The effects of acute and chronic metformin treatment on penicillin induced epileptiform activity in rats

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. Key words: Antioxidant, Electrocorticography, Epilepsy, Epileptiform Activity, Metformin