Anticonvulsant potential of rosuvastatin in combination with carbamazepine and valproate in animal models of epilepsy

Background: Epilepsy impacts millions of people, with many not responding to existing treatments. Some evidence links neuroinflammatory processes to epilepsy. Statins exhibit anti-inflammatory and neuroprotective properties, potentially offering antiepileptic effects.

Aim: To evaluate the anticonvulsant effects of rosuvastatin in animal models of epilepsy.

Methods: Ninety-six albino mice were divided into 16 groups. In the maximal electroshock seizure (MES) model, eight groups received intraperitoneal vehicle, carbamazepine, rosuvastatin, or a combination. Outcomes measured included seizure protection [tonic hind limb extension (THLE)], duration of THLE, seizure duration, and mortality. In the pentylenetetrazol (PTZ) model, eight groups were pretreated with vehicle, valproate, rosuvastatin, or a combination, with outcomes measured as seizure latency, seizure duration, and mortality.

Results: In the MES model, rosuvastatin exhibited protection against THLE in a small percentage of mice. Rosuvastatin shortens the duration of THLE in a dose-dependent manner. However, none of these were statistically significant compared to the control group. The combination of rosuvastatin 10 mg/kg with carbamazepine 4 mg/kg resulted in a significant reduction in seizure duration compared to the control group, better than carbamazepine alone at 4 mg/kg and 6 mg/kg. In the PTZ model, rosuvastatin alone showed no significant effects on latency, duration of seizure, or mortality. However, rosuvastatin 10 mg/kg combined with valproate 100 mg/kg significantly delayed the onset of seizures, seizure duration and mortality percentage, better than valproate alone at 100 mg/kg.

Conclusion: Rosuvastatin enhanced the anticonvulsant effects of carbamazepine and valproate. Further studies are required to explore the antiepileptic potential of rosuvastatin at various doses, durations, dosage forms, routes and models.

Anticonvulsant; Antiepileptic; Maximal electroshock seizure; Pentylenetetrazol; Rosuvastatin; Statins.