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Hepatoprotective and neuroprotective effect of taxifolin on hepatic encephalopathy in rats

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Abstract

This study was planned to assess the potential protective effects of taxifolin against thioacetamide-induced hepatic encephalopathy and subsequently to portray its behavioural results. The experimental model was induced with three doses of (200 mg/kg i.p.) thioacetamide and taxifolin (50 and 100 mg/kg, p.o.) was administered for fourteen days. Taxifolin effectively attenuated hepatic encephalopathy through decrease in AST, ALT, ALP and LDH concentrations and improvement of hyperammonemia, and increase in antioxidant capacity by decreasing MDA, ROS, and increasing CAT and GSH. In addition, the expressions of NF-κB, TNF-α, IL-1β, caspase-3 and Bax was down-regulated while IL-10 and Bcl-2 expressions were up-regulated with taxifolin treatment. The recovery was confirmed by downregulation of iNOS and 8-OHdG expressions in our immunohistochemical analysis. Taxifolin treatment reduced the disrupting role of thioacetamide as seen by corrected hyperammonemia as well as preservation of astrocyte and hepatocyte structure. Elevated plus maze and locomotor activity tests also proved that taxifolin might repeal the neurobehavioral disabilities. In conclusion, taxifolin has shown hepatoprotective and neuroprotective roles with antioxidant and anti-inflammatory effects, as well as suppressing the excessive release of ammonia, and it eventually reversed neurobehavioral impairments.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors are grateful to Prof. Dr. Ahmet Hacimuftuoglu for his support during the experiments.

Funding

This work was supported by Research Fund of the Ataturk University. (Project Number: TSA-2019–7527).

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Authors and Affiliations

  1. Medical Pharmacology Department, Faculty of Medicine, Ataturk University, 25100, Erzurum, Turkey

    Ufuk Okkay

  2. Pharmacology Department, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey

    Irmak Ferah Okkay

  3. Physiology Department, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan, Turkey

    Betul Cicek

  4. Pharmacology Department, Faculty of Pharmacy, Erzincan Binali Yildirim University, Erzincan, Turkey

    Ismail Cagri Aydin

  5. Pathology Department, Faculty of Veterinary Medicine, Sivas Cumhuriyet University, Sivas, Turkey

    Mustafa Ozkaraca

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  1. Ufuk Okkay
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Contributions

Ufuk Okkay: Investigation, Methodology, Resources; Writing-original draft, Visualization, Funding acquisition, Writing-review & editing. Irmak Ferah Okkay: Funding acquisition, Data curation, Conceptualization, Validation, Writing-original draft, Writing-review & editing. Betul Cicek: Methodology. Ismail Cagri Aydin: Investigation and Methodology. Mustafa Ozkaraca: Methodology and Writing-review & editing.

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Correspondence to Ufuk Okkay.

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The experimental protocol was approved by Ataturk University-Ethical Committee (No: E.2100036488).

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Okkay, U., Ferah Okkay, I., Cicek, B. et al. Hepatoprotective and neuroprotective effect of taxifolin on hepatic encephalopathy in rats. Metab Brain Dis 37, 1541–1556 (2022). https://doi.org/10.1007/s11011-022-00952-3

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