Hazard assessment of beta-lactams: Integrating in silico and QSTR approaches with in vivo zebrafish embryo toxicity testing
Hazard assessment of beta-lactams: Integrating in silico and QSTR approaches with in vivo zebrafish embryo toxicity testing
复制标题
β-内酰胺的危害评估：将计算机和 QSTR 方法与体内斑马鱼胚胎毒性测试相结合
DOI：
10.1016/j.ecoenv.2021.113106
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发表时间：
2022
影响因子：
6.8
通讯作者：
Changqin Hu
中科院分区：
文献类型：
--
作者：
Ying Han;Yuanyuan Ma;Bo Chen;Jingpu Zhang;Changqin Hu
抗生素由于其潜在的毒性而引起公共健康和环境问题，已成为药物和个人护理产品（PPCP）的众所周知的代表。β-内酰胺类抗生素是世界上最常用的抗生素。本研究利用斑马鱼胚胎评价β-内酰胺类药物的毒性。结果表明，23种β-内酰胺类化合物均能引起小鼠的畸形和死亡，并呈浓度-效应关系。建立了β-内酰胺类化合物对斑马鱼毒性的定量结构-毒性关系（QSTR）模型，并进行了验证。这些模型在预测β-内酰胺类药物急性毒性方面表现良好且速度快。结构解释表明，β-内酰胺环、噻唑烷/二氢噻嗪环、侧链和空间构型是导致β-内酰胺毒性的主要因素。本课题组前期研究和本次研究的结果也表明，β-内酰胺类药物及其降解产物引起的潜在生物学风险不容忽视。本研究为β-内酰胺类抗生素的环境风险评价和监管提供了重要数据。
Antibiotics have emerged as a well-known representative of pharmaceuticals and personal care products (PPCPs) by causing public health and environmental problems due to their potential toxicity. β-lactams are the most commonly used antibiotics in the world. This study used zebrafish embryos to evaluate the toxicity of β-lactams. The results showed that 23 β-lactam compounds induced malformation and death in a concentration–response manner. Moreover, this study established and validated quantitative structure–toxicity relationship (QSTR) models for the toxicity of β-lactams in zebrafish. These models performed well and fast in the prediction of the acute toxicity of β-lactams. Structural interpretation indicated that the β-lactam ring, the thiazolidine/dihydrothiazine rings, the side chains, and spatial configuration are the main factors responsible for the toxicity of β-lactams. The results from our previous studies and this study also revealed that the potential biological risks caused by β-lactams and their degradation products could not be ignored. This study provided important data for further environmental risk assessment of β-lactams and regulatory purposes.