Ação do ácido clorogênico sobre a sinalização purinérgica e parâmetros oxidativo-inflamatórios em um modelo murino de diabetes mellitus tipo 1

• Ano de defesa: 2026
• Autor(a) principal: Schirmann, Adriel Antonio
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Santa Maria; Brasil; UFSM; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica; Centro de Ciências Naturais e Exatas
• Palavras-chave em Português: Diabetes mellitus; Inflamação; Ácido clorogênico; Sistema purinérgico; Chlorogenic acid; Inflammation; Purinergic system; CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
• Link de acesso: http://repositorio.ufsm.br/handle/1/39025

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the destruction of pancreatic β-cells, resulting in insulin deficiency, persistent hyperglycemia, and the development of oxidative and inflammatory alterations that contribute to disease progression and its complications. Evidence indicates that the purinergic system plays a key role in modulating these processes, making it a potential therapeutic target. In this context, naturally occurring phenolic compounds, such as chlorogenic acid (CGA), have attracted considerable interest due to their antioxidant, anti-inflammatory, and hypoglycemic properties. Therefore, the present study aimed to investigate the effects of CGA on oxidative-inflammatory parameters and components of the purinergic system in a streptozotocin (STZ)-induced murine model of T1DM. Male Swiss mice were rendered diabetic by a single intraperitoneal injection of STZ (200 mg/kg) and treated with CGA (100 mg/kg, p.o.) either 1 h after diabetes induction (acute protocol) or once daily for 7 days (subchronic protocol). Metabolic parameters, survival, oxidative stress markers, nucleotide and nucleoside hydrolysis, gene expression of inflammatory and purinergic mediators, protein expression of purinergic receptors, and in silico analyses investigating the interaction of CGA with enzymes and receptors of the purinergic pathway were evaluated. The results demonstrated that CGA exhibited high molecular affinity for purinergic targets, reduced pancreatic lipid peroxidation, modulated ATP hydrolysis and adenosine degradation, decreased the expression of pro-inflammatory genes associated with the NLRP3 inflammasome, and increased IL-10 expression. In addition, CGA reduced P2X7 receptor protein expression and increased A2A receptor expression, suggesting modulation of purinergic signaling toward a less inflammatory profile. Collectively, these findings indicate that CGA exerts antioxidant, anti-inflammatory, and purinergic modulatory effects, contributing to the attenuation of alterations associated with T1DM. Overall, this study expands current knowledge regarding the mechanisms underlying the interplay among diabetes, inflammation, and purinergic signaling, providing a basis for future investigations into the therapeutic potential of chlorogenic acid and other phenolic compounds in the context of type 1 diabetes mellitus.