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Allyl isothiocyanate attenuates oxidative stress and inflammation by modulating Nrf2/HO-1 and NF-κB pathways in traumatic brain injury in mice

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Abstract

Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in young adults and children in the industrialized countries; however, there are presently no FDA approved therapies. TBI results in oxidative stress due to the overproduction of reactive oxygen species and overwhelming of the endogenous antioxidant mechanisms. Recently, it has been reported that antioxidants including phytochemicals have a protective role against oxidative damage and inflammation after TBI. To analyze the effects of a naturally occurring antioxidant molecule, allyl isothiocyanate (AITC), on the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa B (NF-κB) signaling pathways in TBI, a cryogenic injury model was induced in mice. Here, we showed that AITC administered immediately after the injury significantly decreased infarct volume and blood–brain barrier (BBB) permeability. Protein levels of proinflammatory cytokines interleukin-1β (IL1β) and interleukin-6 (IL6), glial fibrillary acidic protein (GFAP) and NF-κB were decreased, while Nrf2, growth-associated protein 43 (GAP43) and neural cell adhesion molecule levels were increased with AITC when compared with vehicle control. Our results demonstrated that the antioxidant molecule AITC, when applied immediately after TBI, provided beneficial effects on inflammatory processes while improving infarct volume and BBB permeability. Increased levels of plasticity markers, as well as an antioxidant gene regulator, Nrf2, by AITC, suggest that future studies are warranted to assess the protective activities of dietary or medicinal AITC in clinical studies.

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Abbreviations

AITC:

Allyl isothiocyanate

BBB:

Blood–brain barrier

GAP43:

Growth-associated protein 43

GFAP:

Glial fibrillary acidic protein

ICAM-1:

Intercellular adhesion molecule-1

IL1β:

Interleukin-1β

IL6:

Interleukin-6

NCAM:

Neural cell adhesion molecule

NF-κB:

Nuclear factor kappa B

Nrf2:

Nuclear factor erythroid 2-related factor 2

ROS:

Reactive oxygen species

TBI:

Traumatic brain injury

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Acknowledgements

This study was supported by OmniActive Health Technologies Ltd. NJ, USA. This work was also supported in part by The Turkish Academy of Sciences (TUBA) (KS, EK).

Funding

This study was supported by OmniActive Health Technologies Inc. (NJ, USA). This work was also supported in part by the Turkish Academy of Sciences.

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Authors and Affiliations

  1. Department of Medical Biology, International School of Medicine, Istanbul Medipol University, Istanbul, Turkey

    Berrak Caglayan

  2. Department of Physiology, Istanbul Medipol University, Istanbul, Turkey

    Ertugrul Kilic, Arman Dalay & Serdar Altunay

  3. Regenerative and Restorative Medical Research Center, Istanbul Medipol University, Istanbul, Turkey

    Berrak Caglayan, Ertugrul Kilic, Arman Dalay, Serdar Altunay, Mehmet Yalcin Gunal & Burak Yulug

  4. Division of Biology, Faculty of Science, Firat University, Elazig, Turkey

    Mehmet Tuzcu & Fusun Erten

  5. Animal Nutrition Department, School of Veterinary Medicine, Firat University, Elazig, Turkey

    Cemal Orhan & Kazim Sahin

  6. Department of Neurology, School of Medicine, Istanbul Medipol University, Istanbul, Turkey

    Mehmet Yalcin Gunal & Burak Yulug

  7. Research and Development, OmniActive Health Technologies Inc., Morristown, NJ, USA

    Vijaya Juturu

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  1. Berrak Caglayan
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Correspondence to Kazim Sahin.

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Caglayan, B., Kilic, E., Dalay, A. et al. Allyl isothiocyanate attenuates oxidative stress and inflammation by modulating Nrf2/HO-1 and NF-κB pathways in traumatic brain injury in mice. Mol Biol Rep 46, 241–250 (2019). https://doi.org/10.1007/s11033-018-4465-4

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