Metformin ameliorates pentylenetetrazol-induced seizures in mice by modulating peroxisome proliferator-activated receptor gamma, nuclear factor-kappa B, matrix metalloproteinase 2, and caspase-3.

Owing to less efficiency of currently available antiepileptic medications, research is continuing toward the most effective solution. It was observed that the antidiabetic drug metformin (MET) is getting more attention in the modern world due to its good anti-inflammatory and neuroprotective characteristics, and this is the main purpose of this investigation for assessing the antiepileptic impact of MET. In this study, we sought to assess MET's antiepileptic effectiveness in a model of mice by examining its effects on the duration, frequency, and intensity of seizures. Furthermore, we aimed to figure out the neurological mechanisms behind MET's antiepileptic effects. Six groups of 48 mice were allocated. The first group was administered normal saline (vehicle group), while in the second group, to induce seizure, administered pentylenetetrazol (PTZ; 45 mg/kg). Valproic acid (300 mg/kg) was given to the third group as the positive group. The remaining groups were injected with prophylactic doses of MET at 200, 250, and 300 mg/kg for 7 days. After 30 min of the last dose, Groups 3, 4, 5, and 6 were induced by PTZ. The results showed that MET exerted antiepileptic and neuroprotective effects across behavioral, biochemical, and mortality parameters. The mortality rate, the length of generalized tonic-clonic seizures, the frequency of seizures, and the seizure scores (P < 0.001) were all substantially reduced by the MET. Additionally, MET raised levels of peroxisome proliferator-activated receptor gamma, nuclear factor-kappa B, and matrix metalloproteinase 2 (P < 0.001) while lowering blood levels of caspase-3 (P < 0.001). Findings revealed MET's antiepileptic role, lowering both seizure activity and mortality in the target mouse.