Combined cytotoxicity of phthalate esters on HepG2 cells: A comprehensive analysis of transcriptomics and metabolomics

文献类型： 外文期刊

第一作者： Dong, Yanjie

作者： Dong, Yanjie;Cai, Da;Zhao, Shancang;Wang, Lei;Liu, Chao

作者机构：

关键词： Dibutyl phthalate; Combined cytotoxicity; Metabolomics profiling; Transcriptomics analysis; HepG2 cell; bis(2-ethylhexyl) phthalate

期刊名称：FOOD AND CHEMICAL TOXICOLOGY （ 影响因子：4.3； 五年影响因子：5.1 ）

ISSN： 0278-6915

年卷期： 2023 年 180 卷

页码：

收录情况： SCI

摘要： Phthalate esters (PAEs), widely used as plasticizers, may pose a potential environmental and human hazard. The aim of this study was to compare the cytotoxicity of di(2-ethylhexyl) phthalates (DEHP) and dibutyl phthalate (DBP)) after their exposure to HepG2 cells alone or in combination. HepG2 cells treated with individual/combined DEHP and DBP at a dose of 10-2 M for 24 h were selected for metabolome and transcriptome analysis. The results demonstrated that exposure to the mixtures of DEHP and DBP caused enhanced or reduced toxic effects regarding 8 pathways with 1065 downregulated genes and 643 upregulated genes, in comparison with those of single chemicals. The combined toxicity of mixture revealed both synergistic and antagonistic interactions between DEHP and DBP. Besides, combined exposure to DEHP and DBP promoted TCA cycle, pyrimidine, and purine metabolism, while an antagonistic effect on fatty acid derangement should require further investigation. To summarize, our results suggest that DEHP exposed alone or combined with DBP caused a variety of metabolic disorders, and the type of combination effects varied among metabolic pathways.

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