Chronic administration of triclosan leads to liver fibrosis through hepcidin-ferroportin axis-mediated iron overload  

作　　者：Jing Liu Lecong Zhang Fang Xu Ping Zhang Yang Song 

机构地区：[1]College of Eco-Environmental Engineering,Guizhou Minzu University,Guiyang 550025,China [2]The Institute of Karst Wetland Ecology,Guizhou Minzu University,Guiyang 550025,China [3]State Key Laboratory of Environmental Chemistry and Ecotoxicology,Research Center for Eco-Environmental Sciences,Chinese Academy of Sciences,Beijing 100085,China

出　　处：《Journal of Environmental Sciences》2024年第3期144-154,共11页环境科学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China (No.22166012);Guizhou Provincial Science and Technology Projects (No.[2020]1Z007)。

摘　　要：Triclosan(TCS)has been manufactured as an antibacterial compound for half a century.Currently,it is widely used in various personal care products;however,its potential adverse effects raise a lot of attention.Here,we create a long-term oral administration mouse model and identify the corresponding hepatotoxicity of TCS.We discover that daily intragastric administration of 10 mg/kg TCS to mice for 12 weeks results in severe hepatic fibrosis.Further study displays that hepatic iron increased 18%,23%and 29%upon oral TCS treatment for4,8 and 12 weeks,respectively.Accompanied by hepatic iron variation,splenic and duodenal iron are increased,which indicates systemic iron disorder.Not only excessive iron accumulated in the liver,abnormal hepatic malondialdehyde,prostaglandin synthase 2 and glutathione peroxidase 4 are pointed to ferroptosis.Additional study uncovers that hepcidin expression increases 7%,10%,4%in serum and 2.4-,4.8-,and 2.3-fold on transcriptional levels upon TCS exposure for 4,8 and 12 weeks,individually.Taken together,the mice in the TCS-treated group show disordered systemic iron homeostasis via the upregulated hepatic hepcidin-ferroportin axis.Meanwhile,both hepatic iron overload(systemic level)and hepatocyte ferroptosis(cellular level)are accused of TCS-induced liver fibrosis.Ferriprox■,an iron scavenger,significantly ameliorates TCS-induced liver fibrosis.In summary,this study confirms the impact of TCS on liver fibrosis;a critical signal pathway is also displayed.The significance of the current study is to prompt us to reevaluate the“pros and cons”of TCS applications.

关 键 词：TRICLOSAN Iron metabolism HEPCIDIN HEPATOTOXICITY Liver fibrosis 

分 类 号：X503[环境科学与工程—环境工程]