基于斑马鱼胚胎模型对二苯甲酮类紫外线吸收剂的安全性研究  

Safety of Benzophenone Ultraviolet Light Filters Based on Zebrafish Embryo Model

作　　者：柳亚锋 李媛 张靖雯 陈佳志 谢珍茗[2] 付向荣 Liu Yafeng;Li Yuan;Zhang Jingwen;Chen Jiazhi;Xie Zhenming;Fu Xiangrong(Institute of Chemical Engineering,Guangdong Academy of Sciences,Guangzhou 510665,China;Guangdong University of Technology,Guangzhou 510006,China;Ruyuan Yao Autonomous County Employment Service Administration Bureau,Shaoguan 512600,China)

机构地区：[1]广东省科学院化工研究所,广东广州510665 [2]广东工业大学,广东广州510006 [3]广东省韶关市乳源瑶族自治县就业服务管理局,广东韶关512600

出　　处：《广东化工》2024年第22期76-79,共4页Guangdong Chemical Industry

基　　金：广东省基础与应用基础研究基金项目(2022A1515012584);广东省科学院打造综合产业技术创新中心行动专项(2022GDASZH-2022010105,2023GDASZH-2023010103);天然功效化妆品及原料研发与应用(2024000216)。

摘　　要：本研究通过体外透皮实验评价二苯甲酮类紫外线吸收剂(BPs)的透皮吸收性能,并利用斑马鱼胚胎模型评价BPs的急性毒性和刺激性,结合实验结果和分子对接技术评估二苯甲酮类紫外线吸收剂对斑马鱼胚胎的潜在毒性作用。方法:通过改良Franz扩散池装置,以猪背腹部皮肤为模型,模拟使用条件,评价BPs的经皮吸收性能,利用HPLC分析BPs皮肤沉积量及皮肤透过量;通过观察并记录斑马鱼胚胎心跳情况及不同给药时间和不同给药浓度下斑马鱼胚胎自旋运动次数,评价BPs的急性毒性和刺激性;利用分子对接技术计算皮肤中与急性毒性和刺激性相关靶点结合能,评估BPs的潜在毒性作用。结果:BPs在280nm~340nm具有较好的紫外吸收性能;除BP-4和BP-12外,其他BPs均有部分穿过皮肤进入接收液中,BPs的透皮吸收能力不同;BP-8的LC50值最低,BP-4的LC50值最高;BPs具有一定的刺激性,同等浓度下,BP-4的刺激性是被测药物中最低的;BPs与CYP1A1、CYP1A2、p53通路、炎症介质PGE2、炎症NF-κB通路的四个靶点的结合能相近,与CYP450的亲和力最强,可能是BPs的潜在作用靶点。In this study,the transdermal absorption properties of BPs were evaluated by in vitro transdermal experiment,and the acute toxicity and irritation of BPs were evaluated by zebrafish embryo model.The potential toxic effects of BPs on zebrafish embryo were evaluated by combining experimental results and molecular docking technology.Methods:The transdermal absorption properties of BPs were evaluated by using the modified Franz diffusion cell with pig-back skin as the model,and the skin deposition and skin penetration of BPs were analyzed by HPLC.The acute toxicity and irritability of BPs were evaluated by observing and recording the heartbeat of zebrafish embryo and the number of spin movement of zebrafish embryo.Results:BPs have good UV absorption properties at 280-340 nm.Except for BP-4 and BP-12,the other BPs can partially penetrate the skin and enter the receptor fluid.The permeability of BPs through the skin is different.BP-8 has the lowest LC50 value,while BP-4 has the highest LC50 value.BPs have certain irritation,and the irritation of BP-4 is the lowest among the tested drugs.BPs has similar binding energy with four targets of CYP1A1,CYP1A2,p53 pathway,inflammatory mediator PGE2,and inflammatory NF-κB pathway,and has the strongest affinity with CYP450,which may be a potential target of BPs.

关 键 词：二苯甲酮类 紫外线吸收剂 透皮吸收 斑马鱼胚胎 分子对接 

分 类 号：TQ[化学工程]