Given the limited therapeutic options for patients with epilepsy – particularly those with drug-resistant forms –non-pharmacological interventions such as physical exercise and specialised dietary approaches have gained increasing attention. This study aimed to investigate the combined effects of endurance training and a ketogenic diet enrichedwith medium-chain triglycerides (MCT) on the activity of glutamate oxaloacetate transaminase (GOT) and the levels of glutamate and γ-aminobutyric acid (GABA) in the CA1 region of the hippocampus in maleWistar rats with pentylenetetrazole (PTZ)-induced epilepsy. Thirty-five adult maleWistar rats (200–250 g) were randomly assigned to five groups: control, epilepsy, epilepsy + exercise, epilepsy + MCT, and epilepsy + exercise + MCT. Epilepsy was induced by subcutaneous injections of PTZ (35 mg/kg) every 48 h for two weeks. After induction of epilepsy, the exercise groups underwent an eight-week endurance training protocol on a treadmill (five days per week) with progressively increased intensity, whileMCT groups received aMCT-enriched ketogenic diet. At the end of the intervention period, serum GOT levels and hippocampal glutamate and GABA levels were measured using ELISA. Results indicated that PTZ-induced epilepsy significantly decreasedGABA (P < 0.01) and elevated glutamate levels (P < 0.001) in the hippocampus. In contrast, endurance exercise combined with the MCT diet significantly increased GOT (P < 0.01) and GABA levels (P < 0.05), while reducing glutamate concentrations (P < 0.01). Endurance training in combination with a ketogenic MCT diet may enhance neuroprotection by restoring the excitatory–inhibitory balance within the hippocampus, thereby offering a promising adjunctive approach for the management of epilepsy.
