was conducted on samples of 106 patients diagnosed with PCH. Genomic DNA was isolated from peripheral blood samples, and 10 exons from the TSHR were automatically sequenced. Ancestry-Informative Marker identification was performed using a panel of 48 markers, and the results were compared with parental Amerindian, Western European, and Sub-Saharan African populations using Structure v2.3.4 software. Four nucleotide alterations were identified among 49 patients. The distribution of tested ancestry markers among the 106 patients indicated a significant difference in the percentages of Amerindian (32.2%), European (41.80%), and African (25.9%) ancestry. A logistic regression analysis revealed no significant association between the rs2075179 and rs1991517 polymorphisms and genetic ancestry. This study found no evidence of a relationship between polymorphic TSHR gene variants and genetic ancestry markers in patients with PCH.
Acesso aberto (Open Access)
Potencial neuroprotetor da atividade física em populações ribeirinhas da Amazônia expostas ao mercúrio
(Universidade Federal do Pará, 2025-05) NAZARÉ, Caio Gustavo Leal de; OLIVEIRA, Marcus Augusto de; http://lattes.cnpq.br/6036530007649294; HTTPS://ORCID.ORG/0000-0002-4772-9929; LOPEZ, Maria Elena Crespo; http://lattes.cnpq.br/9900144256348265; https://orcid.org/0000-0002-1335-6853
Mercury is a highly toxic metal and is among the three substances with the greatest potential threat to human health. Its organic form, methylmercury, is particularly dangerous to human health due to its ability to easily cross biological barriers. The brain is a critical target for methylmercury, where it can cause neurological disorders, including motor, visual, auditory, behavioral, and cognitive deficits. Glial cells are closely involved in the mechanisms mediating such disorders and can either protect or damage the central nervous system (CNS), depending on the context. Moreover, no pharmacological treatment has proven effective against mercury intoxication to date, and literature has shown that both physical exercise and physical activity are capable of modulating glial aspects involved in the pathophysiology common to various neurological conditions and methylmercury intoxication. Thus, a potentially therapeutic and non-pharmacological approach, such as physical exercise – and even physical activity – would be particularly suitable for vulnerable populations who are economically, socially, and geographically disadvantaged, such as the riverine communities of the Amazon, who are chronically exposed to methylmercury through the consumption of contaminated fish. This study aims to assess whether physical activity profiles can influence the symptomatology of methylmercury intoxication in riverside residents of the Tucuruí Lake region. Interviews were conducted to obtain a profile of physical activity and self-reported neurological symptoms, and total mercury was measured from hair samples. Our results point to a possible and complex relationship between hair mercury levels and physical activity, suggesting that physical exercise may be a viable alternative to be included in daily life.
Acesso aberto (Open Access)
A sinalização adenosinérgica na regulação da gravidade da sepse e da liberação de armadilhas extracelulares de neutrófilos (NETs)
(Universidade Federal do Pará, 2024-09) PAMPOLHA, Ana Flavia Oliveira; CUNHA, Fernando de Queiroz; http://lattes.cnpq.br/2869737621338203; HTTPS://ORCID.ORG/0000-0003-4755-1670; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390; https://orcid.org/0000-0002-3328-5650
Neutrophils express different purinergic receptors, including four adenosine-ligand P1 receptors, which regulate their primary functions, such as migration and production of inflammatory mediators, including neutrophil extracellular traps (NETs). In sepsis, NETs exhibit a dual role: microbicidal properties but also contribute to organ damage, leading to multiple organ failure and worsening the clinical condition. In this study, we investigated the role of adenosine in NETs release and the progression of experimental sepsis induced by the Cecum Ligation and Puncture (CLP) or endotoxemia models. We observed that treatment of mice subjected to both models with adenosine deaminase (ADA), which metabolizes adenosine to inosine, aggravates organ damage and reduces the survival rate of septic animals. Supporting these findings, we demonstrated that NET production in vitro by neutrophils stimulated with PMA was enhanced by ADA treatment and reduced by NECA, a molecule that mimics adenosine's actions. The modulation of NET production by adenosine was attributed to the activation of A2AAR receptors. In conclusion, our results suggest that during sepsis, adenosine is released and decrease NET production via A2AAR activation.

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