Effect of L-Arginine Supplementation on Seizure Severity and Comorbid Cognitive Impairment in Pentylenetetrazole-Induced Epilepsy
), A. Arikawe(2), I. O. Ishola(3), O. Oghene(4), M Abass(5), A. J. Akindele(6), O. Awodele(7), O. O. Adeyemi(8),
(1) Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria.
(2) Department of Physiology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria.
(3) Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria.
(4) Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria.
(5) Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria.
(6) Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria.
(7) Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria.
(8) Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria.
Corresponding Author
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.
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.
Keywords
Epilepsy, Cognition, Pentylenetetrazole, Memory, L-Arginine
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