Efeitos cardiometabólicos do inibidor SGLT2, Empagliflozina, em modelo experimental de camundongos C57Bl/6 induzido por dieta hiperlipídica

• Autor(a) principal: Cotrin, Juliana Cordovil
• Data de Publicação: 2020
• Outros Autores: [e-mail]
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/18701
• topic: Empagliflozin; Renin angiotensin pathway; Endoplasmic reticulum; Empagliflozina; Sistema renina angiotensina; Estresse do retículo; Dieta hiperlipídica; High-fat diet; CIENCIAS BIOLOGICAS::MORFOLOGIA

The cardiometabolic benefits of empagliflozin are multidimensional and the mechanisms have not been elucidated. Thus, the aim of the present study is to evaluate the effect of treatment with empagliflozin on biometric parameters and gene expression in the local cardiac Renin Angiotensin System (RAS), oxidative stress and endoplasmic reticulum (ERS) pathways. Forty male C57BL/6 mice were fed with a control or high fat (HF) diets for 10 weeks. After this period, the groups were subdivided (C, CE, HF, HFE) and empagliflozin (10mg/kg/day) was administered for 5 weeks. We performed biochemical analyzes, blood pressure (BP) monitoring, oral glucose tolerance test, left ventricle (LV) stereology, cardiomyocytes area (A[car]) morphometry and RT-qPCR for genes related to oxidative stress and ERS in LV, as related to classical and counter-regulatory local LV RAS. Comparing HF and HFE groups, the treatment with empagliflozin reduced body mass (-7%), glucose intolerance (-5%) and insulin resistance (-62%), total plasma cholesterol (-19%), plasma uric acid (-17%) and BP (-15%). Also reduced LV thickness (-15%) and A[car] (-27%), besides decreasing oxidative stress and ERS related genes in LV. The local LV RAS had less activity of the classical pathway and positive effects on counter-regulatory pathway. Our analysis suggests that empagliflozin exerts beneficial cardiometabolic effects beneficial through mechanisms that may be related to the regulation of the RAS pathway corroborating for the reduction of risk factors for cardiovascular diseases.