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化学过滤器在 UV/ROS 应激下人角质形成细胞和成纤维细胞中的矛盾作用。

Contradictory effects of chemical filters in UV/ROS-stressed human keratinocyte and fibroblast cells.

机构信息

Division of Medical Biochemistry, Biocenter, Medical University of Innsbruck, Austria.

Institute of Pharmacy/Pharmacognosy, University of Innsbruck, Austria.

出版信息

ALTEX. 2019;36(2):231-244. doi: 10.14573/altex.1808201. Epub 2018 Nov 27.

DOI:10.14573/altex.1808201
PMID:30488083
Abstract

Chemical UV-filters are frequently applied as active ingredients in sunscreen to protect from detrimental effects of UV radiation. Regardless, many of these compounds are not well characterized concerning their capacity to counteract UV induced reactive oxygen species (ROS). Intracellular ROS release is an early event upon UV exposure and a crucial trigger of reaction cascades that may provoke adverse effects both in short- and long-term. We report a strategy to assess the capacity of UV-filters (ecamsule, oxybenzone and menthyl anthranilate) to counteract UVA/UVB stress in the human keratinocyte HaCaT and the wildtype Fibs E6/E7 fibroblast cell lines. The reduction of ROS levels was taken as primary endpoint. The effect of treatment on the cells' metabolic activity was analyzed as an indicator of viability post-treatment, to investigate potential immediate and late (photo)toxicity. Additionally, the compounds' antioxidative capacity was investigated using an azo-based radical generator. Established antioxidants, quercetin and N-acetylcysteine, were used as controls. Data showed remarkable differences in the mode of action of the chemical UV-filters, ranging from protective to pro-oxidative properties, indicating the need for more detailed mode of action-based investigations. Certainly, additional consideration and evaluation will be necessary to further extrapolate these in vitro data for the assessment of in vivo exposure situations. However, the presented approach enables parallel investigations of photoprotective and phototoxic effects of UV-filters, and thus can complement and extent existing in vitro testing strategies.

摘要

化学紫外线滤光剂通常被用作防晒霜中的活性成分,以保护免受紫外线辐射的有害影响。然而,许多这些化合物在其对抗紫外线诱导的活性氧(ROS)的能力方面并没有得到很好的描述。细胞内 ROS 的释放是紫外线暴露后的早期事件,也是引发反应级联的关键触发因素,这些级联反应可能会在短期和长期内引起不良反应。我们报告了一种评估紫外线滤光剂(二苯酮-3、氧苯酮和薄荷烷醇氨茴酸酯)在人角质形成细胞 HaCaT 和野生型 Fibs E6/E7 成纤维细胞系中对抗 UVA/UVB 应激的能力的策略。ROS 水平的降低被作为主要终点。将处理对细胞代谢活性的影响作为处理后细胞活力的指标进行分析,以研究潜在的即时和迟发性(光)毒性。此外,还使用基于偶氮的自由基生成剂研究了化合物的抗氧化能力。作为对照,使用了已建立的抗氧化剂槲皮素和 N-乙酰半胱氨酸。数据显示,化学紫外线滤光剂的作用模式存在显著差异,从保护作用到促氧化作用,这表明需要进行更详细的作用模式研究。当然,需要进一步考虑和评估这些体外数据,以进一步推断出这些数据在体内暴露情况评估中的应用。然而,所提出的方法能够平行研究紫外线滤光剂的光保护和光毒性作用,从而可以补充和扩展现有的体外测试策略。

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