Anticonvulsant Activity of Naringenin in Wistar Rats: Reduction in Inflammation Biomarkers

Introduction: Spontaneous and recurrent epileptic seizures cause neuroinflammation, whereas the chronic administration of antiepileptic drugs may lead to hepatotoxicity and nephrotoxicity. Investigating natural compounds such as naringenin, which exhibits antioxidant, anti-inflammatory, and neuroprotective properties, could mitigate these toxic effects. However, whether naringenin delays seizure onset through anti-inflammatory mechanisms remains unclear. Objective: We evaluated the anticonvulsant effect of subchronic naringenin administration and its impact on inflammatory biomarkers in rats. Methods: Thirty-two male Wistar rats were divided into four groups (n = 8 each): vehicle (10% DMSO), naringenin (50 mg/kg), naringenin (100 mg/kg), and diazepam (4 mg/kg). Treatments were administered once daily for ten days through the intraperitoneal route. On day 11, status epilepticus (SE) was induced via the lithium-pilocarpine model. One hour after SE onset, cardiac blood was collected, and the serum was analyzed via ELISA to quantify the following inflammatory markers: superoxide dismutase (SOD), C-reactive protein (CRP), carbonyl protein, and nitrite/nitrate. Results: We found that 100 mg/kg naringenin increased the latency to SE and the first generalized seizure and shortened the duration of generalized seizures. Fifty percent of the rats in the 100 mg/kg naringenin group did not develop SE. The group treated with 100 mg/kg naringenin demonstrated reduced levels of CRP, protein carbonyls, and nitrates; conversely, the inhibition of SOD activity increased. Conclusions: Naringenin exerted anticonvulsant activity associated with a reduction in oxidative stress and inflammatory plasma biomarkers, suggesting its potential utility in the future development of alternative treatments to reduce epilepsy symptoms.