Effect of acute and chronic ellagic acid administration on penicillin induced epileptiform activity in rats

There are about 65 million people with epilepsy on earth, and a large part of the patients are resistant to antiepileptic drugs ever discovered. In addition, the side effect profile of these drugs is very wide. Ellagic acid (EA) is a flavonoid which presents in some of fruits and plant including pomegranate, nuts and apples. Aim of this study was to investigate effects of ellagic acid, which has been shown analgesic, antidepressant, antioxidant and anticancer effects, on experimental penicillin-induced epilepsy model electrophysiologically as well as oxidative stress. In this study 94 adult male Wistar rats were used. After the rats were divided two large groups as acute and chronic, each group were separated into different subgroups as sham, control (penicillin), only EA and 10, 50 and 100 mg / kg doses as EA. All of the substances were administered intraperitoneally except penicillin. When applying substances for 21 days to the chronic study group, in the acute study groups these substances were administered only before the epileptiform activity. Rats were anesthetized with 1.25 g/kg dose urethane intraperitoneally, the left part of the bone on cortex had been removed, and electrodes were placed onto somatomotor area. After recording five-minutes basal activity in acute groups, EA was applied. After the 30 minutes administration of EA, intracortical penicillin (500 IU) was injected. ECoG was recorded for 120 minutes more after the penicillin administration. In the chronic groups penicillin were applied intracortically and ECoG recording was taken 120 minutes more after the recording of 5 minutes basal activity. Also superoxide dismutaz, catalase and glutatyon peroxidase in blood serum were determined by ELISA. Electrocorticographic data which obtained from recordings were analyzed by the software program. Meanwhile the latency time to onset of first spike-wave, spike-wave frequency and amplitude of epileptiform activity were analyzed as data. There was no epileptiform activity in sham and only EA (non-induced with penicillin) groups. When both acute and chronic groups of 10 mg/kg, 50 mg/kg and 100 mg/kg of EA doses were compared to the control group, significantly increased the latency time to onset of first spike wave and decreased the frequency and amplitude except some time periods were found. SOD, CAT and GPx levels of chronic groups were found lower than control group. Consequently, the results of the present study show that administration of ellagic acid has antiepileptic effect in penicillin induced model of epilepsy in rats and it may be a potential antiepileptogenic drug in future.