The influence of different α-sympathomimetic drugs and Benzalkoniumchlorid on the ciliary beat frequency of in vitro cultured human nasal mucosa cells
The influence of different α-sympathomimetic drugs and Benzalkoniumchlorid on the ciliary beat frequency of in vitro cultured human nasal mucosa cells
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DOI：
10.1055/s-2007-966891
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发表时间：
2008-01-01
影响因子：
1
通讯作者：
Stennert, E.
中科院分区：
文献类型：
--
作者：
Mickenhagen, A.;Siefer, O.;Stennert, E.
背景资料：一个适当的体外模型的人鼻粘膜的开发，它允许测量不同的药物物质的影响，对纤毛搏动频率（CBF）在标准化conditions.Method：本研究描述的α-拟交感神经药物萘甲唑啉，赛洛唑啉和羟甲唑啉作为纯物质和防腐剂苯扎氯铵浓度上升对CBF的影响。对于这些调查的人细胞的人鼻粘膜进行了培养，表现出高的恒定性，在平衡测量超过至少200 minutes.Results：的α-拟交感神经药物羟甲唑啉的浓度为0.01%和0.001%，以及萘甲唑啉在所有三个浓度内没有显示任何变化的CBF。而0.1%的赛洛唑啉引起CBF极显著降低。然而，这种CBF的降低在冲洗后部分可逆。羟甲唑林浓度为0.1%时也显示CBF显着降低。然而，这种影响是不可逆的冲洗后，与无底物培养基，但相反，显示了进一步降低CBF。防腐剂苯扎氯铵在浓度为0.005%时就能产生不可逆的纤毛抑制活性。结论：在所研究的三种拟交感神经药物中，只有萘甲唑林在所有测量浓度下均未表现出任何毒性作用。就其治疗应用而言，浓度为0.001%-0.1%的该药物应优于所有其他拟交感神经药物。0.01%和0.001%的羟甲唑啉也无毒性作用。然而，它在0.1%的浓度下对纤毛造成不可逆的损伤。这一点应考虑应用神经病学药物，特别是儿童。赛洛唑啉需要同样的注意，在0.1%的浓度下引起CBF的高度显著释放，这仅是部分可逆的。根据本研究的结果，强烈建议不要使用所有含有防腐剂苯扎氯铵的神经病学药物。
Background: An appropriate in-vitro model of the human nasal mucosa was developed, which allowed to measure the influence of different pharmaceutical substances on the ciliary beat frequency (CBF) under standardized conditions.Method: The present study describes the effect of the alpha-sympathornimetic drugs naphazolin, xylometazolin and oxymetazolin as pure substances and the preservative Benzalkonium chloride in rising concentrations on the CBF. For these investigations human cells of the human nasal mucosa were cultured, which exhibited a high constancy during the equilibration measurements over at least 200 minutes.Results: The a-sympathomimetic drugs oxymetazoline in the concentration of 0.01% and 0.001% as well as naphazoline within all three concentrations did not show any change of the CBF. Whereas xylometazoline in the concentration of 0.1% caused a high-significant decrease of the CBF. This decrease of the CBF was however partially reversible after rinsing out. Oxymetazolin showed likewise a significant decrease of the CBF in the concentration of 0.1%. This effect however was not reversible after rinsing out with substrate-free medium, but on the contrary showed up a further decrease of CBF. The preservative benzalkonium chloride effected an irreversible ciliostatic activity already in the concentration of 0.005%.Conclusions: From the three investigated a-sympathomimetic drugs only naphazoline in all measured concentrations did not show any toxic effect. With regard to its therapeutic application this drug in the concentrations 0.001%-0.1% should be preferred to all other (x-sympathomimetic drugs. Oxymetazoline in the concentration of 0.01% and 0.001% had no toxic effect as well. It however caused an irreversible damage to the cilia in the concentration of 0.1%. This should be considered for the application of rhinological drugs especially in children. The same attention is demanded for xylometazoline, causing a high significant release of CBF in the concentration of 0.1%, which is only partially reversible. Due to the results of this study it has strongly to be advised against the use of all rhinological drugs containing the preservative benzalkonium chloride.