Abstract
Objective
The study aimed to investigate the ameliorative potential of Agmatine in mitochondrial drug-resistant epilepsy (DRE) owing to its ability to maintain neurochemical homeostasis and antioxidant effect.
Material and Method:
Adult albino mice(n = 42) were subjected to rotenone corneal kindling (2.5 mg/kg i.p.) with daily electric shocks (15 mA, 20V, 6Hz for 3s) via corneal electrode to develop mitochondrial DRE. The pre-treatment validation was carried using five standard ASDs (Pregabalin, Levetiracetam, Carbamazepine, Lamotrigine, and Phenytoin). Thereafter, animals were divided into six groups (excluding naïve): one control, and others received Agmatine (Agm) (5, 10 mg/kg i.p.) and Valproate (Val) (300 mg/kg i.p.) individually and in combination. The post-treatment resistance validation was conducted with same ASDs in same order following treatment phase. Further, the neurochemical (agmatine, arginine, GABA, glutamate, serotonin, and norepinephrine) and biochemical (GSH, Catalase, and TBARS) milieu were assessed in cortex and hippocampus regions of brain.
Results
The inability to reduce seizure severity by standard ASDs after 15-day kindling procedure, confirms the development of drugs resistance. Agmatine effectively eliminated resistance as post-treatment ASDs administration following the treatment phase as revealed by decreased in seizure severity scores. It also showed neurochemical modulatory activity as evidenced by elevated levels of agmatine, arginine, GABA, serotonin, norepinephrine and reduced glutamate levels and antioxidant activity by showing raised levels of GSH, catalase and lowered TBARS level. More Significant outcomes were found with combination of Agm 10 mg/kg and valproate 300 mg/kg
Conclusion
The present study revealed the reversal of drugs resistance in rotenone model of DRE by agmatine through its neurochemical modulatory and anti-oxidant property.