Therapeutic Effects of Oleuropein in Improving Seizure, Oxidative Stress and Cognitive Disorder in Pentylenetetrazole Kindling Model of Epilepsy in Mice.

Abstract

Prolonged epileptic seizures are the cause of neuronal death and brain damage. Lesions in different regions of the brain can lead to memory loss and cognitive disorders. It is therefore essential to seek out new neuroprotective drugs. Our aim was to investigate the therapeutic effects of oleuropein in improving seizure, oxidative stress, and cognitive disorder in pentylenetetrazole (PTZ) kindling model of epilepsy in mice. Mice were randomized to four groups; negative control group intraperitoneally receiving PTZ for 10 days, oleuropein group receiving oleuropein (20 mg/kg) 30 min before PTZ administration, positive control group receiving diazepam 30 min before PTZ administration and flumazenil group receiving flumazenil and then oleuropein 30 min before PTZ administration. Epilepsy severity was investigated after final administration of PTZ. Then hippocampal tissues were removed and stored at -70 °C until measurements of the interleukin-1 (IL-1) and glutamate transporter 1 (GLT-1) gene expression were conducted. Oleuropein treatment caused a significant increase in seizure latency and a significant decrease in total frequencies of head ticks, head and upper limbs seizures, the whole body seizures, frequent spinning and jumping and tonic seizures in PTZ receiving mice. IL-1 expression decreased in oleuropein group and GLT-1 levels did not change significantly in this group. Oleuropein treatment caused significant improvement of passive avoidance memory in PTZ receiving mice in shuttle box. Oleuropein can decrease PTZ-induced seizures and memory disorders due to its antioxidant and anti-inflammatory properties and is thus recommended to be used for production of anti-epileptic drugs.