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The effects of thymoquinone on memory impairment and inflammation in rats with hepatic encephalopathy induced by thioacetamide

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Abstract

Hepatic encephalopathy (HE) is a prevalent complication of the central nervous system (CNS) that is caused by acute or chronic liver failure. This study was designed to evaluate the effects of thymoquinone (TQ) on thioacetamide (TAA)-induced HE in rats, and determine the consequential behavioral, biochemical, and histological changes. HE was induced in male Wistar rats by intraperitoneal (i.p.) injection of 200 mg/kg TAA once every 48 h for 14 consecutive days. Control groups received the normal saline containing 5 % DMSO. Thymoquinone (5, 10, and 20 mg/kg) was administered for ten consecutive days intraperitoneally (i.p.) after HE induction and it was continued until the end of the tests. Then, the passive avoidance memory, extracellular single unit, BBB permeability, and brain water content were evaluated. Moreover, hippocampal tissues were used for evaluation of oxidative stress index, inflammatory biomarkers, and histological parameters following HE. As result of the treatment, TQ improved passive avoidance memory, increased the average number of simultaneous firing of spikes/bins, improved the integrity of BBB, and decreased brain water content in the animal model of HE. Furthermore, the results indicated that treatment with TQ decreased the levels of inflammatory cytokines (TNF-α and IL-1β) but increased the levels of glutathione (GSH) and anti-inflammatory cytokine (IL-10) of the surviving cells in the hippocampal tissues. This study demonstrates that TQ may have beneficial therapeutic effects on cognitive, oxidative stress, neuroinflammatory, and histological complications of HE in rat.

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Data availability

The data that supports the findings of this study could be accessed through the corresponding author upon reasonable request.

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Acknowledgements

This article was extracted from Miss Somayeh Hajipour’s Ph.D. thesis. This study was financially supported by the Research Affairs Deputy of Ahvaz Jundishapur University of Medical Sciences (grant No. APRC- 9617).

Funding

The authors did not receive any financial support from any organization for the submitted work. The authors have no affiliation with any organization with a direct or indirect financial interest in the subject matter discussed in the manuscript.

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Authors and Affiliations

  1. Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Somayeh Hajipour, Alireza Sarkaki, Mahin Dianat & Yaghoob Farbood

  2. Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Alireza Sarkaki, Mahin Dianat & Yaghoob Farbood

  3. Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Alireza Sarkaki

  4. Department of Immunology, Faculty of Medicine, Cellular & Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Mohammad Rashno

  5. Department of Anatomical Sciences, Cellular & Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Laaya Sadat Khorsandi

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  1. Somayeh Hajipour
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Contributions

All authors have participated in (a) conception and design, or analysis and interpretation of the data; (b) drafting the article or revising it critically for important intellectual content; and (c) approval of the final version.

1. SH analyzed the electrophysiological data and contributed in writing the manuscript.

2. AS designed, guided, and supervised the project and monitored the electrophysiological records.

3. MD was responsible for confirming the TAA-induced HE, analyzed the liver enzyme changes, and revised the article.

4. MR was responsible for the biochemical factors analyses.

5. LKH performed and interpreted the histological examinations of the brains.

6. YF was responsible for monitoring and approving the behavioral tests in different experimental groups.

Corresponding author

Correspondence to Yaghoob Farbood.

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Ethics approval

This article does not contain any studies with human participants performed by any of the authors. The ethics governing the use and conduct of experiments on animals were strictly observed, and all the procedures used in this study were done according to the National Institute of Health (NIH) and were approved by the Local Ethics Committee of Ahvaz Jundishapur University of Medical Sciences (AJUMS) (Ethics code: IR.AJUMS.REC.1396.684).

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Hajipour, S., Sarkaki, A., Dianat, M. et al. The effects of thymoquinone on memory impairment and inflammation in rats with hepatic encephalopathy induced by thioacetamide. Metab Brain Dis 36, 991–1002 (2021). https://doi.org/10.1007/s11011-021-00688-6

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