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. 2025 Sep 15:303:119054.
doi: 10.1016/j.ecoenv.2025.119054. Online ahead of print.

The role and mechanism of ERalpha(ERα) in atrazine-induced disorders of hepatic iron metabolism

Haotang Zhao  1 , Jiaxin Zhang  1 , Tong Lu  1 , Manting Hou  1 , Yaqin Zheng  1 , Ying Qiao  1 , Xiaotong Wu  1 , Shihao Lou  1 , Yuezhu Zhang  2 , Lin Ye  3
Affiliations

The role and mechanism of ERalpha(ERα) in atrazine-induced disorders of hepatic iron metabolism

Haotang Zhao et al. Ecotoxicol Environ Saf. .

Abstract

Atrazine (ATR), a widely used herbicide, that can affect liver metabolism. This study explored how ATR impacted liver iron metabolism using Wistar rats and L02 cells exposed to ATR. This study revealed that ATR can inhibit the expression of ERα in hepatocytes, the ERα can directly bind to the promoter of Hepcidin to downregulate its expression. ATR exposure caused increased levels of Hepcidin, further decreased the FPN1 expression, resulting in reducing exportation of iron. Moreover, the expression of the genes involved in iron transport, including DMT1, PCBP1, PCBP2 and STEAP3 was decreased, leading to hepatic iron accumulation. While, overexpressing ERα in L02 cells reversed these effects caused by ATR, thus reducing hepatic iron accumulation. The results indicated that ATR can affect liver iron metabolism by inhibiting ERα, further regulating the expression of key moleculars involved in iron metabolism, providing a new insight into revealing the toxic mechanism of ATR.

Keywords: Atrazine; ERα; Hepcidin; Iron metabolism.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yuezhu Zhang reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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