UCIBIO, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Portugal.
Synchrotron SOLEIL, L'Orme des Merisiers, Saint Aubin, BP48, 91192, Gif-sur-Yvette, France.
Biochim Biophys Acta Biomembr. 2017 May;1859(5):803-812. doi: 10.1016/j.bbamem.2017.01.031. Epub 2017 Feb 1.
Amoxicillin is a worldwide used antibiotic, and it is classified as a first-line drug against Helicobacter pylori gastric infections. However, the current treatment of these infections has several limitations, such as the side effects and the low therapeutic compliance. Amoxicillin has been associated with gastrointestinal and renal side effects, with higher toxicity when the pH is lower. By considering this association and the well-known pH gradient of the gastric mucosa, this work aims to evaluate the influence of pH on the toxicity of amoxicillin. For that purpose, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) monolayers were used since phosphatidylcholines are the most common phospholipid headgroup of biological membranes. To have insight of the effects of amoxicillin, different techniques were employed, namely, isotherm measurements, infrared reflection-absorption spectroscopy, grazing incident X-ray diffraction and Brewster angle microscopy. The monolayers of DPPC spread onto different buffer solutions (pH1.2, pH5 and pH7.4) showed different structural and packing properties. The interaction with amoxicillin also depended on the pH. At pH7.4, the highest effect was visualized at lower pressures, with partial restoration of the biophysical properties of the monolayer at 30 mN.m. A higher perturbation is shown at acidic pH, in which pores were visualized by Brewster angle microscopy. These perturbations may ultimately be related with amoxicillin toxicity.
阿莫西林是一种全球范围内使用的抗生素，被归类为治疗幽门螺杆菌胃部感染的一线药物。然而，目前这些感染的治疗存在一些局限性，如副作用和治疗顺应性低。阿莫西林与胃肠道和肾脏副作用有关，当 pH 值较低时毒性更高。考虑到这种关联以及胃黏膜众所周知的 pH 梯度，本工作旨在评估 pH 值对阿莫西林毒性的影响。为此，使用了 1,2-二棕榈酰基-sn-甘油-3-磷酸胆碱（DPPC）单层膜，因为磷脂酰胆碱是生物膜中最常见的磷脂头部基团。为了深入了解阿莫西林的影响，采用了多种技术，即等温测量、红外反射吸收光谱、掠入射 X 射线衍射和布鲁斯特角显微镜。在不同缓冲溶液（pH1.2、pH5 和 pH7.4）上展开的 DPPC 单层膜显示出不同的结构和堆积特性。与阿莫西林的相互作用也取决于 pH 值。在 pH7.4 时，在较低的压力下观察到最高的效果，在 30 mN.m 时单层膜的生物物理性质部分得到恢复。在酸性 pH 值下显示出更高的扰动，在那里可以通过布鲁斯特角显微镜观察到孔。这些扰动最终可能与阿莫西林的毒性有关。
