Bioactive Molecules Research Group, Doctoral School of Science and Technology, Research Platform for Environmental Science, Lebanese University, Lebanon.
Biopharm Drug Dispos. 2013 Apr;34(3):186-94. doi: 10.1002/bdd.1836. Epub 2013 Feb 25.
To better understand the factors that contribute to the accumulation of unmetabolized parabens (p-hydroxybenzoic acid esters) in breast cancer tissue, the binding of a series of parabens (methyl-, ethyl-, butyl-, benzyl-paraben) to human serum albumin (HSA) was investigated by fluorescence spectroscopy and also their ability to modify the binding parameters of albumin site markers. Emission spectra of HSA upon fluorescence excitation of Trp 214 residue at 295 nm were recorded at different molar ratios of PB/HSA and data were corrected for the inner-filter effect. A significant inner-filter effect was obtained for molar ratios of 2.0 and above. For lower molar ratios, a slight increase in fluorescence of HSA was detected. p-Hydroxybenzoic acid, the main metabolite of parabens, did not modify the fluorescence of HSA whatever the molar ratio used. Binding parameters for compounds that are markers of site I, bilirubin and warfarin, were determined in the absence and presence of methyl, butyl and benzyl paraben at molar ratios of PB/HSA of 0, 1 and 2. No variation of the binding constants of these markers was observed. The results indicate that parabens weakly interact with HSA thus suggesting that they are in a free form in blood and therefore more available to reach tissues.
为了更好地了解导致未代谢的对羟基苯甲酸酯（对羟基苯甲酸酯）在乳腺癌组织中积累的因素，通过荧光光谱法研究了一系列对羟基苯甲酸酯（甲基、乙基、丁基、苄基对苯二甲酸酯）与人血清白蛋白（HSA）的结合情况，以及它们修饰白蛋白结合位点标记物结合参数的能力。在 295nm 处荧光激发色氨酸 214 残基时，记录了 HSA 的发射光谱，在不同的 PB/HSA 摩尔比下进行了数据校正，以消除内滤效应。当摩尔比为 2.0 及以上时，会得到显著的内滤效应。对于较低的摩尔比，检测到 HSA 的荧光略有增加。对羟基苯甲酸，对羟基苯甲酸酯的主要代谢物，无论使用的摩尔比如何，都不会修饰 HSA 的荧光。在 PB/HSA 摩尔比为 0、1 和 2 的情况下，确定了作为位点 I 标记物的胆红素和华法林的结合参数。这些标记物的结合常数没有变化。结果表明，对羟基苯甲酸酯与 HSA 弱相互作用，因此表明它们在血液中处于游离状态，因此更有可能到达组织。
