Investigation of Antiepileptic, Antiinflammatory and Antioxidative Potential of Betahistine in Pentylentetrazole Induced Acute Seizure Model
Abstract
Epilepsi kronik bir nörolojik bozukluktur. Epileptik nöbetler, eksitasyon ve inhibisyon arasındaki hassas dengenin bozulmasından kaynaklanmaktadır. Bu çalışmanın amacı betahistinin, ratlarda pentilentetrazol (PTZ) ile indüklenen akut nöbet modelinde nöbet gelişimi, oksidatif stres ve inflamasyon süreçlerine etkilerinin tespit edilmesidir. Wistar albino erkek rat rastgele 4 ayrı gruba ayrıldı (n=28); 1) Kontrol, 2) Pentilentetrazol+Serum Fizyolojik (PTZ+SF), 3) Pentilentetrazol+Betahistin-1 (PTZ+BH-1) ve 4)Pentilentetrazol+Betahistin-10 (PTZ+BH-10). Ratlara, 8 gün boyunca betahistin (1 ve 10 mg/kg) veya serum fizyolojik (SF) enjekte edildi. 8. gün betahistin veya SF enjeksiyonundan yarım saat sonra deney gruplarındaki ratlara PTZ (65 mg/kg, i.p.) enjekte edildi. İlk miyoklonik jerk (IMJ), jeneralize tonik klonik nöbet (JTKN) ve jeneralize tonik ekstensiyon (JTE) latansı kaydedildi. Beyin dokusunda malondialdehit (MDA), süperoksit dismutaz (SOD), katalaz (CAT), tümör nekroz faktör-α (TNF-α), interlökin-6 (IL-6) ve interlökin-1β (IL-1β) parametreleri ELISA ile araştırıldı. IMJ ve JTKN latansı açısından anlamlı fark bulunmadı. PTZ+SF grubunun SOD değeri kontrol grubuna göre anlamlı derecede azaldı (p<0.05). PTZ+BH-1 grubuna ait SOD ve MDA değerleri kontrol grubuna göre anlamlı derecede düşük bulundu (p<0.05). CAT değeri PTZ+BH-1 grubunda kontrol ve PTZ+BH-10 gruplarına göre anlamlı derecede düşük bulundu (p<0.05). SOD değeri PTZ+BH-10 grubunda PTZ+BH-1 grubuna göre anlamlı derecede yüksek bulundu (p<0.05). MDA değeri PTZ+BH-10 grubunda kontrol grubuna göre anlamlı derecede düşük bulundu (p<0.05). PTZ+SF grubu IL-1β değeri diğer gruplara göre anlamlı derecede yüksek bulundu (p<0.05). PTZ+BH-1 grubuna ait TNF-α, IL-6 ve IL-1β değerleri diğer gruplara göre anlamlı derecede düşük bulundu (p<0.05). Sonuç olarak, veriler düşük dozda (1 mg/kg) betahistin'in antioksidan kapasiteyi arttırdığını ve proinflamatuar sitokin düzeylerini baskıladığını gösterdi. Bununla birlikte, betahistin uygulamasının sıçanlarda PTZ (65 mg/kg) ile indüklenen akut nöbetler üzerinde anti/prokonvulsan önleyici etkisi olmamıştır.
Epilepsy is a chronic neurological disorder. Epileptic seizures result from the disruption of the delicate balance between excitation and inhibition. The aim of the present study was to determine the effects of betahistine on seizure development, oxidative stress and inflammation processes in pentylenetetrazole (PTZ) induced acute seizure model in rats. Wistar albino male rats were randomly divided into 4 groups (n=28): 1) Control, 2) Pentylenetetrazole+ Physiological saline (PTZ+PS), 3) Pentylenetetrazole+Betahistin-1 (PTZ+BH-1) and 4) Pentylenetetrazole+Betahistine-10 (PTZ+BH-10). The rats were injected with betahistine (1 and 10 mg/kg) or physiological saline (PS) for 8 days. On the 8th day, half an hour after betahistine or SF injection, the rats in the experimental groups were injected with PTZ (65 mg/kg, i.p.). First myoclonic jerk (IMJ), generalized tonic clonic seizure (JTKN), and generalized tonic extension (JTE) latencies were recorded. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) parameters were investigated in the brain tissue by ELISA. There was no significant difference in terms of IMJ and JTKN latencies. The SOD level of the PTZ+PS group was significantly decreased compared to the control group (p<0.05). SOD and MDA levels of the PTZ+BH-1 group were significantly lower than the control group (p<0.05). The CAT level was found to be significantly lower in the PTZ+BH-1 group compared to the control and PTZ+BH-10 groups (p<0.05). SOD level was found to be significantly higher in the PTZ+BH-10 group than in the PTZ+BH-1 group (p<0.05). MDA level was found to be significantly lower in the PTZ+BH-10 group compared to the control group (p<0.05). The IL-1β level of the PTZ+PS group was found to be significantly higher than the other groups (p<0.05). TNF-α, IL-6 and IL-1β levels of the PTZ+BH-1 group were found to be significantly lower than the other groups (p<0.05). In conclusion, the data suggested that betahistine at low dose (1 mg/kg) increased antioxidant capacity and suppressed proinflammatory cytokine levels. However, betahistin administration had no anti/pro-convulsant effect on PTZ (65 mg/kg) induced acute seizures in rats.
Epilepsy is a chronic neurological disorder. Epileptic seizures result from the disruption of the delicate balance between excitation and inhibition. The aim of the present study was to determine the effects of betahistine on seizure development, oxidative stress and inflammation processes in pentylenetetrazole (PTZ) induced acute seizure model in rats. Wistar albino male rats were randomly divided into 4 groups (n=28): 1) Control, 2) Pentylenetetrazole+ Physiological saline (PTZ+PS), 3) Pentylenetetrazole+Betahistin-1 (PTZ+BH-1) and 4) Pentylenetetrazole+Betahistine-10 (PTZ+BH-10). The rats were injected with betahistine (1 and 10 mg/kg) or physiological saline (PS) for 8 days. On the 8th day, half an hour after betahistine or SF injection, the rats in the experimental groups were injected with PTZ (65 mg/kg, i.p.). First myoclonic jerk (IMJ), generalized tonic clonic seizure (JTKN), and generalized tonic extension (JTE) latencies were recorded. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) parameters were investigated in the brain tissue by ELISA. There was no significant difference in terms of IMJ and JTKN latencies. The SOD level of the PTZ+PS group was significantly decreased compared to the control group (p<0.05). SOD and MDA levels of the PTZ+BH-1 group were significantly lower than the control group (p<0.05). The CAT level was found to be significantly lower in the PTZ+BH-1 group compared to the control and PTZ+BH-10 groups (p<0.05). SOD level was found to be significantly higher in the PTZ+BH-10 group than in the PTZ+BH-1 group (p<0.05). MDA level was found to be significantly lower in the PTZ+BH-10 group compared to the control group (p<0.05). The IL-1β level of the PTZ+PS group was found to be significantly higher than the other groups (p<0.05). TNF-α, IL-6 and IL-1β levels of the PTZ+BH-1 group were found to be significantly lower than the other groups (p<0.05). In conclusion, the data suggested that betahistine at low dose (1 mg/kg) increased antioxidant capacity and suppressed proinflammatory cytokine levels. However, betahistin administration had no anti/pro-convulsant effect on PTZ (65 mg/kg) induced acute seizures in rats.
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Fizyoloji, Antioksidanlar, Betahistin, Epilepsi, Nöbetler, Pentilentetrazol, Polimeraz zincirleme reaksiyonu, Physiology, Antioxidants, Betahistine, Epilepsy, Seizures, Pentylenetetrazole, Polymerase chain reaction
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