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    The Anti-Convulsant Effects of Carvacrol in Penicillin- and Pentylenetetrazole-Induced Rat Models of Epilepsy
    (Maik Nauka/Interperiodica/Springer, 2024) Eksik, Handan; Ankarali, Seyit; Torun, Ibrahim Ethem; Kilinc, Erkan; Ankarali, Handan
    Epileptic seizures are caused by abnormal neuronal excitation. It is well established that carvacrol, a monoterpenoid phenol, is able to inhibit the voltage-gated sodium channels and L-type Ca2+ channels and enhance activation of GABA(A) receptors. We therefore hypothesize that carvacrol may prevent epileptic seizures by inhibiting neuronal cation influx and facilitating anion influx. Herein, we investigated possible anti-convulsant effects of carvacrol on penicillin-induced epileptiform activity and pentylenetetrazole (PTZ)-induced seizures in rats. 63 male Wistar rats were assigned to the penicillin- and the pentylenetetrazole-induced groups. Both subgroups received three different doses of carvacrol (25, 75, and 150 mg/kg) intraperitoneally. Seizure stage, onset-times of both myoclonic-jerk and generalized tonic-clonic seizures and the duration of generalized tonic-clonic seizure were evaluated using Racine's scale in PTZ group, while spike frequency and the amplitude of epileptiform discharges were evaluated in the penicillin-induced group. The administration of carvacrol significantly extended the onset time of the first myoclonic jerk (150 mg/kg, p = 0.019) and decreased the number of spike-waves (75 mg/kg, p = 0.033). This study showed that carvacrol has the anti-convulsant effect. However, this effect was observed at a low level. The limited the anti-convulsant effect of carvacrol may be due to its insufficient of acute effect related to the transition of carvacrol to the epileptic focus. More studies are needed to evaluate the effect of carvacrol on chronic epilepsy models and its molecular and pharmacokinetic mechanisms.
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    Esculetin Exerts Anti-nociceptive Effects by Suppressing CGRP and c-fos Expression and Mast Cell Activation in an Experimental Migraine Model
    (Wiley, 2023) Gonul, Ayca Nur; Torun, Ibrahim Ethem; Kilinc, Yasemin Baranoglu; Kilinc, Erkan
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    Histopathological effects on kidney of diclofenac potassium and diazepam used in an experimental epilepsy model
    (2023) Saylan, Aslihan; Turel, Canan Akünal; Türel, Idris; Çetinkaya, Ayhan; Torun, Ibrahim Ethem; Çelik, Humeyra
    Aim: To investigate the effects of diazepam, which has anticonvulsant and anxiolytic effects, and diclofenac potassium, which has anti-inflammatory, analgesic and antipyretic effects, on rat kidney tissue, used in an experimental epilepsy model. Methods: 32 Wistar albino rats (2-4 months old, 200-250 gr) were used in the study. The rats were grouped in four as 8 rats in each group: Epilepsy, Epilepsy + Diazepam, Epilepsy + Diclofenac potassium, Epilepsy + Diazepam + Diclofenac potassium. Epileptic seizure model was created with penicillin (500.000 IU) injected intracortically under urethane anesthesia. 30 minutes later, diazepam (0.1 mg/kg) and diclofenac potassium (10 mg/kg) were administered intraperitoneally. At the end of the study, rat kidneys were removed and evaluated histopathologically in terms of inflammation, glomerular shrinkage, tubular dilatation, tubular epithelial thinning, desquame epithelium, brush epithelial loss, vacuolization, hemorrhage and congestion. Results: No difference was found between diazepam and diclofenac potassium in terms of vacuolization, glomerular shrinkage, tubular dilatation and hemorrhage. Inflammation, congestion and tubular epithelial thinning rate were found to be lower inEpilepsy + Diclofenac potassium and Epilepsy + Diazepam + Diclofenac potassium group when compared with Epilepsy + Diazepam group. While brush epithelial loss and desquame epithelial rate was found to be lowest in the epilepsy group, these parameters were not found to show a significant difference between drug groups. Conclusion: It was concluded that combined use of diazepam and diclofenac potassium in their effects on kidney are more useful than their single use.
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    The MT2 Receptor-Mediated Therapeutic Effects of Melatonin in In-Vivo and Ex-Vivo Rat Models of Migraine
    (Wiley, 2023) Kilinc, Erkan; Torun, Ibrahim Ethem; Kilinc, Yasemin Baranoglu; Tore, Fatma
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    Protective effects of long-term probiotic mixture supplementation against pentylenetetrazole-induced seizures, inflammation and oxidative stress in rats
    (Elsevier Science Inc, 2021) Kilinc, Erkan; Ankarali, Seyit; Ayhan, Didem; Ankarali, Handan; Torun, Ibrahim Ethem; Cetinkaya, Ayhan
    Emerging evidence indicates that dysbiosis of gut microbiota plays an important role in epilepsy, although the underlying mechanisms remain unclear due to the complex nature of both microbial composition and pathophysiology of epilepsy. We investigated effects of long-term probiotics supplementation on epileptic seizures, and inflammatory and oxidant/antioxidant biomarkers in a pentylenetetrazole(PTZ)-induced seizure model in rats. Male Wistar weaner-rats were divided into four groups. The first two groups received 1 ml/day saline solution, while the other groups received 0.05 mg/1ml/day vehicle or 109cfu/1ml/day probiotic-mixture, respectively, for 60 days by gavage. Seizure was induced by a single convulsive dose of PTZ. Seizures were evaluated using Racine's scale. Concentrations of pro-inflammatory cytokines in plasma and brain tissue were determined using ELISA, while oxidant/antioxidant biomarkers were measured using an automated-colorimetric method. Probiotics supplementation exhibited anticonvulsant effects against PTZ-induced seizures by retarding onset-times of both myoclonic-jerk and generalized tonic-clonic seizure, and by shortening duration of generalized tonic-clonic seizure. Additionally, it alleviated PTZ-induced increases in levels of pro-inflammatory cytokines IL-1 beta, IL-6, and IL-17A, but not of IFN gamma, in plasma and brain tissue. Moreover, it restored PTZinduced fluctuations in levels of oxidants TOS and disulfide, and of antioxidants native thiol and total thiol. Our findings suggest that long-term probiotics supplementation exhibits protective effects against epileptic seizures, and alleviates (neuro)inflammation and oxidative stress related to pathophysiology of epilepsy. A probiotic-rich diet provided from childhood may provide prophylaxis against epileptic seizures, especially in susceptible individuals, as the neonate diet represents a fundamental extrinsic factor in establishing gut microbiota. (C) 2021 Elsevier Inc. All rights reserved.