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Ziziphus spina-christi leaf extract attenuates mercuric chloride-induced liver injury in male rats via inhibition of oxidative damage

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Abstract

Heavy metal contamination including mercury (Hg) has become one of the most serious environmental problems facing humans and other living organisms. Here, the hepatoprotective effects of Z. spina-christi leaf extract (ZCE) against inorganic mercury salt (mercuric chloride; HgCl2)–induced hepatotoxicity model was investigated in rats. Mercury concentration, liver function markers, oxidative stress markers, inflammation, cell death indicators, and histopathology were assessed. ZCE protected against HgCl2-induced hepatotoxicity, decreased Hg concentration, lipid peroxidation, and nitric oxide, increased glutathione, superoxide dismutase, catalase, and glutathione recycling enzymes (peroxidase and reductase), and upregulated nuclear factor-erythroid 2-related factor 2 (Nrf2) gene expression in HgCl2-intoxicated rat hepatic tissue. Nrf2 downstream gene and heme oxygenase-1 were also upregulated, confirming that hepatoprotection by ZCE against HgCl2-induced liver damage involved activation of the Nrf2/antioxidant response element pathway. ZCE also decreased the expression and production of pro-inflammatory cytokines and pro-apoptotic proteins and increased anti-apoptotic protein Bcl-2. Immunohistochemical analysis of liver tissues of HgCl2-treated rats confirmed the alternations of apoptotic-related protein expression. Our data demonstrated that post-administration of ZCE attenuated HgCl2-induced liver damage by activating the Nrf2/HO-1 signaling pathway. Therefore, administering this extract may be a novel therapeutic strategy for inorganic mercury intoxication.

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Funding

The authors would like to extend their sincere appreciation to the Researchers Supporting Project number: RSP-2020/96, King Saud University, Riyadh, Saudi Arabia.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Helwan University, Cairo, Egypt

    Shimaa S. Ramadan

  2. Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia

    Rafa S. Almeer, Saad Alkahtani, Saud Alarifi & Gadah Albasher

  3. Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt

    Ahmed E. Abdel Moneim

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  1. Shimaa S. Ramadan
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  2. Rafa S. Almeer
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  3. Saad Alkahtani
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  4. Saud Alarifi
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  5. Gadah Albasher
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  6. Ahmed E. Abdel Moneim
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Contributions

Saad Alkahtani, Saud Alarifi, and Gadah Albasher: data curation, resources, validation, writing—original draft. Rafa S. Almeer: conceptualization, data curation, writing—original draft, supervision, resources, validation. Shimaa S. Ramadan: investigation, writing—review and editing. Ahmed E. Abdel Moneim: conceptualization, methodology, data curation, writing—original draft, visualization, investigation, supervision, writing—review and editing

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Correspondence to Rafa S. Almeer.

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All procedures were approved by the Committee of Research Ethics for Laboratory Animal Care, Faculty of Science, Helwan University (approval no. HU2018/Z/011-3).

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Ramadan, S.S., Almeer, R.S., Alkahtani, S. et al. Ziziphus spina-christi leaf extract attenuates mercuric chloride-induced liver injury in male rats via inhibition of oxidative damage. Environ Sci Pollut Res 28, 17482–17494 (2021). https://doi.org/10.1007/s11356-020-12160-6

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