Liver Fibrosis Can Be Induced by High Salt Intake through Excess Reactive Oxygen Species (ROS) Production

Guang Wang, Cheung Kwan Yeung, Wing Yan Wong, Nuan Zhang, Yi Fan Wei, Jing Li Zhang, Yu Yan, Ching Yee Wong, Jun Jie Tang, Manli Chuai, Kenneth Ka Ho Lee, Li Jing Wang, Xuesong Yang (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    33 Citations (Scopus)


    High salt intake has been known to cause hypertension and other side effects. However, it is still unclear whether it also affects fibrosis in the mature or developing liver. This study demonstrates that high salt exposure in mice (4% NaCl in drinking water) and chick embryo (calculated final osmolality of the egg was 300 mosm/L) could lead to derangement of the hepatic cords and liver fibrosis using H&E, PAS, Masson, and Sirius red staining. Meanwhile, Desmin immunofluorescent staining of mouse and chick embryo livers indicated that hepatic stellate cells were activated after the high salt exposure. pHIS3 and BrdU immunohistological staining of mouse and chick embryo livers indicated that cell proliferation decreased; as well, TUNEL analyses indicated that cell apoptosis increased in the presence of high salt exposure. Next, dihydroethidium staining on the cultured chick hepatocytes indicated the excess ROS was generated following high salt exposure. Furthermore, AAPH (a known inducer of ROS production) treatment also induced the liver fibrosis in chick embryo. Positive Nrf2 and Keap1 immunohistological staining on mouse liver suggested that Nrf2/Keap1 signaling was involved in high salt induced ROS production. Finally, the CCK8 assay was used to determine whether or not the growth inhibitory effect induced by high salt exposure can be rescued by antioxidant vitamin C. Meanwhile, the RT-PCR result indicated that the Nrf2/Keap1 downsteam genes including HO-1, NQO-1, and SOD2 were involved in this process. In sum, these experiments suggest that high salt intake would lead to high risk of liver damage and fibrosis in both adults and developing embryos. The pathological mechanism may be the result from an imbalance between oxidative stress and the antioxidant system.

    Original languageEnglish
    Pages (from-to)1610-1617
    Number of pages8
    JournalJournal of Agricultural and Food Chemistry
    Issue number7
    Early online date4 Feb 2016
    Publication statusPublished - 24 Feb 2016


    • chick embryos
    • high salt
    • liver fibrosis
    • mouse
    • ROS

    ASJC Scopus subject areas

    • General Agricultural and Biological Sciences
    • General Chemistry


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