Nutrition and Genomics Laboratory, Basic and Experimental Nutrition Department, Institute of Nutrition, Rio de Janeiro State University, Rio de Janeiro, Brazil.
Université de Lyon, INSERM U1060, CarMeN, INSA de Lyon, Univ Lyon-1, F-69621, Villeurbanne, France.
Exp Physiol. 2020 Mar;105(3):542-551. doi: 10.1113/EP088080. Epub 2020 Jan 30.
What is the central question of this study? Does a polyphenol-rich extract from açaí have a potential role in preventing uraemic toxin-induced endothelial cell dysfunction? What is the main finding and its importance? Polyphenols from açaí prevented cell death, restored migratory capacity, protected from inflammation and contributed to the restoration of the antioxidant response in endothelial cells exposed to uraemic toxins. The protective role of açaí against toxic effects exerted by uraemic toxins presents a potential new therapeutic target in endothelial cells.
In chronic kidney disease (CKD), progressive loss of kidney function results in the accumulation of protein-bound uraemic toxins such as p-cresyl sulfate (pCS) and indoxyl sulfate (IS). Among strategies to ameliorate the harmful actions of uraemic toxins, phenolic compounds have been extensively studied. The main goal of this work was to evaluate the antioxidant and anti-inflammatory actions of phenolic-rich açaí seed extract (ASE) in response to endothelial dysfunction induced by IS and pCS, in human umbilical vein endothelial cells (HUVECs). Cells were treated with ASE (10 µg ml ) in the presence or absence of IS (61 µg ml ) and pCS (40 µg ml ). Cell viability, cell death, cell migratory capacity and inflammatory biomarker expression were evaluated. Cellular antioxidant response was measured through the activity and expression of antioxidant enzymes, and oxidative damage was evaluated. IS and pCS lowered cell viability, triggered cell death and lowered the migratory capacity in endothelial cells (P < 0.05). ASE prevented cell death and restored the migratory capacity in cells exposed to IS. Both toxins up-regulated pro-inflammatory cytokine expression, and ASE was able to beneficially counteract this effect. Tumour necrosis factor-α secretion was greater in uraemic toxin-treated cells and ASE reversed this phenomenon in cells treated with both toxins concomitantly (P < 0.05). With regard to the antioxidant response, superoxide dismutase expression was strikingly lower in cells treated with both toxins, and ASE inhibited this harmful effect (P < 0.05). From the results, we conclude that ASE exerted protective effects on inflammation and oxidative stress caused by uraemic toxins (particularly by IS) in human endothelial cells.
本研究的核心问题是什么？富含原花青素的巴西莓提取物在预防尿毒症毒素诱导的内皮细胞功能障碍方面是否具有潜在作用？主要发现及其重要性是什么？巴西莓中的多酚可防止细胞死亡、恢复迁移能力、防止炎症，并有助于恢复暴露于尿毒症毒素的内皮细胞的抗氧化反应。巴西莓对尿毒症毒素产生的毒性作用的保护作用为内皮细胞提供了一个新的潜在治疗靶点。
在慢性肾脏病（CKD）中，肾功能逐渐丧失会导致蛋白结合尿毒症毒素（如对甲酚硫酸盐（pCS）和吲哚硫酸酯（IS））的积累。在改善尿毒症毒素的有害作用的策略中，酚类化合物已被广泛研究。本工作的主要目的是评估富含多酚的巴西莓种籽提取物（ASE）在人脐静脉内皮细胞（HUVEC）中对 IS 和 pCS 诱导的内皮功能障碍的抗氧化和抗炎作用。细胞用 ASE（10μg/ml）处理，同时存在或不存在 IS（61μg/ml）和 pCS（40μg/ml）。评估细胞活力、细胞死亡、细胞迁移能力和炎症生物标志物表达。通过抗氧化酶的活性和表达来测量细胞抗氧化反应，并评估氧化损伤。IS 和 pCS 降低了内皮细胞的活力，引发细胞死亡并降低了迁移能力（P<0.05）。ASE 可防止细胞死亡并恢复暴露于 IS 的细胞的迁移能力。两种毒素均上调促炎细胞因子的表达，而 ASE 可有益地拮抗这种作用。尿毒症毒素处理的细胞中肿瘤坏死因子-α的分泌更高，而 ASE 逆转了同时用两种毒素处理的细胞中的这种现象（P<0.05）。关于抗氧化反应，两种毒素处理的细胞中超氧化物歧化酶的表达明显降低，而 ASE 抑制了这种有害作用（P<0.05）。从结果中我们得出结论，ASE 对尿毒症毒素（尤其是 IS）引起的人类内皮细胞的炎症和氧化应激具有保护作用。
