Evaluation of the Antiepileptic Effect of N-acetyl Cysteine in Pentylenetetrazole-Induced Kindling Model in Wistar Rats

Epilepsy is a leading cause of neurological disability worldwide. Despite advances in antiseizure medications, 5% of patients experience seizures after 2 years of treatment, 30% remain treatment-resistant, and 25% discontinue therapy due to adverse effects, highlighting the need for more effective and safer options. N-acetyl cysteine (NAC) has potential antiepileptic properties because of its antioxidant action and glutamate-modulatory effect. The study was designed to evaluate the antiepileptic effect of NAC in a pentylenetetrazole (PTZ)-induced kindling model in Wistar rats. Following approval from the Institutional Animal Ethics Committee, a total of 60 male Wistar rats were used in the study. Of these, 12 rats were used to standardize the PTZ-induced kindling model, and the remaining 48 rats were allocated to six experimental groups (n = 8 per group): normal control, disease control, positive control, and three NAC test-dose groups (200, 300, and 400 mg/kg). PTZ (35 mg/kg) was administered intraperitoneally every 48 hours to induce seizures, and study drugs were administered 30 minutes before each PTZ injection. Seizure latency and severity were recorded, and brain tissue was analyzed for glutathione (GSH) and glutamate levels. Data were analyzed using the Kruskal–Wallis and one-way analysis of variance tests, with p < 0.05 considered significant. NAC (300 mg/kg) and (400 mg/kg) significantly increased seizure latency and decreased seizure severity as compared to the disease control group (p < 0.001), with effects that were comparable to the positive control group (sodium valproate). All test doses of NAC significantly elevated GSH levels (p < 0.001), while intermediate- and high-dose NAC demonstrated significantly greater GSH restoration compared with the positive control group. Further, NAC test doses of 300 and 400 mg/kg significantly reduced glutamate levels (p < 0.05); however, sodium valproate showed comparatively greater glutamate-lowering effects. The results demonstrated that NAC, particularly at intermediate and high doses, exerted antiepileptic effects in the PTZ-induced kindling model in Wistar rats, possibly through modulation of oxidative stress and glutamatergic pathways.