Novel Organophosphate Ester Tris(2,4-di-tert-butylphenyl)phosphate Alters Lipid Metabolism: Insights from Lipidomic Analysis and mRNA Expression.

IF 3.7 3区医学 Q2 CHEMISTRY, MEDICINAL

Chemical Research in Toxicology Pub Date : 2025-02-10 DOI:10.1021/acs.chemrestox.4c00460

Pingping Kang, Qianyu Chen, Jia Wu, Qi Zhang, Doug Crump, Guanyong Su

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引用次数: 0

Abstract

Tris(2,4-di-tert-butylphenyl)phosphate (TDTBPP), a novel organophosphate ester (OPE), has been extensively detected in various environmental and biological samples; however, its potential biological effects remain unexplored. In this study, we investigated biotransformation characteristics, alteration of lipid metabolism, and mRNA expression in primary mouse hepatocytes (PMHs) following exposure to TDTBPP. After 36-h exposure in PMHs, TDTBPP exhibited a high stability potential with no statistically significant degradation trend. Subsequently, we analyzed the disruption of lipid homeostasis in PMHs following exposure to 0-4.5 μM TDTBPP. Lipidomic analysis indicated that TDTBPP disrupted lipid homeostasis in PMHs, and several lipid classes were dysregulated, in particular, glycerolipids and glycerophospholipids. Additionally, three lipids were proposed as potential lipid biomarkers of TDTBPP exposure, including triglycerides (TGs) and phosphatidylcholines (PCs). These observations were further supported by transcriptional changes, with significant alteration observed in genes associated with lipid uptake, de novo lipogenesis, β-oxidation of fatty acids, glycerolipid metabolism, and lipid export. Overall, these findings highlight the detrimental effects of TDTBPP on lipid homeostasis, providing important insights for health risk assessments of this abundant OPE in the environment.

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来源期刊

Chemical Research in Toxicology 医学-毒理学

CiteScore

7.90

自引率

7.30%

发文量

215

审稿时长

3.5 months

期刊介绍： Chemical Research in Toxicology publishes Articles, Rapid Reports, Chemical Profiles, Reviews, Perspectives, Letters to the Editor, and ToxWatch on a wide range of topics in Toxicology that inform a chemical and molecular understanding and capacity to predict biological outcomes on the basis of structures and processes. The overarching goal of activities reported in the Journal are to provide knowledge and innovative approaches needed to promote intelligent solutions for human safety and ecosystem preservation. The journal emphasizes insight concerning mechanisms of toxicity over phenomenological observations. It upholds rigorous chemical, physical and mathematical standards for characterization and application of modern techniques.