The deleterious effects and potential therapeutic strategy of fluorene-9-bisphenol on circadian activity and liver diseases in zebrafish and mice  

作　　者：Shuhui Zhang Xiang Zuo Jialu Luan Huijuan Bai Zhenhua Fu Mingzhu Sun Xin Zhao Xizeng Feng 

机构地区：[1]College of Life Science,State Key Laboratory of Medicinal Chemical Biology,The Key Laboratory of Bioactive Materials,Ministry of Education,Nankai University,Tianjin 300071,China [2]Institute of Robotics&Automatic Information System,College of Artificial Intelligence,Nankai University,Tianjin 300071,China

出　　处：《Journal of Environmental Sciences》2024年第11期13-27,共15页环境科学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.62027812);Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJSYXZDXK006);Tianjin Municipal Bureau of Public Health(No.RC20037).

摘　　要：Increasing evidence indicates that disturbance of the clock genes,which leads to systemic endocrine perturbation,plays a crucial role in the pathogenesis of metabolic and liver diseases.Fluorene-9-bisphenol(BHPF)is utilized in the manufacturing of plastic materials but its biological effects on liver homeostasis remain unknown.The impacts and involved mechanisms of BHPF on the liver diseases,metabolism,and circadian clock were comprehensively studied by zebrafish andmouse models.The therapeutic effect of melatonin(MT)was also verified.Zebrafish and mousemodels with either acute exposure(0.5 and 1μmol/L,1-4 days post-fertilization)or chronic oral exposure(0.5 and 50 mg/(kg·2 days),30 days)were established with various BHPF concentrations.Herein,we identified a crucial role for estrogenic regulation in liver development and circadian locomotor rhythms damaged by BHPF in a zebrafish model.BHPF mice showed chaos in circadian activity through the imbalance of circadian clock component Brain and Muscle Aryl hydrocarbon receptor nuclear translocator-like 1 in the liver and brain.The liver sexual dimorphic alteration alongwith reduced growth hormone and estrogens played a critical role in damaged glucose metabolism,hepatic inflammation,and fibrosis induced by BHPF.Besides,sleep improvement by exogenous MT alleviated BHPF-related glucose metabolism and liver injury in mice.We proposed the pathogenesis of metabolic and liver disease resulting from BHPF and promising targeted therapy for livermetabolism disorders associated with endocrine perturbation chemicals.These results might play a warning role in the administration of endocrine-disrupting chemicals in everyday life and various industry applications.

关 键 词：Fluorene-9-bisphenol(BHPF) MELATONIN Circadian activity Endocrine perturbation Liver diseases Female behavior Hepatic sexual dimorphism 

分 类 号：X171.5[环境科学与工程—环境科学]