The Antiepileptogenic Effect of Metformin and Possible Interaction with Neuroinflammation in the Pentylenetetrazole-Kindling Model in Rats

Although the exact origins of epilepsy are unclear, it is suggested that cellular damage, oxidative stress, and neuroinflammation all play a role in the development of epilepsy. Though Metformin was reported to have anti-seizure properties in previous research, more investigations have been required to understand the activity of metformin on the inflammatory markers in epilepsy. The aim of our investigation was to study the antiepileptogenic effect of metformin and its possible interaction with neuroinflammation in the pentylenetetrazole-kindling model in rats. In this investigation, 24 male Wistar albino rats were employed. Four groups of animals were formed (control, pentylenetetrazole, positive control (valproic acid + PTZ), and metformin (metformin + PTZ)). The rats were injected with PTZ (35 mg/kg) 30 min after receiving the medicine or saline once every other day for 12 times, and their behaviors were examined. After completing the epileptic model process, ELISA methods were used to measure inflammatory markers in the cortex and hippocampus (TNF-& alpha;, IL-1 & beta;, NF-kB, COX-1, COX-2, iNOS, and NO). Metformin suppressed seizure stages and decreased TNF-& alpha;, NF-kB, COX-1, COX-2, iNOS, and NO levels in the hippocampus and cerebral cortex. IL-1 & beta; level, on the other hand, is reduced only in the hippocampus. Metformin has antiepileptogenic effect and it might be related its interaction with neuroinflammation.