Neuroprotective effects of thymoquinone against spinal cord ischemia-reperfusion injury by attenuation of inflammation, oxidative stress, and apoptosis

Emre Cemal Gökce Department of Neurosurgery, Turgut Özal University, Faculty of Medicine;

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Ramazan Kahveci Department of Neurosurgery, Ministry of Health, Çanakkale State Hospital, Çanakkale;

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Aysun Gökce Department of Pathology, Ministry of Health, Diskapi Yildirim Beyazit Education and Research Hospital;

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Berker Cemil Department of Neurosurgery, Turgut Özal University, Faculty of Medicine;

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Nurkan Aksoy Department of Biochemistry, Kirikkale University, Faculty of Medicine, Kirikkale; and

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Mustafa Fevzi Sargon Department of Anatomy, Hacettepe University, Faculty of Medicine;

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Üçler Kısa Department of Biochemistry, Kirikkale University, Faculty of Medicine, Kirikkale; and

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Bülent Erdoğan Department of Neurosurgery, Turgut Özal University, Faculty of Medicine;

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Yahya Güvenç Department of Neurosurgery, Ministry of Health, Ankara Sincan State Hospital; and

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Fatih Alagöz Department of Neurosurgery, Ministry of Health, Ankara Numune Education and Research Hospital, Ankara;

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Ozan Kahveci Department of Emergency Medicine, Faculty of Medicine, Bulent Ecevit University, Zonguldak, Turkey

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OBJECTIVE

Ischemia-reperfusion (I/R) injury of the spinal cord following thoracoabdominal aortic surgery remains the most devastating complication, with a life-changing impact on the patient. Thymoquinone (TQ), the main constituent of the volatile oil from Nigella sativa seeds, is reported to possess strong antioxidant, antiinflammatory, and antiapoptotic properties. This study investigated the effects of TQ administration following I/R injury to the spinal cord.

METHODS

Thirty-two rats were randomly allocated into 4 groups. Group 1 underwent only laparotomy. For Group 2, aortic clip occlusion was introduced to produce I/R injury. Group 3 was given 30 mg/kg of methylprednisolone intraperitoneally immediately after the I/R injury. Group 4 was given 10 mg/kg of TQ intraperitoneally for 7 days before induction of spinal cord I/R injury, and administration was continued until the animal was euthanized. Locomotor function (Basso, Beattie, and Bresnahan scale and inclined plane test) was assessed at 24 hours postischemia. Spinal cord tissue samples were harvested to analyze tissue concentrations of malondialdehyde, nitric oxide, tumor necrosis factor–α, interleukin-1, superoxide dismutase, glutathione-peroxidase, catalase, and caspase-3. In addition, histological and ultrastructural evaluations were performed.

RESULTS

Thymoquinone treatment improved neurological outcome, which was supported by decreased levels of oxidative products (malondialdehyde and nitric oxide) and proinflammatory cytokines (tumor necrosis factor–α and interleukin-1), increased activities of antioxidant enzymes (superoxide dismutase, glutathione-peroxidase, and catalase), as well as reduction of motor neuron apoptosis. Light microscopy and electron microscopy results also showed preservation of tissue structure in the treatment group.

CONCLUSIONS

As shown by functional, biochemical, histological, and ultrastructural analysis, TQ exhibits an important protective effect against I/R injury of the spinal cord.

ABBREVIATIONS

BBB = Basso, Beattie, and Bresnahan; CAT = catalase; ELISA = enzyme-linked immunosorbent assay; GSH-Px = glutathione-peroxidase; IL-1 = interleukin-1; IP = inclined plane; IQR = interquartile range; I/R = ischemia-reperfusion; MDA = malondialdehyde; MP = methylprednisolone; NO = nitric oxide; SOD = superoxide dismutase; TNFα = tumor necrosis factor–α; TQ = thymoquinone.
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