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114307

Lamotrigine and gabapentin ameliorate neurotoxicity induced by lipopolysaccharide in mice

Article

Last updated: 04 Jan 2025

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Tags

Animal models in cancer therapy
Cellular and molecular targeting
Inflammatory and cancer
Novel Conventional chemotherapy

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.

DOI

10.21608/jcbr.2020.38388.1061

Keywords

Acetylcholine esterase, Alzheimer's disease, Gabapentin, glutamate, lamotrigine, Oxidative Stress

Authors

First Name

Nageh

Last Name

El-Mahdy

MiddleName

-

Affiliation

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt

Email

nageh_mahdy@yahoo.com

City

Tanta

Orcid

-

First Name

Fatma

Last Name

Al-Hosiny

MiddleName

-

Affiliation

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt

Email

fatmaal.hosiny.pf.2019@gmail.com

City

-

Orcid

-

First Name

Sally

Last Name

Abu-Risha

MiddleName

E

Affiliation

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt

Email

sally.abouresha@pharm.tanta.edu.eg

City

Tanta

Orcid

-

Volume

5

Article Issue

1

Related Issue

23533

Issue Date

2021-03-01

Receive Date

2020-08-07

Publish Date

2021-03-01

Page Start

133

Page End

142

Print ISSN

2682-261X

Online ISSN

2682-2628

Article File

JCBR_Volume 5_Issue 1_Pages 133-142.pdf

PDF . 2.6MB

Link

https://jcbr.journals.ekb.eg/article_114307.html

Detail API

https://jcbr.journals.ekb.eg/service?article_code=114307

Order

13

Type

Original Article

Type Code

885

Publication Type

Journal

Publication Title

International Journal of Cancer and Biomedical Research

Publication Link

https://jcbr.journals.ekb.eg/

MainTitle

Lamotrigine and gabapentin ameliorate neurotoxicity induced by lipopolysaccharide in mice

Details

Type

Article

Created At

22 Jan 2023