Ações terapêuticas de Echinodorus grandiflorus frente ao modelo de aterosclerose

Abstract

Excess weight and dyslipidemia are among the most serious health problems in Western societies. These conditions increase the risk of heart disease and have been associated with a higher prevalence of cardiac arrhythmias and sudden death. The present study investigated the cardioprotective effects of Echinodorus grandiflorus on dyslipidemia, atherosclerosis and ventricular remodeling of New Zealand male rabbits fed a 1% high cholesterol diet (CRD). First, we obtained an ethanol soluble fraction from the infusion of E. grandiflorus (ESEG) leaves and performed a detailed phytochemical study by high performance liquid chromatography and mass spectrometry. Then, for 60 days, the animals were fed the CRD or a cholesterol-free diet (white, item 1 or negative control, article 2). After 30 days of the initiation of CRD, rabbit groups were treated orally (v.o.) with vehicle (filtered water) (negative control, item 1 or positive control, article 2) o ESEG (10, 30 e 100 mg/kg) ou sinvastatina (2,5 mg/kg). Blood collection was performed on the first day of the experiment, 30 and 60 days later. At the end of 60 days, the electrocardiographic profile, serum lipid levels, oxidized low density lipoprotein (oxLDL) concentration, levels of malondialdehyde (MDA), and serum levels of nitrotyrosine, interleukin -1 (IL-1β), IL-6, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1) were investigated. Samples of the right ventricle, aortic arch and thoracic segment were also collected to investigate the tissue antioxidant defense system and histopathological and morphometric analyzes. Statistical analyzes were performed by means of unidirectional analysis of variance (ANOVA) followed by the Dunnett test or the Kruskal-Wallis test followed by the Dunn test. Values of p <0.05 were considered statistically significant. ESEG treated animals had similar body weight gain to rabbits that were treated with the standard commercial diet, unlike animals that were fed the CRD and treated with vehicle alone after 60 days. Phytochemical investigation of ESEG showed a large amount of flavonoid C- and O-glycoside. Electrocardiographic analysis showed important morphological and functional alterations in the animals fed with CRD, indicating hypertrophy of the left ventricle, myocardial flaccidity, fatty degeneration, and concentric left ventricular hypertrophy. An expressive increase in the levels of total cholesterol and fractions, oxLDL, triglycerides, nitrotyrosine and TBARS, besides a significant decrease in the activity of the tissue antioxidant defense system of the ventricular muscle and in the different arterial branches were also detected. All of these changes were accompanied by significant increases in IL-1β, IL-6, sICAM-1 and sVCAM-1 levels, and by the development of atherosclerotic lesions in the intima-layer of the whole arterial system evaluated. Oral administration of ESEG 100 mg/kg significantly reduced serum lipid levels in rabbits fed CRD. This treatment also modulated the arterial and cardiac antioxidant defense system, reducing the oxidation of lipids and proteins. Similarly, serum levels of IL-1β, IL-6, sICAM-1 and sVCAM-1 decreased significantly, accompanied by a reduction of cardiac and atherosclerotic lesions in all arterial branches. The data presented here showed that ESEG 100 mg/kg can be considered promising for the prevention of cardiac and vascular changes induced by a high cholesterol diet.