Liang Shengxian, Zhang Yue, Bo Haimei, Duan Wenzhao, Zhong Li
Institute of Life Sciences and Green Development, College of Life Sciences, Hebei University, Baoding 071000, China.
Institute of Life Sciences and Green Development, College of Life Sciences, Hebei University, Baoding 071000, China.
Ecotoxicol Environ Saf. 2023 Jan 15;250:114478. doi: 10.1016/j.ecoenv.2022.114478. Epub 2022 Dec 29.
The widespread high concentrations of benzotriazole ultraviolet stabilizers (BUVSs) in many biotic and abiotic samples have raised urgent concerns of their adverse effects on environmental and human health. In this study, we investigated the toxicity of three typical BUVSs (UV-328, UV-329, UV-P) with HepG2 cells in vitro. Results indicated that the three BUVSs showed weak cytotoxicity in HepG2 cells at concentrations lower than 50 μM. Transcriptional analysis indicated that the toxic effects of the three chemicals followed the order of UV-P > UV-329 > UV-328. UV-P and UV-329 may act as potential environmental diabetogens by significantly enriching several diabetic related items in both GO and KEGG analysis. Moreover, UV-P and UV-329 significantly upregulated the expression of AHR target genes (CYP1A1, CYP1A2, UGT1A1, etc.), and increased the ethoxyresorufin-O-deethylase (EROD) activity and exhibited agonistic activity toward AHR in the XRE-mediated luciferase reporter gene assay. Molecular docking assay also indicated that UV-329 and UV-P had higher binding affinities to AHR-LBD than UV-328. In brief, our findings indicated that UV-P and UV-329 were potential agonist of AHR ligand, and may exert more toxicity than UV-328 in inducing liver toxicity.
许多生物和非生物样品中广泛存在高浓度的苯并三唑紫外线稳定剂（BUVSs），这引发了人们对其对环境和人类健康不利影响的迫切担忧。在本研究中，我们在体外研究了三种典型的BUVSs（UV-328、UV-329、UV-P）对HepG2细胞的毒性。结果表明，在浓度低于50μM时，这三种BUVSs在HepG2细胞中表现出较弱的细胞毒性。转录分析表明，这三种化学物质的毒性作用顺序为UV-P > UV-329 > UV-328。在基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析中，UV-P和UV-329通过显著富集多个糖尿病相关条目，可能作为潜在的环境致糖尿病因素。此外，在XRE介导的荧光素酶报告基因检测中，UV-P和UV-329显著上调芳烃受体（AHR）靶基因（CYP1A1、CYP1A2、UGT1A1等）的表达，增加乙氧基异吩恶唑酮-O-脱乙基酶（EROD）活性，并对AHR表现出激动活性。分子对接分析还表明，UV-329和UV-P对AHR配体结合域（AHR-LBD）的结合亲和力高于UV-328。简而言之，我们的研究结果表明，UV-P和UV-329是AHR配体的潜在激动剂，在诱导肝毒性方面可能比UV-328具有更大的毒性。
