Document Details
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Document Type |
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Thesis |
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Document Title |
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EFFECT OF THYMOQUINONE ON ANTIEPILEPTIC EFFECT OF CARBAMAZEPINE IN ANIMAL MODEL تاثير الثيموكينون على فاعلية الكربامازبين لمعالجة الصرع فى النماذج التجريبيه |
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Subject |
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Faculty of medicine |
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Document Language |
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Arabic |
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Abstract |
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Background: Epilepsy is one of the well-known neurological disorders, affecting 65 million patients worldwide. It is not a particular disease, but rather a type of disorders characterized by the presence of paroxysmal and recurrent seizure activity.
Objectives: This experiment studied the efficacy of thymoquinone (TQ), alone and in combination to carbamazepine, in preventing epilepsy seizures and explored its effect on the brain neuro-excitatory activity.
Methods: Forty-eight Swiss albino (SWR) male mice were randomized into 6 groups, each receiving a specific 30-days treatment regimen including one daily intraperitoneal injection of Tween 80 (negative control), 5mg/kg TQ (TQ-5), 10mg/kg TQ (TQ-10), 25mg/kg carbamazepine (CBZ.), 5mg/kg TQ + 25mg carbamazepine (TQ-5+CBZ.), and 10mg/kg TQ + 25mg carbamazepine (TQ-10+CBZ.). On the 31st day, all animals underwent chemically-induced seizure using pentylenetetrazol (PTZ). Subsequently, each animal was put in an open-top 40*40*40cm black opaque box for a 30-minute continuous video recording to analyze post PTZ behavior, along with calculation of the time to seizure and measurement of the severity level using RACINE score. Finally, animals were sacrificed and high-performance liquid chromatography (HPLC) was used to measure glutamate levels in cerebral cortex, cerebellum, pons, medulla, and hippocampus, as an indicator for TQ effect on the brain neuro-excitatory activity.
Results: The administration of TQ alone prevented the occurrence of extremely severe seizures (RACINE 5; incidence from 5/8 to 0/8) in TQ-5 group and shifted the RACINE range from 4.5-5 to 3.5-4 in TQ-10, compared to negative control, respectively. Thus, by defining severe seizure as RACINE score>4, the number needed to treat (NNT) was calculated as 1.3 for TQ 5mg and 1 for 10mg. By combination with carbamazepine, TQ further reduced the severity of seizures in a dose-dependent and synergistic fashion. All previous results were statistically significant. In brain tissue, glutamate concentrations decreased gradually from negative control to TQ-10 in all four studied brain regions including hippocampus (mean [SD] from 3.44 [1.53] to 0.61 [0.57] nmol/mg), cerebellum (from 18.71 [8.31] to1.48 [0.94] nmol/mg), pons and medulla (from 26.94 [7.61] to 2.25 [2.01] nmol/mg), and cortex (from 9.70 [6.66] to 1.99 [1.83] nmol/mg), and the differences were statistically significant (p<0.001). In combination with carbamazepine, TQ further reduced glutamate concentration in a dose-dependent manner in all brain regions. Remarkably, the most significant dose-dependent effect was observed in the hippocampus, where the introduction of progressive dose of TQ draw a downward stair-step of glutamate concentration, and where a peak concertation corresponding to severe seizure was observed and further explored.
Conclusion: Thymoquinone showed great efficacy in reducing seizure severity in a dose-dependent fashion, both alone and with carbamazepine synergistically. These effects were associated with a reduction of glutamate availability and distribution in the brain tissue, especially in hippocampus, where it showed perfect correlation with seizure severity. |
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Supervisor |
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Dr.Lateef M Khan |
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Thesis Type |
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Master Thesis |
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Publishing Year |
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1442 AH
2020 AD |
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Co-Supervisor |
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Dr.Ahmad S Ali |
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Added Date |
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Friday, December 4, 2020 |
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Researchers
| طلال سعود الحارثي | ALHARTI, TALAL SAUD | Researcher | Master | |
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