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

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

Navegar

Agora exibindo 1 - 2 de 2

Acesso aberto (Open Access)
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)
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.

Navegar

Navegando Dissertações em Farmacologia e Bioquímica (Mestrado) - FARMABIO/ICB por Agência de fomento "CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico"