Exploring the neuroprotective potential of aprepitant against nicotine-induced molecular, histological, and behavioral sequels

Chronic nicotine exposure causes molecular and behavioral impairments. APRE, a selective NK1R antagonist, has neuroprotective potential. This study investigated whether APRE could protect against nicotine-induced neurotoxicity and mood- and motor-related behavioral changes in adult male Wistar rats.

Forty-eight male Wistar rats were randomly assigned to six groups (n = 8) and treated intraperitoneally once daily for three weeks: group 1 received normal saline (0.5 mL/rat), group 2 received nicotine (10 mg/kg), groups 3–5 received nicotine (10 mg/kg) plus APRE (20, 40, or 80 mg/kg), and group 6 received APRE alone (80 mg/kg). Mood- and motor-related behaviors were assessed using OFT, EPM, and FST. In the hippocampus, mitochondrial function, oxidative stress, inflammation, apoptosis-related JNK/Bcl-2/Bax signaling, Beclin-1, and qualitative and quantitative histopathological changes in the DG and CA1 regions were investigated.

APRE significantly attenuated nicotine-induced mood and motor disturbances. It also increased SOD, GPx, GR activity, TAC, ATP, MMP, GSH, and unphosphorylated Bcl-2, while reducing ROS, MDA, H2O2, GSSG, TNF-α, IL-1β, both forms of JNK, Bax, Beclin-1, and phosphorylated Bcl-2. In nicotine-exposed rats, APRE also significantly improved qualitative and quantitative histopathological changes in the DG and CA1 regions of the rat’s hippocampus.

APRE mitigated multiple untoward effects of nicotine exposure, including behavioral disturbances, neuroinflammation, oxidative stress, cell death, and histopathological damage in the rat’s hippocampus. Ethylene Glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic Acid 5,5’,6,6’-Tetrachloro-1,1’,3,3’ tetraethylbenzimidazolyl-carbocyanine iodide Nicotinamide adenine dinucleotide phosphate (reduced form) We are grateful for the support of Islamic Azad University, Tehran Medical Branch. The student thesis was conducted in the Islamic Azad University of Tehran Medical Branch.

This project has no funding declaration. Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, TeMS.C., Islamic Azad University, Tehran, Iran Active Pharmaceutical Ingredients Research Center (APIRC), TeMS.C., Islamic Azad University, Tehran, Iran Pediatric Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran Shahedeh Maraashi, Mahdieh Gholami & Majid Motaghinejad Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA Center for Environmental Occupational Risk Analysis and Management, College of Public Health, University of South Florida, Tampa, FL, USA Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material.

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