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双酚衍生物对HepG2细胞潜在毒性作用的计算机模拟与体外比较评估。

Comparative in silico and in vitro evaluation of possible toxic effects of bisphenol derivatives in HepG2 cells.

作者信息

Balci-Ozyurt Aylin, Yirun Anıl, Cakır Deniz Arca, Ozcelik İbrahim, Bacanli Merve, Ozkemahli Gizem, Sabuncuoglu Suna, Basaran Nursen, Erkekoglu Pınar

机构信息

Hacettepe University, Faculty of Pharmacy, Department of Toxicology, Ankara, Turkey.

School of Pharmacy, Department of Toxicology, Bahçeşehir University, Istanbul, Turkey.

出版信息

Toxicol Res (Camb). 2024 Aug 11;13(4):tfae127. doi: 10.1093/toxres/tfae127. eCollection 2024 Aug.

DOI:10.1093/toxres/tfae127
PMID:39132192
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11316955/
Abstract

INTRODUCTION

Bisphenols are widely used in the production of polycarbonate plastics and resin coatings. Bisphenol A (BPA) is suggested to cause a wide range of unwanted effects and "low dose toxicity". With the search for alternative substances to BPA, the use of other bisphenol derivatives namely bisphenol F (BPF) and bisphenol S (BPS) has increased.

METHODS

In the current study, we aimed to evaluate the in silico predicted inhibitory concentration 50s (pIC50s) of bisphenol derivatives on immune and apoptotic markers and DNA damage on HepG2 cells. Moreover, apoptotic, genotoxic and immunotoxic effects of BPA, BPF and BPS were determined comparatively. Effects of bisphenols on apoptosis were evaluated by detecting different caspase activities. The genotoxic effects of bisphenols were evaluated by measuring the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-oxoguanine glycosylase (OGG1). To determine the immunotoxic effect of bisphenol derivatives, the levels of interleukin 4 (IL-4) and interleukin 10 (IL-10), transforming growth factor beta (TGF-β) and tumor necrosis factor-alpha (TNF-α), which are known to be expressed by HepG2 cells, were measured. Results: In silico data indicate that all of the bisphenols may cause alterations in immune and apoptotic markers as well as DNA damage at low doses. İn vitro data revealed that all bisphenol derivatives could affect immune markers at inhibitory concentration 30s (ICs). In addition, BPF and BPS may also have apoptotic immunotoxic effects.

CONCLUSION

Both in silico and in vivo research are needed further to examine the toxic effects of alternative bisphenol derivatives.

摘要

引言

双酚广泛应用于聚碳酸酯塑料和树脂涂料的生产。双酚A(BPA)被认为会引发一系列不良影响和“低剂量毒性”。随着寻找BPA的替代物质,其他双酚衍生物即双酚F(BPF)和双酚S(BPS)的使用有所增加。

方法

在当前研究中,我们旨在评估双酚衍生物对免疫和凋亡标志物的计算机预测半数抑制浓度(pIC50)以及对HepG2细胞的DNA损伤。此外,还比较了BPA、BPF和BPS的凋亡、遗传毒性和免疫毒性作用。通过检测不同的半胱天冬酶活性来评估双酚对凋亡的影响。通过测量8-羟基-2'-脱氧鸟苷(8-OHdG)和8-氧代鸟嘌呤糖基化酶(OGG1)的水平来评估双酚的遗传毒性作用。为了确定双酚衍生物的免疫毒性作用,测量了已知由HepG2细胞表达的白细胞介素4(IL-4)和白细胞介素10(IL-10)、转化生长因子β(TGF-β)和肿瘤坏死因子-α(TNF-α)的水平。结果:计算机数据表明,所有双酚在低剂量时都可能导致免疫和凋亡标志物的改变以及DNA损伤。体外数据显示,所有双酚衍生物在30%抑制浓度(IC30)时都能影响免疫标志物。此外,BPF和BPS也可能具有凋亡免疫毒性作用。

结论

需要进一步开展计算机模拟和体内研究,以检验替代双酚衍生物的毒性作用。

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