Hepatotoxicity of Three Common Liquid Crystal Monomers in <i>Mus musculus</i>: Differentiation of Actions Across Different Receptors and Pathways
Zhichao Zhang, Shengjie Yuan, Zhongchao Yang, Yafeng Liu, Su Liu, Ling Chen, Bing Wu
Abstract
Liquid crystal monomers (LCMs) of different chemical structures were widely detected in various environmental matrices. However, their health risk evaluation is lacking. Herein, three representative LCMs were selected from 74 LCM candidates upon literature review and acute cytotoxicity evaluation, then Mus musculus were exposed to the three LCMs for 42 days at doses of 0.5 and 50 μg/kg/d to investigate hepatotoxicity and mechanisms. Phenotypic and histopathological results showed that the three LCMs (DTMDPB, MeO3bcH, and 5OCB) induced hepatomegaly, and only 5OCB induced fatty liver. DTMDPB and MeO3bcH decreased the total cholesterol (TCHO) and triglyceride (TG) content, whereas 5OCB increased the TCHO, TG, and alanine aminotransferase levels. Transcriptome and molecular docking analysis revealed that DTMDPB induced hepatotoxicity by agonizing the farnesoid X receptor, resulting in the disruption of unsaturated fatty acid biosynthesis, ascorbic acid and antioxidant pathways, and circadian clock homeostasis. MeO3bcH promoted inflammation and altered unsaturated fatty acid, primary bile acid biosynthesis, and circadian rhythm by antagonizing the aryl hydrocarbon receptor. 5OCB antagonized peroxisome proliferator-activated receptors, leading to fatty liver caused by the disruption of steroid, cholesterol, and terpenoid backbone biosynthesis pathways. This study provides references for understanding the hepatotoxicity of LCMs with different structures and the selection of priority control LCMs.