Lamotrigine and gabapentin ameliorate neurotoxicity induced by lipopolysaccharide in mice | ||||
| Egyptian Journal of Cancer and Biomedical Research | ||||
| Article 13, Volume 5, Issue 1, March 2021, Page 133-142 PDF (2.45 MB) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/jcbr.2020.38388.1061 | ||||
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| Authors | ||||
Nageh El-Mahdy; Fatma Al-Hosiny  ; Sally E Abu-Risha
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| Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt | ||||
| Abstract | ||||
| Background: Alzheimer’s disease (AD), the most common cause for dementia, is an irreversible progressive neurodegenerative disorder. Aim: To investigate the potential protective role of Lamotrigine (LTG) and Gabapentin (GBP) either alone and in combination in Lipopolysaccride-induced Alzheimer's disease (AD) in mice. Materials and Methods: Mice were divided into 5 groups: Normal control group, Lipopolysaccride (LPS) group (animals were injected by single I.P. dose of LPS in a dose of 0.8 mg/kg), LTG group (animals were injected by single I.P. dose of LPS 0.8 mg/kg and received oral LTG 30 mg/kg/day), GBP group (animals were injected by single I.P. dose of LPS 0.8 mg/kg and received oral GBP 200 mg/kg/day) and LTG+GBP group (animals were injected by single I.P. dose of LPS 0.8 mg/kg and received both oral LTG 30 mg/kg/day and GBP 200 mg/kg/day), therapy started 2-h after LPS injection for 7 successive days. Novel object recognition and Y-maze tests were conducted. Brain homogenate used for the estimation of superoxide dismutase (SOD), acetylcholine esterase (AchE) activity, glutamate, reduced glutathione (GSH) and malonyialdehyde (MDA) contents. Results: LPS significantly induced neurobehavioral disturbances compared to normal control with significantly higher MDA, AchE and glutamate contents, with a reduction in SOD and GSH levels. Treatment with either LTG or GBP significantly ameliorated the effects of LPS injection on neurobehavioral tests, oxidative milieu with a significant reduction in AchE activity and glutamate content in favor of LTG. Combined therapy significantly improved both neurobehavioral testing and the estimated biochemical markers. Conclusion: GBP and/or LTG therapy improved neurobehavioral testing in LPS- induced AD in mice by restoring oxidant/antioxidant milieu with a concomitant reduction in AchE activity and glutamate content. Furthermore; the combination of both drugs resulted in significant improvement than either one of them alone that merits further clinical investigation. | ||||
| Keywords | ||||
| Acetylcholine esterase; Alzheimer's disease; Gabapentin; Glutamate; Lamotrigine; Oxidative stress | ||||
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