Compostos fenólicos do açaí: uma estratégia para minimizar a inflamação e o estresse oxidativo associados às toxinas urêmicas

Abstract

Açaí seed extract (ASE) has shown a protective effect on endothelial dysfunction and renal alterations in a murine model of renovascular hypertension. The main goal of this work was to evaluate the antioxidant and anti-inflammatory potentials of açaí extract in the presence of uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (pCS) in human endothelial cells and in a murine model of chronic kidney disease (CKD). Human umbilical vein endothelial cells (HUVEC) had received different treatments with ASE (10 μg/mL), IS (61 μg/mL) and pCS (40 μg/mL). We evaluated the parameters of cell viability, cell death, migration capacity, inflammatory cytokine production and expression and biomarkers of oxidative stress, as well as cellular antioxidant response. In addition, in an in vivo model of CKD fed with adenine (0.25%), we evaluated biomarkers of renal function and oxidative damage, collagen content in renal tissue, as well as phenolic metabolites profile in plasma and urine of animals, whether treated or not with ASE. IS and pCS reduced endothelial cell viability and prevented cell death, and also decreased endothelial cell cellular migration capacity (p <0.05). ASE was able to prevent cell death and reduction of migratory capacity in IS-treated cells. Both toxins promoted increased expression of proinflammatory cytokines, and ASE prevented this effect. The toxins also promoted increased secretion of TNF-α, and ASE reversed this phenomenon in cells treated with both toxins in concomitance (p <0.05). Antioxidant enzyme expression of superoxide dismutase was decreased in cells treated with both toxins, and ASE was able to prevent this effect (p <0.05). In experimental animals, renal function parameters indicated the onset of CKD, and ASE attenuated the increased plasma urea concentrations and proteinuria (p <0.05). Oxidative damage biomarkers evaluated in renal tissue suggested the presence of oxidative stress in CKD animals. ASE was able to ameliorate this hazard effect. In addition, ASE prevented collagen deposition in renal tissue observed in CKD animals (p <0.05). Hippuric acid was the main metabolite found in urine of Control + ASE and CKD + ASE groups, followed by 3,4-dihydroxyphenylacetic acid and catechin. The urinary excretion of these compounds differed between Control and CKD groups. In plasma from CKD animals, hippuric acid was found to be twice as concentrated in comparison to Control group. Results pointed out to the beneficial effects of ASE on uremic toxin deleterious effects, particularly on IS, in endothelial cells. In vivo, we observed that ASE ameliorated oxidative damage and renal function in chronic kidney disease. The present work shows the protective effect of açaí seed extract, rich in phenolic compounds, on uremic toxins deleterious effects in different experimental models of uremic toxicity