Inhibition of brain oxidative stress and inducible nitric oxide synthase expression by thymoquinone attenuates the development of morphine tolerance and dependence in mice

Ankaralı

et al. 2016

NSJ

Objective:To investigate the effects of thymoquinone (TQ) in a penicillin-induced epilepsy model in rats.Methods:This experimental study included 56 adult male Wistar rats. Experiments were performed in the Research Laboratory of the Department of Physiology, Medical School, Duzce University, Duzce, Turkey, between October 2013 and December 2014. Animals were divided into the following 7 groups: sham, control, only thymoquinone, vehicle (Dimethylsulfoxide), and doses of 10, 50, and 100 mg/kg of TQ. After rats were anesthetized, the left part of the skull was removed. A pair of silver/silver chloride electrodes was placed on the somatomotor area, and electrocorticographic recording was started. After 5 minutes basal activity was recorded, and TQ was applied intraperitoneally. At the thirtieth minute after TQ, epileptiform activity was induced by intracortical penicillin. The first spike latency, spike frequency, and the amplitude of epileptiform activity were analyzed statistically.Results:The different doses of TQ significantly increased the latency time to onset of first spike wave, and decreased the frequency, and amplitude of epileptiform activity in the first 20 minutes compared with the control group.Conclusion:Thymoquinone shows potential as an antiepileptic drug resulting from its effects of prolonged latency time, and reduced spike wave frequency and amplitude of epileptiform activity.

Section: Discussionmentioning

confidence: 73%

Effects of thymoquinone, the major constituent of Nigella sativa seeds, on penicillin-induced epileptiform activity in rats

Ankaralı

et al. 2016

NSJ

“…Abdel-Zaher et al demonstrated that morphine tolerance and dependence, brain oxidative stress, and increased inducible NO synthase expression were attenuated by co-administration with TQ in mice. However, morphine-induced progressive increase in the brain glutamate level was not inhibited by this compound [39]. TQ and N. sativa seeds oil protected against lipid peroxidation level induced by global cerebral ischemia-reperfusion injury in the hippocampus of rats [40].…”

Section: Discussionmentioning

confidence: 96%

Effects of Intraperitoneal Thymoquinone on Chronic Neuropathic Pain in Rats

2014

In this study, we evaluated the protective effects of thymoquinone, the major constituent of Nigella sativa seeds on the neuropathic pain of rats with chronic constrictive injury of the sciatic nerve. Rats received repeated administration of thymoquinone (1.25, 2.5, and 5 mg/kg, i. p.) once a day for 14 days, beginning immediately after the nerve injury. Mechanical allodynia, cold allodynia, and thermal hyperalgesia were assessed with the von Frey filament, acetone drop, or radiant heat stimulus, respectively. Recent evidence points towards a role of oxidative stress, spinal glia activation, and cell death in the pathogenesis of neuropathic pain. Ionized calcium-binding adapter molecule 1 (a marker of microglia), glial fibrillary acidic protein (a marker of astroglia), Bcl2-associated X protein (a proapoptotic protein), and B-cell lymphoma protein 2 (an antiapoptotic protein) were measured using Western blot on days 3, 7, and 14 post chronic constrictive injury. The changes in the protein levels of malondialdehyde and glutathione, biomarkers of oxidative stress, were assessed by spectrophotometric assay on day 14 post chronic constrictive injury. Repeated treatment with thymoquinone (2.5 and 5 mg/kg) significantly alleviated behavioral signs of neuropathic pain. In the lumbar spinal cord of neuropathic rats, ionized calcium-binding adapter molecule 1 and Bcl2-associated X protein increased on day 3 post chronic constrictive injury, whereas B-cell lymphoma protein 2 did not significantly change. After repeated thymoquinone administration, the elevated Bcl2-associated X protein and ionized calcium-binding adapter molecule reduced on day 3, while the level of B-cell lymphoma protein 2 was even stimulated. Ionized calcium-binding adapter molecule and Bcl2-associated X protein/B-cell lymphoma protein 2 ratio declined by days 7 and 14; consequently, there were no significant differences among groups. No or little change was observed in the glial fibrillary acidic protein content during the study. Chronic constrictive injury produced a significant increase in the levels of malondialdehyde and decrease in the contents of glutathione on day 14. Thymoquinone treatment (2.5 and 5 mg/kg) restored the levels of malondialdehyde. High dose of thymoquinone (5 mg/kg) also reversed the decreased glutathione in the injured animals. Our results indicate that, microglia, apoptotic factors, and oxidative stress rather than astroglia contribute to the pathogenesis of chronic constrictive injury, and thymoquinone plays an anti-nociceptive role possibly by antioxidant effects and inhibition of microglia activity.

“…A number of studies have demonstrated TQ's antioxidant 28,37 and antiinflammatory effects in the treatment of inflammatory diseases, cancer, 51 atherosclerosis, 36,41 and diabetes. 7 Various mechanisms of action have been suggested for TQ, such as inhibition of the cyclooxygenase and 5-lipoxidase pathways; suppression of the proinflammatory cytokines IL-1b and TNFa; 8 as well as augmentation of the antioxidant defense through preserving the activity of various antioxidant enzymes, such as CAT, GSH-Px, 1 and SOD. 49 Other properties ascribed to TQ include its inhibition of nonenzymatic lipid peroxidation in liposomes and its action as a potent free radical and superoxide radical scavenger.…”

Section: Discussionmentioning

confidence: 99%

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

Gökçe

Kahveci

Gökçe³

et al. 2016

SPI

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.