海西定
铁转运蛋白
肝纤维化
丙二醛
纤维化
医学
内科学
去铁胺
脂质运载蛋白
内分泌学
药理学
氧化应激
贫血
作者
Jing Liu,Lecong Zhang,Fang Xu,Ping Zhang,Yang Song
标识
DOI:10.1016/j.jes.2023.02.004
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 for 4, 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.
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