Department of In Vitro Toxicology, Charles River Laboratories, Tranent, Edinburgh, EH33 2NE, UK.
School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, BN2 1GJ, UK.
Regul Toxicol Pharmacol. 2021 Oct;125:105022. doi: 10.1016/j.yrtph.2021.105022. Epub 2021 Jul 30.
The aim of the study was to use multiple in vitro assays to assess the effects of a model irritant, sodium dodecyl sulphate (SDS) (≤10 mM (0.29 %, w/v)), on an in vitro model of the airway, MucilAir™. The use of MucilAir™ in recovery studies was also explored. A 24 h exposure increased IL-8 release at an SDS concentration ≥0.63 mM (0.018 %, w/v). Mucin secretion increased and transepithelial electrical resistance (TEER) decreased at SDS concentrations ≥1.25 mM (0.04 %, w/v). Cytotoxicity (lactate dehydrogenase (LDH) release into basolateral chamber) was observed at SDS concentrations of ≥2.5 mM (0.07 %, w/v). The sensitivity of the assays was IL-8 release > TEER = mucin secretion > LDH release. After 7 days, full or partial recovery was observed for intermediate concentrations of SDS using all assays but not at 5 and 10 mM SDS. Morphologically, erosion and cell loss were observed at these concentrations. Resazurin metabolism at 7 days tended to decrease in a dose-dependent manner at SDS concentrations above 2.5 mM (0.07 %, w/v). Together, these data support a No Observable Effect Level of 0.31 mM (0.009 % w/v) SDS and the use of MucilAir™ as a relevant model for airway toxicity studies.
本研究旨在使用多种体外检测方法评估模型刺激性物质十二烷基硫酸钠(SDS)(≤10mM(0.29%,w/v))对体外气道模型 MucilAir™ 的影响。还探索了 MucilAir™ 在恢复研究中的应用。24 小时暴露可使 SDS 浓度≥0.63mM(0.018%,w/v)时的 IL-8 释放增加。在 SDS 浓度≥1.25mM(0.04%,w/v)时,粘蛋白分泌增加,跨上皮电阻(TEER)降低。在 SDS 浓度≥2.5mM(0.07%,w/v)时观察到细胞毒性(细胞培养液中乳酸脱氢酶(LDH)释放)。检测方法的灵敏度为 IL-8 释放>TEER>粘蛋白分泌>LDH 释放。7 天后,所有检测方法在 SDS 中间浓度下均观察到完全或部分恢复,但在 5mM 和 10mM SDS 下则未观察到。在这些浓度下,形态学观察到侵蚀和细胞丢失。7 天时,Resazurin 代谢在 SDS 浓度高于 2.5mM(0.07%,w/v)时呈剂量依赖性下降趋势。综上所述,这些数据支持 SDS 的无观察效应水平为 0.31mM(0.009%w/v),并支持使用 MucilAir™ 作为气道毒性研究的相关模型。