Sıçanlarda penisilinle oluşturulan epileptiform aktivite üzerine akut ve kronik metformin tedavisinin etkileri
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Tarih
2021
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Yayıncı
Düzce Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Sıçanlarda Penisilinle Oluşturulan Epileptiform Aktivite Üzerine Akut ve Kronik Metformin Tedavisinin Etkileri Epilepsi dünya çapında her yaştan yaklaşık 50 milyon insanı etkileyen, tekrarlayan nöbetlerle karakterize nörolojik bir beyin hastalığıdır. Tedavisinde antiepileptik ilaçlar, özel diyetler, vagal sinir stimülasyonu ve cerrahi yöntemler kullanılmasına rağmen hastaların yaklaşık % 30'unda epilepsi hala kontrol edilememektedir. Kullanılan ilaçların birçoğunun ciddi yan etkileri vardır. Metformin, yeni tip 2 diabetes mellitus tanısı konmuş hastalarda temel tedavi olarak kullanılan biguanid grubu oral antidiyabetiktir. Ayrıca metforminin, oksidatif stres, nöroinflamasyon, apoptozis ve nöronal kayıp da dahil olmak üzere moleküler ve hücresel değişiklikleri modifiye etme potansiyeli olduğu bilinmektedir. Bu çalışmanın amacı penisilin ile oluşturulan epileptiform aktivite üzerine metforminin kronik ve akut etkilerini belirlemek için nöbet başlangıç latensi, diken dalga sayısı, diken dalga genliğinin elektrofizyolojik olarak incelenmesidir. Ayrıca antioksidan özelliğini belirlemek amacıyla SOD (Süperoksit Dismutaz), GPx (Glutatyon Peroksidaz) ve CAT (Katalaz) enzim değerlerine bakılmıştır. Bu çalışmada 84 adet yetişkin erkek Wistar albino sıçan kullanıldı. Sıçanlar akut ve kronik gruplar olmak üzere iki büyük gruba ayrıldıktan sonra her bir grup kontrol, sham, penisilin, metformin 100 mg/kg intraperitoneal (i.p), 200 mg/kg (i.p) ve sadece metformin 200 mg/kg (i.p) dozlarda farklı alt gruba ayrıldı. Kronik gruplara maddeler 21 gün, akut gruplara ise sadece epileptiform aktivite öncesi uygulandı. Sıçanların 1.25 g/kg'lık üretan anestezisi altında somatomotor alana yerleştirilen elektrotlar aracılığıyla elektrofizyolojik kayıtları alındı. Akut gruplara beş dakikalık bazal aktivite kaydından sonra metformin enjekte edildi. Metformin uygulamasının 30. dakikasında penisilin (500 IU) intrakortikal olarak uygulandı. Penisilin sonrası 120 dakika daha ECoG kaydı alındı. Kronik gruplarda beş dakikalık bazal aktivite kaydı sonrasında penisilin intrakortikal uygulanarak 120 dakika daha ECoG kaydı alındı. Kan serum örneklerinde süperoksit dismutaz, katalaz ve glutatyon peroksidaz seviyeleri belirlendi. Kayıtlardan elde edilen ECoG verileri yazılım programı labchart ile analiz edildi. Kontrol, Sham ve sadece metformin gruplarında hiçbir epileptiform aktivite görülmemiştir. Metforminin 100 mg/kg, 200 mg/kg'lık dozları hem akut hem de kronik gruplarda penisilin grubu ile kıyaslandığında, ilk epileptiform aktivite başlangıç latensi uzamış, diken dalga sayısı ve diken dalga genliği anlamlı olarak azalmıştır. Akut ve Kronik metformin gruplarında SOD, CAT ve GPx seviyeleri penisilin grubuna göre anlamlı bulunmuştur. Sonuç olarak bu çalışma metforminin, epileptik nöbetleri hafifletebileceği ve antioksidan enzimleri artırabileceği ve gelecekte epilepsi tedavisinde kullanılabileceğini göstermektedir.
The Effects of Acute and Chronic Metformin Treatment on Penicillin Induced Epileptiform Activity in Rats Epilepsy is a neurological brain disease characterized by recurrent seizures and it affects globally around 50 million people of all ages. Although the antiepileptic drugs, special diets, vagal nerve stimulation and surgical methods are used in its treatment, epilepsy still cannot be controlled in nearly 30% of the patients. Majority of the used drugs causes serious side effects. Metformin is a biguanide group oral antidiabetic addressed as the main therapy in patients with newly diagnosed type 2 diabetes mellitus. It is also known that metformin has the potential to modify molecular and cellular changes, including oxidative stress, neuroinflammation, apoptosis, and neuronal loss. The aim of this study is to analyse the seizure onset latency, spike wave frequency, spike wave amplitude by using electrophysiological techniques to determine the chronic and acute effects of metformin on the epileptiform activity induced by penicillin. During the research, in addition to the main aim, SOD (Superoxide Dismutase), GPx (Glutathione Peroxidase) and CAT (Catalase) enzyme values were also examined to detect the antioxidant properties. Eighty-four adult male Wistar albino rats were used in this study. The rats were divided into two large groups as acute and chronic groups, and later on each group was divided into different subgroups as control, sham, penicillin, metformin 100 mg/kg intraperitoneal (i.p), 200 mg/kg (i.p) and metformin alone 200 mg/kg (i.p). The substances were assigned to the chronic groups for 21 days, and the acute groups received them just before the epileptiform activity. The electrophysiological records of the rats were taken by means of electrodes placed in the somatomotor area under 1.25 g / kg urethane anesthesia. Metformin was injected to the acute groups after five minutes of basal activity recording. Penicillin (500 IU) was applied intracortically at the 30th minute of metformin injection. The ECoG recording was taken for another 120 minutes after penicillin. After five minutes of basal activity recording in chronic groups, penicillin was applied intracortically and ECoG recording was taken for another 120 minutes. The superoxide dismutase, catalase and glutathione peroxidase levels were measured in blood serum samples. The ECoG data obtained from the records were analysed with the software program labcard. No epileptiform activity was observed in the control, Sham, and metformin alone groups. When 100 mg/kg, 200 mg/kg doses of metformin in both acute and chronic groups were compared with the penicillin group, the initial epileptiform activity latency extended, the number of spike waves and spike wave amplitude significantly decreased. SOD, CAT and GPx levels were found to be significant in the acute and chronic metformin groups in comparison with the penicillin group. In conclusion, this study shows that the metformin can alleviate epileptic seizures and increase antioxidant enzymes and can be used in the treatment of epilepsy in the future.
The Effects of Acute and Chronic Metformin Treatment on Penicillin Induced Epileptiform Activity in Rats Epilepsy is a neurological brain disease characterized by recurrent seizures and it affects globally around 50 million people of all ages. Although the antiepileptic drugs, special diets, vagal nerve stimulation and surgical methods are used in its treatment, epilepsy still cannot be controlled in nearly 30% of the patients. Majority of the used drugs causes serious side effects. Metformin is a biguanide group oral antidiabetic addressed as the main therapy in patients with newly diagnosed type 2 diabetes mellitus. It is also known that metformin has the potential to modify molecular and cellular changes, including oxidative stress, neuroinflammation, apoptosis, and neuronal loss. The aim of this study is to analyse the seizure onset latency, spike wave frequency, spike wave amplitude by using electrophysiological techniques to determine the chronic and acute effects of metformin on the epileptiform activity induced by penicillin. During the research, in addition to the main aim, SOD (Superoxide Dismutase), GPx (Glutathione Peroxidase) and CAT (Catalase) enzyme values were also examined to detect the antioxidant properties. Eighty-four adult male Wistar albino rats were used in this study. The rats were divided into two large groups as acute and chronic groups, and later on each group was divided into different subgroups as control, sham, penicillin, metformin 100 mg/kg intraperitoneal (i.p), 200 mg/kg (i.p) and metformin alone 200 mg/kg (i.p). The substances were assigned to the chronic groups for 21 days, and the acute groups received them just before the epileptiform activity. The electrophysiological records of the rats were taken by means of electrodes placed in the somatomotor area under 1.25 g / kg urethane anesthesia. Metformin was injected to the acute groups after five minutes of basal activity recording. Penicillin (500 IU) was applied intracortically at the 30th minute of metformin injection. The ECoG recording was taken for another 120 minutes after penicillin. After five minutes of basal activity recording in chronic groups, penicillin was applied intracortically and ECoG recording was taken for another 120 minutes. The superoxide dismutase, catalase and glutathione peroxidase levels were measured in blood serum samples. The ECoG data obtained from the records were analysed with the software program labcard. No epileptiform activity was observed in the control, Sham, and metformin alone groups. When 100 mg/kg, 200 mg/kg doses of metformin in both acute and chronic groups were compared with the penicillin group, the initial epileptiform activity latency extended, the number of spike waves and spike wave amplitude significantly decreased. SOD, CAT and GPx levels were found to be significant in the acute and chronic metformin groups in comparison with the penicillin group. In conclusion, this study shows that the metformin can alleviate epileptic seizures and increase antioxidant enzymes and can be used in the treatment of epilepsy in the future.
Açıklama
Anahtar Kelimeler
Fizyoloji, Physiology, Antioksidan, Elektrokortikografi,Epilepsi, Epileptiform Aktivite, Metformin, Antioxidant, Electrocorticography, Epilepsy, Epileptiform Activity, Metformin
