Hepatotoxicity of Three Common Liquid Crystal Monomers in Mus musculus: Differentiation of Actions Across Different Receptors and Pathways

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.