Effects of Valproate and Deferoxamine on Epileptiform Activity, Oxidative Stress, and Nitric Oxide in a Penicillin-Induced Epilepsy Model

Abstract

Simple Summary Epilepsy is a common neurological disorder in which abnormal electrical activity in the brain causes recurrent seizures. Increasing evidence suggests that oxidative damage and excessive production of nitric oxide, a signaling molecule that can become harmful in large amounts, contribute to brain injury during seizures. This study investigated whether combining the widely used anti-seizure medicine valproate with deferoxamine, a drug that removes excess iron from the body, alters markers of oxidative and nitrosative stress in the brain, in addition to its effects on seizure-related electrical activity. Using an experimental model of epilepsy in rats, we found that both treatments reduced seizure-related electrical activity. Although the combination did not suppress seizures more effectively than valproate alone, it was associated with lower nitrite/nitrate surrogate markers of nitric oxide metabolism and higher hippocampal antioxidant status, while its effects on other oxidative stress markers were mixed. These findings indicate that combining these two agents produces measurable, marker-specific biochemical changes in this acute experimental model. However, the combination did not provide additional suppression of epileptiform activity compared with valproate alone, and whether the biochemical changes have functional significance remains to be determined in future studies.