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
柳亚锋 1李媛 1张靖雯 1陈佳志 1谢珍茗 2付向荣3
作者信息
- 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
- 折叠
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 280 nm～340 nm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.
Abstract
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Key words
Benzophenones/ultraviolet absorber/Transdermal absorption/Zebrafish embryo/molecular docking引用本文复制引用
出版年
2024
NETL
NSTL
万方数据