Recent Published Articles

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


Yang Song , Jing Liu , Lecong Zhang , Fang Xu , Ping Zhang

DOI:10.1016/j.jes.2023.02.004

Received November 02, 2022,Revised , Accepted February 03, 2023, Available online February 13, 2023

Volume 36,2024,Pages 144-154

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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