alexa Protective Effect of Alpha Lipoic Acid against Phenytoi

Journal of Molecular Biomarkers & Diagnosis
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Research Article

Protective Effect of Alpha Lipoic Acid against Phenytoin Induced Behavioral Abnormalities in Rats

Saraswathy GR1*, Maheswari E2and Santhrani T3

1Department of Pharmacology, M.S. Ramaiah University of Applied Sciences, Karnataka, India

2Department of Pharmacy Practice, M.S. Ramaiah University of Applied Sciences, Karnataka, India

3Department of Pharmacology, Institute of Pharmaceutical Technology, Sri Padmavathi Mahila Visvavidyalayam, Andhra Pradesh, India

*Corresponding Author:
Dr. Saraswathy G.R.
Department of Pharmacology
M.S. Ramaiah University of Applied Sciences
Bangalore, Karnataka, India
Tel: 08123230400
Fax: 080-23607488
E-mail: [email protected]

Received Date: July 08, 2015 Accepted Date: July 28, 2015 Published Date: July 31, 2015

Citation:Saraswathy GR, Maheswari E, Santhrani T (2015) Protective Effect of Alpha Lipoic Acid against Phenytoin Induced Behavioral Abnormalities in Rats. J Mol Biomark Diagn 5: 241. doi:10.4172/2155-9929.1000241

Copyright: ©2015 Saraswathy GR, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited



Background: Long term administration of antiepileptic drug phenytoin is reported to cause behavioral abnormalities mediated via oxidative stress. The effect of an antioxidant alpha lipoic acid (ALA) against phenytoin induced behavioral abnormalities was investigated.

Methods: The study was carried out in albino wistar rats. The rats were divided into five groups of six animals each. Group 1 received 0.2% carboxy methyl cellulose (CMC, p.o), group 2 received 20 mg/kg phenytoin (p.o), groups 3,4 and 5 received 50, 100 and 200 mg/kg (p.o) of ALA in 0.2% CMC, respectively 1 h prior to phenytoin for 45 days. Motor coordination, exploratory behavior, memory and spontaneous motor activity were evaluated by Rota rod, Hole board, Elevated plus maze and Actophotometer respectively. On day 45, regional brain lipid peroxidation and acetylcholinesterase (ACh E) activity along with brain histopathological investigation were performed after euthanasia. In addition, pharmacokinetic and pharmacodynamic drug interactions between phenytoin and ALA were also studied.

Results: Long term administration of phenytoin showed behavioral abnormalities, increased regional brain malondialdehyde (MDA) and ACh E activity. The histopathological investigation showed congested and damaged cells in brain regions. ALA substantially reversed phenytoin induced behavioral abnormalities, oxidative stress and alleviated the histopathological abnormalities. There were no significant differences in the serum levels of phenytoin and the degree of protection offered by phenytoin in ALA supplemented groups revealing that there were no pharmacokinetic and pharmacodynamic interactions between phenytoin and ALA.

Conclusion: This study reports the effectiveness of ALA against phenytoin induced behavioral abnormalities and oxidative stress in rats without altering the bioavailability of phenytoin and its therapeutic effect.

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