Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
Exp Eye Res. 2020 Jul;196:108057. doi: 10.1016/j.exer.2020.108057. Epub 2020 May 5.
Recently, we discovered that the cosmetic preservatives, benzalkonium chloride and formaldehyde, are especially toxic to human meibomian gland epithelial cells (HMGECs). Exposure to these agents, at concentrations approved for human use, leads within hours to cellular atrophy and death. We hypothesize that these effects are not unique, and that other cosmetic preservatives also exert adverse effects on HMGECs. Such compounds include parabens, phenoxyethanol and chlorphenesin, which have been reported to be toxic to corneal and conjunctival epithelial cells, the liver and kidney, as well as to irritate the eye. To test our hypothesis, we examined the influence of parabens, phenoxyethanol and chlorphenesin on the morphology, signaling, survival, proliferation and lipid expression of immortalized (I) HMGECs. These cells were cultured under proliferating or differentiating conditions with varying concentrations of methylparaben, ethylparaben, phenoxyethanol and chlorphenesin for up to 5 days. We monitored the signaling ability, appearance, number and neutral lipid content of the IHMGECs, as well as their lysosome accumulation. Our findings show that a 30-min exposure of IHMGECs to these preservatives results in a significant reduction in the activity of the Akt pathway. This effect is dose-dependent and occurs at concentrations equal to (chlorphenesin) and less than (all others) those dosages approved for human use. Further, a 24-h treatment of the IHMGECs with concentrations of methylparaben, ethylparaben, phenoxyethanol and chlorphenesin close to, or at, the approved human dose induces cellular atrophy and death. At all concentrations tested, no preservative stimulated IHMGEC proliferation. Of particular interest, it was not possible to evaluate the influence of these preservatives, at close to human approved dosages, on IHMGEC differentiation, because the cells did not survive the treatment. In summary, our results support our hypothesis and show that methylparaben, ethylparaben, phenoxyethanol and chlorphenesin are toxic to IHMGECs.
最近，我们发现化妆品防腐剂苯扎氯铵和甲醛对人睑板腺上皮细胞（HMGECs）特别有毒。在数小时内，暴露于这些在批准用于人体的浓度下的试剂会导致细胞萎缩和死亡。我们假设这些影响不是独特的，其他化妆品防腐剂也会对 HMGECs 产生不良影响。这些化合物包括对羟基苯甲酸酯、苯氧乙醇和氯苯甘醚，它们已被报道对角膜和结膜上皮细胞、肝脏和肾脏有毒，并且会刺激眼睛。为了检验我们的假设，我们研究了对羟基苯甲酸酯、苯氧乙醇和氯苯甘醚对永生化（I）HMGECs 的形态、信号、存活、增殖和脂质表达的影响。这些细胞在增殖或分化条件下，用不同浓度的甲基对羟基苯甲酸酯、乙基对羟基苯甲酸酯、苯氧乙醇和氯苯甘醚培养长达 5 天。我们监测了 IHMGECs 的信号能力、外观、数量和中性脂质含量，以及溶酶体积累。我们的发现表明，IHMGECs 暴露于这些防腐剂 30 分钟会导致 Akt 途径的活性显著降低。这种作用是剂量依赖性的，发生在等于（氯苯甘醚）和小于（其他所有）批准用于人体的剂量。此外，用接近或等于批准人体剂量的浓度用甲基对羟基苯甲酸酯、乙基对羟基苯甲酸酯、苯氧乙醇和氯苯甘醚处理 IHMGECs 24 小时会诱导细胞萎缩和死亡。在所有测试的浓度下，没有防腐剂刺激 IHMGEC 增殖。特别值得注意的是，由于细胞无法在治疗后存活，因此无法评估这些防腐剂在接近人体批准剂量下对 IHMGEC 分化的影响。总之，我们的结果支持我们的假设，并表明甲基对羟基苯甲酸酯、乙基对羟基苯甲酸酯、苯氧乙醇和氯苯甘醚对 IHMGECs 有毒。
