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Role of Oxidative Stress, MAPKinase and Apoptosis Pathways in the Protective Effects of Thymoquinone Against Acrylamide-Induced Central Nervous System Toxicity in Rat

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Abstract

The present study evaluated biochemical endpoints characterizing acrylamide (ACR) neurotoxicity in the cortex of rats, following the possible neuroprotective activity of thymoquinone (TQ), an active constituent of Nigella sativa. ACR (50 mg/kg, intraperitoneal [i.p.]) concurrently with TQ (2.5, 5 and 10 mg/kg, i.p.) for 11 days were administered to rats. As positive control, vitamin E was used. After 11 days of injections, narrow beam test (NBT) was performed. The levels of reduced glutathione (GSH) and malondialdehyde (MDA) were measured and Western blotting was done for mitogen-activated protein kinases (MAPKinases) and apoptosis pathways proteins in the rats’ cortex. Additionally, Evans blue assay was done to evaluate the integrity of blood brain barrier (BBB). Administration of ACR significantly induced gait abnormalities. A significant decrease and increase in the levels of GSH and MDA was observed in the cortex of ACR-treated rats, respectively. The elevation in the levels of caspases 3 and 9, glial fibrillary acidic protein (GFAP) content, and Bax/Bcl-2, P-P38/P38 and P-JNK/JNK ratios accompanied by reduction in myelin basic protein (MBP) content and P-ERK/ERK ratio were noticed in the ACR group. TQ (5 mg/kg) improved gait abnormalities, and restored these changes. ACR affected the integrity of BBB while TQ was able to maintain the integrity of this barrier. TQ reversed the alterations in the protein contents of MAP kinase and apoptosis signaling pathways as well as MBP and GFAP contents, induced by ACR. It protected against ACR-mediated neurotoxicity, partly through its antioxidant and antiapoptotic properties.

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Acknowledgements

Authors are grateful to the Vice Chancellor of Research, Mashhad University of Medical Sciences, Mashhad, Iran for financial support. The data reported in this article are part of a Ph.D. thesis.

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Authors and Affiliations

  1. Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Jamshid Tabeshpour, Soghra Mehri & Hossein Hosseinzadeh

  2. Faculty of Pharmacy, Damghan Branch, Islamic Azad University, Damghan, Iran

    Jamshid Tabeshpour

  3. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Soghra Mehri, Khalil Abnous & Hossein Hosseinzadeh

  4. Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Khalil Abnous

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Tabeshpour, J., Mehri, S., Abnous, K. et al. Role of Oxidative Stress, MAPKinase and Apoptosis Pathways in the Protective Effects of Thymoquinone Against Acrylamide-Induced Central Nervous System Toxicity in Rat. Neurochem Res 45, 254–267 (2020). https://doi.org/10.1007/s11064-019-02908-z

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