Effect of L-Arginine Supplementation on Seizure Severity and Comorbid Cognitive Impairment in Pentylenetetrazole-Induced Epilepsy

Abstract

Background: Cognitive impairment is a common comorbidity in epilepsy with no definitive treatment. L-arginine has been shown to improve cognition in experimental animals. Objective: This study investigated the effect of L-arginine on seizure severity and cognition in pentylenetetrazole-induced epilepsy. Materials and Methods: Forty-two male albino rats were administered pentylenetetrazole (PTZ) intraperitoneally at a dose of 35 mg/kg thrice weekly for 6 weeks. Kindled rats were divided into 5 treatment groups: DW; control administered distilled water at 10 mL/kg, LMT; lamotrigine at 62 mg/kg daily, CBZ; carbamazepine at 93 mg/kg twice daily, L-ARG; L-arginine at 100 mg/kg daily, and L-ARG+CBZ; L-arginine at 100 mg/kg daily plus carbamazepine 93 mg/kg twice daily orally. At 4 weeks on treatment, antiseizure effect was tested using sub-convulsive dose of PTZ. At week 5, cognition was assessed using Y-maze and Morris Water-Maze (MWM) tests. Serum samples were obtained for nitro-oxidative stress parameters assay at week 6. Results: There was no significant difference in seizure severity in the L-ARG versus control groups. However, L-ARG+CBZ significantly (p<0.001) increased seizure latency and reduced (p<0.05) Racine stage and seizure duration compared to DW. L-ARG and L-ARG+CBZ also significantly increased (p<0.05) percentage correct alternation and reduced (p<0.01) escape latency versus DW. There were no significant differences in serum nitro-oxidative stress parameters between the groups. Conclusion: L-arginine potentiated the antiepileptic effect of carbamazepine and improved cognition in epileptic rats. L-arginine may be repurposed for managing cognitive dysfunction in epilepsy, but the precise mechanism(s) of action needs to be investigated.