METHANOLIC EXTRACT OF BACOPA MONNIERA REDUCE DEVELOPMENT OF TOLERANCE TO ANTIEPILEPTIC EFFECT OF PHENOBARBITONE IN MICE
Objective: Side effects and development of tolerance to antiepileptic drugs necessitate identifying alterative and improved approaches to treat epilepsy. Bacopa monniera (BM), is a natural product which is used to treat epilepsy. We evaluated effect of co-administration of BM with phenobarbitone (PHB) to prevent development of tolerance to PHB.
Methods: Male Swiss albino mice (25-30 gm-) were divided into six groups. Group 1 and 2 served as controls, which received vehicle and PHB (25 mg/kg, i. p.) respectively. In Group 3 maximal electric shock (MES) was induced two hs following administration of PHB (25 mg/kg, i. p.) at alternate day for 18 d. Hind limb tonic extension (HLTE) occurrence on two consecutive days was set as end point. In Group 4, 5 and 6 MES was induced 2 h following co-administration of PHB (25 mg/kg, i. p.) and BM (250, 500 or 750 mg/kg p. o. respectively). Mice behavior tests were performed at the end of the18thday, following which mice were sacrificed and brain was isolated for estimation of malonoldehyde (MDA) and reduced glutathione (GSH) levels.
Results: 82.5% of mice from group 3 developed tolerance to antiepileptic effects of PHB. Co-administration of BM (250, 500 and 750 mg/kg) lead to development of PHB tolerance in 82.5%, 25% and 20% respectively. This beneficial effect of BM was associated with reduced MDA levels and increased GSH levels in brain, suggesting a role of antioxidant pathways in preventing development of tolerance to antiepileptic effects of PHB.
Conclusion: Co-administration of BM prevented the development of tolerance to antiepileptic effects of PHB.
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