Department of Medical Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-230, Bialystok, Poland.
Department of Medicinal Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-230, Bialystok, Poland.
J Appl Toxicol. 2017 Sep;37(9):1117-1124. doi: 10.1002/jat.3466. Epub 2017 Apr 6.
Parabens owing to their many advantageous properties are widely applied in cosmetics, food products and pharmaceuticals. However, recent research results have shown that they possess the ability to accumulate in the human body and exert many adverse effects. In this study, the impact of methylparaben (MP) as the most frequently used preservative in cosmetics, on human dermal fibroblasts and collagen production was evaluated. In cells treated with 0.01, 0.03 and 0.05% MP a dose-dependent decrease in collagen biosynthesis was revealed, which was positively correlated with the activity of prolidase responsible for the recovery of proline. Consequently, the concentration of total collagen secreted into the medium was markedly diminished. A similar reduction in expression of the major skin collagen type I at both the protein and mRNA level as well as collagen type III and VI at the mRNA level was also detected. The decrease in the collagen level may result not only from the reduced synthesis but also increased degradation owing to MP-induced activation of pro-MMP-2 (72 kDa). The increase in activity of MMP-2 (66 kDa) was accompanied by a reduction in the inhibitory activity of TIMP-2. In addition, an inhibitory effect of MP on cell survival and proliferation was revealed in this study. The increased expression and nuclear translocation of caspase-3 as well as increased Bax and decreased Bcl-2 expression may suggest MP-induced cell apoptosis. In summary, we have provided new data on the adverse effects of methylparaben on human dermal fibroblasts and the main structural protein of the skin. Further studies on the mechanisms responsible for its action are in progress. Copyright © 2017 John Wiley & Sons, Ltd.
由于其许多有利的特性，对羟基苯甲酸酯被广泛应用于化妆品、食品产品和药物中。然而，最近的研究结果表明，它们具有在人体内积累并产生许多不良影响的能力。在这项研究中，评估了化妆品中最常用的防腐剂对羟基苯甲酸甲酯（MP）对人皮肤成纤维细胞和胶原蛋白产生的影响。在 0.01%、0.03%和 0.05%MP 处理的细胞中，胶原蛋白生物合成呈剂量依赖性下降，这与负责脯氨酸恢复的脯氨酸内肽酶的活性呈正相关。因此，分泌到培养基中的总胶原蛋白浓度明显减少。还检测到主要皮肤胶原蛋白 I 在蛋白质和 mRNA 水平以及胶原蛋白 III 和 VI 在 mRNA 水平的表达也呈相似的减少。胶原蛋白水平的降低不仅可能是由于合成减少，还可能是由于 MP 诱导的 pro-MMP-2（72 kDa）的激活导致降解增加。MMP-2（66 kDa）活性的增加伴随着 TIMP-2 抑制活性的降低。此外，本研究还揭示了 MP 对细胞存活和增殖的抑制作用。caspase-3 的表达增加和核转位以及 Bax 的增加和 Bcl-2 的减少表达可能表明 MP 诱导的细胞凋亡。总之，我们提供了对羟基苯甲酸甲酯对人皮肤成纤维细胞和皮肤主要结构蛋白的不良影响的新数据。目前正在对其作用机制进行进一步研究。版权所有 © 2017 约翰威立父子公司
