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

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

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Apocinina reverte fibrose e disfunção elétrica cardíaca induzida pelo aumento sistêmico de MMP-2 em camundongos adultos
(Universidade Federal do Pará, 2024-09) PONTES, Maria Helena Barbosa Pontes; RODRIGUES, Keuri Eleutério; http://lattes.cnpq.br/0030683756521893; PRADO, Alejandro Ferraz do; http://lattes.cnpq.br/7016475842644161; https://orcid.org/0000-0001-7495-9837
Heart failure (HF) is characterized by the heart's inability to maintain adequate tissue blood flow, associated with deficits in contraction and relaxation, due to either an acute or chronic injurious event. Matrix metalloproteinase 2 (MMP-2) is linked to the pathogenesis and pathophysiology of HF, promoting proteolysis of contractile proteins and oxidative stress. Rescue therapies that directly or indirectly modulate MMP-2 activity could help improve cardiac remodeling and dysfunction. Apocynin inhibits NADPH oxidase, thereby attenuating oxidative stress. This study hypothesizes that apocynin can reverse cardiac remodeling and electrical dysfunction induced by MMP-2 by preventing oxidative imbalance. The aim of this study is to evaluate the effect of apocynin on oxidative imbalance and cardiac remodeling induced by systemic MMP-2 increase in adult mice. Adult male C57BL/6 mice were subjected to two experimental protocols. First, the animals underwent a time course protocol and were divided into two groups: the vehicle group received 0.9% saline via intraperitoneal (ip) injection, and the MMP-2 group received MMP-2 (150 ng/g body weight) via ip injection, for up to 4 weeks. Subsequently, a treatment protocol with apocynin was performed, starting 4 weeks after the cessation of MMP-2 administration. During this period, the animals were divided into four experimental groups: 1) vehicle (received water via gavage); 2) apocynin (50 mg/kg via gavage); 3) MMP-2 (received water via gavage); and 4) MMP-2 + apocynin (50 mg/kg via gavage). At the end of the protocols, all animals underwent electrocardiography, and then their hearts were collected for morphological and biochemical evaluation. During the time course, the MMP-2 group showed increased gelatinolytic activity, oxidative imbalance, fibrosis, decreased heart rate, along with increased RR, PQ, QT, and QTc intervals from the first week of administration, effects that persisted over the four weeks, even without MMP-2 administration. Treatment with apocynin reversed the increase in MMP-2 activity and expression in the heart, as well as oxidative imbalance, lipid peroxidation, hypertrophy, cardiac fibrosis, and electrical dysfunction. We conclude that systemic MMP-2 increase can promote cardiac remodeling through increased MMP-2 activity and expression in cardiac tissue, leading to redox imbalance and electrical dysfunction, and that apocynin treatment was able to reverse the effects induced by MMP-2, suggesting that these effects are dependent on oxidative imbalance and NADPH oxidase.
Acesso aberto (Open Access)
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.
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.
Acesso aberto (Open Access)
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.
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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