Vremere Anton, Merola Carmine, Fanti Federico, Sergi Manuel, Perugini Monia, Compagnone Dario, Mikhail Milena, Lorenzetti Stefano, Amorena Michele
Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Italy; Dpt. of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità - ISS, Rome, Italy.
Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Italy.
Food Chem Toxicol. 2022 Jul;165:113166. doi: 10.1016/j.fct.2022.113166. Epub 2022 May 21.
Oxysterols are cholesterol oxidation products and bioactive lipids involved in developmental signalling pathways, embryonic and postembryonic tissue patterning and homeostasis. The embryonic period is a very sensitive window of exposure to bisphenol A (BPA), hence the role of BPA on the levels of oxysterols in the very early stages of zebrafish embryogenesis is a relevant novel field of investigation.
To compare the role of BPA on oxysterols levels in zebrafish embryos at 8 and 24 h post fertilization (hpf) with cytochromes P450 (CYPs)-modulating chemicals (carbamazepine, ketoconazole, and hydrogen peroxide).
Upon a dose range finding, zebrafish embryos were exposed to environmentally relevant (0.04 μM) and toxicological (17.5 μM) BPA concentrations. Seven oxysterols were profiled by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).
Similarly to the CYPs-modulating chemicals, BPA caused: i) no significant changes at 8 hpf and ii) a dose-dependent increase of total oxysterols at 24 hpf, with 27-hydroxycholesterol as the most regulated oxysterol.
In the first day post-fertilization of the zebrafish embryos, the role of BPA alike a CYPs-modulating chemical was confirmed by the similar oxysterol changes observed with the already known CYPs-modulating chemicals.
氧化甾醇是胆固醇氧化产物和生物活性脂质，参与发育信号通路、胚胎及胚后组织模式形成和体内平衡。胚胎期是暴露于双酚A（BPA）的一个非常敏感的时期，因此BPA对斑马鱼胚胎发育早期氧化甾醇水平的影响是一个相关的新研究领域。
比较BPA与细胞色素P450（CYPs）调节化学物质（卡马西平、酮康唑和过氧化氢）对受精后8小时（hpf）和24小时斑马鱼胚胎氧化甾醇水平的影响。
在确定剂量范围后，将斑马鱼胚胎暴露于环境相关浓度（0.04 μM）和毒理学浓度（17.5 μM）的BPA中。通过高效液相色谱-串联质谱法（HPLC-MS/MS）分析七种氧化甾醇。
与CYPs调节化学物质类似，BPA导致：i）在8 hpf时无显著变化；ii）在24 hpf时总氧化甾醇呈剂量依赖性增加，其中27-羟基胆固醇是受调控最明显的氧化甾醇。
在斑马鱼胚胎受精后的第一天，通过观察到与已知CYPs调节化学物质类似的氧化甾醇变化，证实了BPA与CYPs调节化学物质具有相似的作用。
