Montelukast's potential as a neuroprotective agent against acrylamide induced neurotoxicity: In vivo and computational modelling

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology Pub Date : 2025-04-11 DOI:10.1016/j.fct.2025.115448

Abdulaziz Arif A. Alshammari , Minhajul Arfeen , Abdullah Saleh Alkhamiss , Mai B. Alwesmi , Vasudevan Mani

{"title":"Montelukast's potential as a neuroprotective agent against acrylamide induced neurotoxicity: In vivo and computational modelling","authors":"Abdulaziz Arif A. Alshammari , Minhajul Arfeen , Abdullah Saleh Alkhamiss , Mai B. Alwesmi , Vasudevan Mani","doi":"10.1016/j.fct.2025.115448","DOIUrl":null,"url":null,"abstract":"<div><div>Tobacco consumption, a leading cause of over 8 million deaths annually, exposes individuals to acrylamide (ACY), a neurotoxin in cigarette smoke that disrupts neurotransmitter function and induces oxidative stress, contributing to neurodegeneration. This study evaluated neuroprotective potential of montelukast (MTLU), a leukotriene receptor antagonist with anti-inflammatory and antioxidant properties, against ACY-induced neurotoxicity. Cognitive performance was assessed using elevated plus maze, novel object recognition, and Y-maze tests over 14 days. Biomarkers associated with neurodegeneration (BACE1, GSK-3β, AChE), neuroinflammation (COX-2, PGE2, TNF-α, NF-κB), oxidative stress (GSH, MDA, CAT), and apoptosis (Bcl-2, Caspase-3, Bax) were analyzed. Histopathological analyses of brain tissues were conducted to examine structural damage, and computational studies provided additional support for selected in vivo findings. MTLU significantly ameliorated ACY-induced cognitive deficits and reduced levels of GSK-3β, AChE, COX-2, PGE2, TNF-α, NF-κB, MDA, Bax, and Caspase-3 while enhancing antioxidant defenses (GSH) and upregulating Bcl-2. Histopathological analysis confirmed reduced structural brain damage, and molecular docking indicated strong binding potential for MTLU with AChE, COX-2, GSK-3β, BACE-1, and Caspase-3. While these findings suggest a protective role for MTLU in mitigating ACY-induced cognitive impairments, oxidative stress, neuroinflammation, and apoptosis, further research is needed to confirm its therapeutic potential and clinical relevance.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115448"},"PeriodicalIF":3.9000,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Food and Chemical Toxicology","FirstCategoryId":"97","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0278691525002169","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"FOOD SCIENCE & TECHNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Tobacco consumption, a leading cause of over 8 million deaths annually, exposes individuals to acrylamide (ACY), a neurotoxin in cigarette smoke that disrupts neurotransmitter function and induces oxidative stress, contributing to neurodegeneration. This study evaluated neuroprotective potential of montelukast (MTLU), a leukotriene receptor antagonist with anti-inflammatory and antioxidant properties, against ACY-induced neurotoxicity. Cognitive performance was assessed using elevated plus maze, novel object recognition, and Y-maze tests over 14 days. Biomarkers associated with neurodegeneration (BACE1, GSK-3β, AChE), neuroinflammation (COX-2, PGE2, TNF-α, NF-κB), oxidative stress (GSH, MDA, CAT), and apoptosis (Bcl-2, Caspase-3, Bax) were analyzed. Histopathological analyses of brain tissues were conducted to examine structural damage, and computational studies provided additional support for selected in vivo findings. MTLU significantly ameliorated ACY-induced cognitive deficits and reduced levels of GSK-3β, AChE, COX-2, PGE2, TNF-α, NF-κB, MDA, Bax, and Caspase-3 while enhancing antioxidant defenses (GSH) and upregulating Bcl-2. Histopathological analysis confirmed reduced structural brain damage, and molecular docking indicated strong binding potential for MTLU with AChE, COX-2, GSK-3β, BACE-1, and Caspase-3. While these findings suggest a protective role for MTLU in mitigating ACY-induced cognitive impairments, oxidative stress, neuroinflammation, and apoptosis, further research is needed to confirm its therapeutic potential and clinical relevance.

Abstract Image

查看原文本刊更多论文

孟鲁司特作为抗丙烯酰胺诱导的神经毒性的神经保护剂的潜力：体内和计算模型

烟草消费是每年造成800多万人死亡的主要原因，它使人接触到丙烯酰胺（ACY），这是香烟烟雾中的一种神经毒素，会破坏神经递质功能，诱发氧化应激，导致神经退行性变。本研究评估了孟鲁司特（MTLU）的神经保护潜力，孟鲁司特是一种具有抗炎和抗氧化特性的白三烯受体拮抗剂，对acy诱导的神经毒性具有保护作用。在14天的时间里，通过高架+迷宫、新物体识别和y形迷宫测试来评估认知能力。分析与神经退行性变（BACE1、GSK-3β、AChE）、神经炎症（COX-2、PGE2、TNF-α、NF-κB）、氧化应激（GSH、MDA、CAT）和细胞凋亡（Bcl-2、Caspase-3、Bax）相关的生物标志物。对脑组织进行组织病理学分析以检查结构损伤，计算研究为选定的体内研究结果提供了额外的支持。MTLU可显著改善acy诱导的认知缺陷，降低GSK-3β、AChE、COX-2、PGE2、TNF-α、NF-κB、MDA、Bax和Caspase-3水平，同时增强抗氧化防御（GSH）和上调Bcl-2。组织病理学分析证实MTLU减少了结构性脑损伤，分子对接表明MTLU与AChE、COX-2、GSK-3β、BACE-1和Caspase-3有很强的结合潜力。虽然这些发现表明MTLU在减轻acy诱导的认知障碍、氧化应激、神经炎症和细胞凋亡方面具有保护作用，但需要进一步的研究来证实其治疗潜力和临床相关性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Food and Chemical Toxicology 工程技术-毒理学

CiteScore

10.90

自引率

4.70%

发文量

651

审稿时长

31 days

期刊介绍： Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs. The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following: -Adverse physiological/biochemical, or pathological changes induced by specific defined substances -New techniques for assessing potential toxicity, including molecular biology -Mechanisms underlying toxic phenomena -Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability. Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.