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采用体外人呼吸道上皮组织模型评估二羟丙酮的呼吸毒性。

Assessing the respiratory toxicity of dihydroxyacetone using an in vitro human airway epithelial tissue model.

机构信息

Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States of America.

Division of Biochemistry Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States of America.

出版信息

Toxicol In Vitro. 2019 Sep;59:78-86. doi: 10.1016/j.tiv.2019.04.007. Epub 2019 Apr 5.

Abstract

Dihydroxyacetone (DHA) is an approved color additive used in sunless tanning lotions. Recently, there has been an increased use of DHA in sunless tanning booths in a manner that could result in its inhalation during application. In the present study, we have evaluated the potential for DHA causing toxicity via inhalation using a human air-liquid-interface (ALI) in vitro airway epithelial tissue model. ALI airway models have a close structural and functional resemblance to the in vivo airway epithelium, and thus data generated in these models may have relevance for predicting human responses. To simulate in vivo exposure conditions, we employed a method for liquid aerosol generation that mimics the physical form of inhaled chemicals and used doses of DHA and an exposure frequency reflecting human respiratory exposures during tanning sessions. Compared to the vehicle control, cilia beating frequency (CBF) and MUC5AC secretion were significantly decreased after each exposure. However, time-course studies indicated that both CBF and MUC5AC secretion returned to normal levels within 3 days after the treatment. Matrix metalloproteinase (MMP) release, on the other hand, was decreased 24 h after the first exposure and its level returned to baseline after 5 exposures. No significant morphological changes occurred in the DHA-treated cultures after 5 weekly exposures. Our findings indicate that DHA, at concentrations likely to be experienced by humans, has transient toxic effects on human airway ALI cultures.

摘要

二羟丙酮(DHA)是一种经过批准的用于非日晒晒黑乳液的着色添加剂。最近,在非日晒晒黑 booths 中越来越多地使用 DHA,其在应用过程中可能会被吸入。在本研究中,我们使用人类气液界面(ALI)体外气道上皮组织模型评估了 DHA 通过吸入引起毒性的可能性。ALI 气道模型在结构和功能上与体内气道上皮非常相似,因此这些模型中产生的数据可能与预测人类反应有关。为了模拟体内暴露条件,我们采用了一种模拟吸入化学物质物理形式的液体气溶胶生成方法,并使用了反映人类在晒黑过程中呼吸暴露的 DHA 剂量和暴露频率。与载体对照相比,每次暴露后纤毛摆动频率(CBF)和 MUC5AC 分泌均显著降低。然而,时程研究表明,在治疗后 3 天内,CBF 和 MUC5AC 分泌均恢复正常水平。另一方面,基质金属蛋白酶(MMP)释放在第一次暴露后 24 小时下降,在 5 次暴露后恢复到基线水平。在 5 次每周暴露后,DHA 处理的培养物中未发生明显的形态变化。我们的研究结果表明,在人类可能经历的浓度下,DHA 对人体气道 ALI 培养物具有短暂的毒性作用。

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