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槲皮素对银纳米颗粒暴露下肠道屏障及细胞活力的保护作用:来自肠道共培养模型的见解

Protective effects of quercetin on intestinal barrier and cellular viability against silver nanoparticle exposure: insights from an intestinal co-culture model.

作者信息

Sousa Adelaide, Kämpfer Angela A M, Schins Roel P F, Carvalho Félix, Fernandes Eduarda, Freitas Marisa

机构信息

LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.

IUF - Leibniz-Research Institute for Environmental Medicine, Düsseldorf, Germany.

出版信息

Nanotoxicology. 2025 Mar;19(2):141-155. doi: 10.1080/17435390.2025.2450372. Epub 2025 Feb 3.

Abstract

The intestinal epithelium plays a pivotal role as a vital barrier between the external environment and the human body, regulating nutrient absorption and preventing the entry of harmful substances. The human oral exposure to silver nanoparticles (AgNP) raises concerns about their potential toxicity, especially at the intestinal level. The objective of this work was to investigate the potential pro-inflammatory effects of polyvinylpyrrolidone (PVP)-AgNP of two different sizes, 5 and 50 nm, at the intestinal level, while also assessing the protective ability of quercetin against these effects. To address this, an intestinal co-culture model comprising C2BBe1 cells and THP-1 derived macrophages was established, and the effects of 5 or 50 nm PVP-AgNP were studied, alone or in combination with quercetin, over two-time points, 4 and 24 hours. PVP-AgNP, of both sizes, disrupted the barrier integrity within 4 hours of exposure. However, a notable intensification in pro-inflammatory effects was evident only after 24 hours of exposure, especially with smaller PVP-AgNP (5 nm). This resulted in heightened cellular death, increased levels of reactive species, activation of nuclear factor kappa B (NF-кB), and production of interleukin (IL)-8. Quercetin demonstrates the ability to maintain barrier integrity and mitigate oxidative stress, thereby offering protection against the detrimental effects induced by AgNP at the intestinal level.

摘要

肠道上皮作为外部环境与人体之间的重要屏障,在调节营养吸收和防止有害物质进入方面发挥着关键作用。人体经口接触银纳米颗粒(AgNP)引发了对其潜在毒性的担忧,尤其是在肠道层面。本研究的目的是探究两种不同尺寸(5纳米和50纳米)的聚乙烯吡咯烷酮(PVP)-AgNP在肠道层面的潜在促炎作用,同时评估槲皮素对这些作用的保护能力。为此,建立了一种包含C2BBe1细胞和THP-1衍生巨噬细胞的肠道共培养模型,并研究了5纳米或50纳米PVP-AgNP单独或与槲皮素联合使用在4小时和24小时这两个时间点的作用。两种尺寸的PVP-AgNP在暴露4小时内均破坏了屏障完整性。然而,仅在暴露24小时后促炎作用才明显增强,尤其是较小尺寸的PVP-AgNP(5纳米)。这导致细胞死亡增加、活性物质水平升高、核因子κB(NF-κB)激活以及白细胞介素(IL)-8产生。槲皮素具有维持屏障完整性和减轻氧化应激的能力,从而为肠道层面的AgNP诱导的有害作用提供保护。

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