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Thymoquinone modifies CD4+:CD8+ ratio without affecting tumor necrosis factor-α and interleukin-1β levels in Wallerian degeneration crush injury rat model

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Abstract

Wallerian degeneration following nerve injury not only suppresses CD4+ T-cell responses but also promotes pro-inflammatory immunological responses through TNF-α and IL-1β. Recent research suggests that thymoquinone might enhance nerve recovery by exerting anti-inflammatory effects on both the innate and adaptive immune systems. This study aims to evaluate the effect of thymoquinone on neuroinflammation in a sciatic nerve crush injury, as represented by TNF-α, IL-1β, and the CD4+:CD8+ ratio. In this study, 126 crush injury Wistar rats were divided into three main groups: placebo, thymoquinone 100 mg/kg, and thymoquinone 250 mg/kg administered daily. Rats were euthanized at six distinct time points: 12, 18, and 24 hours, as well as on day-5, day-6, and day-7. TNF-α and IL-1β levels were assessed using the Enzyme-Linked Immunosorbent Assay (ELISA). The CD4+:CD8+ ratio in peripheral blood was determined via flow cytometry. No significant TNF-α differences was found between treatment and placebo groups. However, on day 6, IL-1β was significantly lower in the TQ 250mg/kg group than in the placebo (p=0.008). A similar but non-significant trend existed on days 6 and 7. On day 5, both TQ groups showed a higher, statistically significant CD4+:CD8+ ratio compared to placebo (p=0.007), a trend that continued to day 7 but not statistically significant. Daily TQ administration did not consistently reduce TNF-α and IL-1ß levels. However, both doses elevated the CD4+:CD8+ ratio during the early stages of Wallerian degeneration, suggesting a potential benefit of TQ on nerve regeneration.

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The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request

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Acknowledgment

The authors would like to acknowledge the staff at the Institute of Tropical Disease, Department of Clinical Pathology and Department of Biochemistry, Faculty of Medicine, Airlangga University, for their technical assistance during this study. This research was additionally guided by the late Professor Mohammad Hasan Machfoed, MD of the Department of Neurology, Faculty of Medicine, Airlangga University in Surabaya, Indonesia.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Faculty of Medicine, University of Surabaya, Surabaya, Jalan Raya Kalirungkut, Indonesia

    Valentinus Besin

  2. Department of Neurosurgery, Faculty of Medicine, Airlangga University, Surabaya, Indonesia

    Abdul Hafid Bajamal

  3. Department of Clinical Pathology, Faculty of Medicine, Airlangga University, Surabaya, Indonesia

    Jusak Nugraha & Paulus Budiono Notopuro

  4. Faculty of Medicine, Airlangga University, Surabaya, Indonesia

    Naesilla Naesilla

  5. Faculty of Medicine Universitas Brawijaya, Malang, Indonesia

    Farizky Martriano Humardani

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  1. Valentinus Besin
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Valentinus Besin and Abdul Hafid Bajamal. The first draft of the manuscript was written by Valentinus Besin and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Valentinus Besin.

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The authors have no relevant financial or non-financial interests to disclose.

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This study was published with the informed consent of all authors

Ethical approval

The study underwent a rigorous review from the Health Research Ethics Committee of the Faculty of Medicine, Airlangga University, Surabaya approved the protocol for this study (4/EC/KEPK/FKUA/2021).

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Besin, V., Bajamal, A.H., Nugraha, J. et al. Thymoquinone modifies CD4+:CD8+ ratio without affecting tumor necrosis factor-α and interleukin-1β levels in Wallerian degeneration crush injury rat model. Neurosci Behav Physi 54, 1–9 (2024). https://doi.org/10.1007/s11055-023-01523-4

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