Efeitos do butirato de sódio sobre a disfunção endotélial causada por lisofosfatidilcolina

Abstract

Endothelial dysfunction is a chronic condition, which begins with oxidative stress in response to the lysophosphatidylcholine (LPC) component, present in oxidized LDL (LDLox), which is a key event for the generation of an inflammatory response that may culminate in the development of atherosclerosis and its complications. The fundamental role of endothelial (eNOS) and neuronal (nNOS) nitric oxide synthases in maintaining vascular homeostasis is recognized and that its decoupling is closely linked to the clinical evolution of endothelial dysfunction. In the search for new substances that can act in the prevention or treatment of cardiovascular comorbidities, studies involving dietary components have stood out. Butyrate is produced by the body through bacterial fermentation of fibers in the colon and is the main energy source for colonocytes. Several studies in recent years have shown that butyrate has anti-inflammatory, anti-oxidant, anti-atherogenic effects, among other effects. Since endothelial dysfunction is the key initial event for the development of severe cardiovascular comorbidities, and butyrate has properties that make it an excellent candidate for studying its effect on endothelial dysfunction. The aim of this work was to evaluate the effects of sodium butyrate on endothelial dysfunction caused by PCL. For this purpose, male C57BL6 / J mice, aged 10-12 weeks, were euthanized and their thoracic aorta was divided into rings and mounted in an organ bath to assess vascular reactivity. The results showed that butyrate, at its lowest test concentration, was able to improve endothelial dysfunction caused by LPC and that this effect was due to the action of nNOS present in the endothelium. Flow cytometry and western blot studies were also carried out with endothelial cells (EA.Hy926) pre-treated with LPC and then exposed to butyrate concentrations, and then stimulated with ACh. The treatment with butyrate led to an increase in NO production, and a decrease in hydrogen peroxide (H2O2) and superoxide anion (O2-). The present study showed for the first time that treatment with sodium butyrate was able to reverse the endothelial dysfunction caused by LPC by increasing NO via normalization of nNOS activity, decreasing ROS and by regularizing the ERK1 / 2 activity. The results show that treatment with sodium butyrate prevents the dysfunctional response mediated by LPC.