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Estrogen Deficiency Aggravates Fluoride-Induced Liver Damage and Lipid Metabolism Disorder in Rats

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Abstract

Estrogen exerts essential role in liver metabolism, and its deficiency is frequently accompanied by a series of metabolic disorder diseases. To investigate the role of estrogen deficiency in fluorine ions (F–) induced liver injury, the ovariectomy (OVX) rat models were performed by surgically removing the ovaries, and the rats from OVX and non-OVX models were exposed to differential dose of F– (0, 25, 50 and 100 mg/L) in drinking water for 90 days. The liver morphological structure was evaluated by hematoxylin–eosin staining. Proliferation ability of hepatocytes was evaluated by 5-bromo-2-deoxyuridine (BrdU) assay. And distribution of lipid droplets in liver tissue was observed via oil red O staining. In addition, the liver function and lipid metabolism parameters in serum were detected by commercial kits. Results showed that F– induced hepatocytes morphological damage and inhibited the proliferation ability of hepatocytes; estrogen deficiency exacerbated these changes. The deposition of lipid droplets in the liver tissue was multiplicative with increased F– dose, especially after estrogen deficiency. In addition, F– exposure increased (P < 0.05 or P < 0.01) serum aminotransferase (ALT), aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transpeptidase (γ-GT) activities and total bilirubin (T-bil) level; meanwhile, serum triglyceride (TG) and cholesterol (TC) levels were also elevated (P < 0.05 or P < 0.01). F–-induced liver function and lipid metabolism indexes were further increased (P < 0.05 or P < 0.01) in the state of estrogen deficiency. In conclusion, estrogen deficiency aggravated F–-induced liver damage and lipid metabolism disorder.

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Funding

This work is supported by the China National Nature Science Foundation (Grant No. 31201963) and the Natural Science Foundation of Henan (Grant No. 202300410120).

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Authors and Affiliations

  1. College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, 471023, Henan, People’s Republic of China

    Ya-ming Yu, Bian-hua Zhou, Yi-lin Yang, Cheng-Xiang Guo, Jing Zhao & Hong-wei Wang

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  1. Ya-ming Yu
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  2. Bian-hua Zhou
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  3. Yi-lin Yang
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Contributions

YY: Performing the experiments, writing the initial draft, preparation of the data presentation. BZ: Acquisition of the financial support for the psroject leading to this publication, critical review, provision of resources. YY: Performing the experiments. CXG: Performing the experiments. JZ: Supervision, HW: Ideas, creation of models, funding acquisition.

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Correspondence to Bian-hua Zhou.

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Yu, Ym., Zhou, Bh., Yang, Yl. et al. Estrogen Deficiency Aggravates Fluoride-Induced Liver Damage and Lipid Metabolism Disorder in Rats. Biol Trace Elem Res 200, 2767–2776 (2022). https://doi.org/10.1007/s12011-021-02857-1

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