Influência dos capsinóides sobre a reatividade e estresse oxidativo vascular de ratos com obesidade

• Ano de defesa: 2024
• Autor(a) principal: Cordeiro, Evellyn Rodrigues
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal do Espírito Santo; BR; Doutorado em Ciências Fisiológicas; Centro de Ciências da Saúde; UFES; Programa de Pós-Graduação em Ciências Fisiológicas
• Palavras-chave em Português: Obesidade; Remodelamento vascular; Estresse oxidativo; Aorta; Capsinóides; Ratos; Obesity; Vascular remodeling; Oxidative stress; Capsinoids; Rats; Fisiologia
• Link de acesso: http://repositorio.ufes.br/handle/10/18326

Obesity is one of the biggest public health problems and its pathophysiology involves metabolic, structural and functional changes in different tissues due to several mechanisms. Such changes can modify vascular homeostasis and are associated with the development of cardiovascular diseases such as arterial hypertension, coronary disease and atherosclerosis, as well as type 2 diabetes mellitus, which increase the risk of mortality. The deleterious effects observed in obesity include the process of dysfunctional vascular remodeling with consequent rigidity after structural and functional modifications in the intima, media and adventitial layers of blood vessels. In addition, oxidative stress, an important pathological mechanism involved in obesity, contributes to the development of pro-oxidant and pro-inflammatory states in the vasculature, which promote dysfunctional remodeling and vascular stiffness, increasing the risk of pathological outcomes observed in cardiovascular events. Studies have shown that capsinoids, bioactive peptides present in pepper, are potent antioxidants and antiobesogenics, playing a role in modulating oxidative stress induced by obesity. However, no research was found that analyzed their effects on oxidative stress and vascular remodeling caused by obesity. Therefore, the aim of the present study was to investigate the effects of chronic administration of capsinoids on vascular reactivity, morphology and oxidative stress in the aorta of obese rats induced by a saturated high-fat diet. Wistar rats (n=18, 30 days) were randomized into 2 groups: standard diet (fed with standard diet; DP = 8) and high-fat diet (fed with saturated diet rich in fat; DH = 10). Control = C (fed with standard diet) and obese = Ob (fed with saturated high-fat diet). The experimental protocol lasted 27 consecutive weeks, consisting of two moments: 1) Induction (4 weeks) and maintenance of obesity (19 weeks) and; 2) Chronic exposure to treatment with capsinoids (8 weeks). After 19 weeks, DP and DH animals were redistributed and randomly renamed into four distinct groups according to the absence and/or presence of capsinoids (Cap) and obesity (Ob): Control (C); Obese (Ob); Control with capsinoids (Ccap); Obese with capsinoids (ObCap). Chronic administration of capsinoids (10 mg/kg) was performed daily by orogastric gavage. Body composition was assessed by monitoring mass, fat and body adiposity index. Vascular morphology was determined by analyzing remodeling and vascular collagen deposition. Vascular reactivity was analyzed in the aorta by pharmacological assays involving the analysis of eNOS bioavailability, production of reactive oxygen species, participation of NADPH oxidase, AT1 receptors and the COX pathway. The results show that obesity increased body mass and adiposity index, however, chronic administration of capsinoids was not able to restore these parameters. Considering the glycemic and lipid profiles, obesity altered glycemia and total cholesterol, however treatment with capsinoids was also not able to restore these changes. The results also indicate that no changes were observed in plasma biomarkers of oxidative stress. In the vascular context, obesity increased reactivity through an increase in reactive oxygen species, especially superoxide anion, activation of AT1 receptors and release of contractile prostanoids via COX. Treatment with capsinoids reduced obesity-induced vascular reactivity through the participation of eNOS, in addition to reducing superoxide anion and COX-derived prostanoids. It was also able to increase the medial layer of vascular smooth muscle and reduce collagen deposition, preventing obesity-induced pathological remodeling. In conclusion, chronic administration of capsinoids at a dose of 10 mg/kg restores vascular reactivity parameters in obesity through vasodilation via eNOS and reduction of oxidative stress. Furthermore, it also shows that the treatment was able to prevent the pathological vascular remodeling process caused by obesity