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Lookup NU author(s): Dr Tarek Abdelghany, Alexandra Charlton, Dr Catherine ArdenORCiD, Emeritus Professor Matthew Wright
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 by the authors. M8OI is a cytotoxic methylimidazolium ionic liquid solvent through its binding to the ubiquinone binding site on complex I of the mitochondrial electron transport chain. Given the overlap in terms of toxic mechanism of action with the pesticide rotenone, the potential neurotoxic effects of M8OI were examined. In vitro, cytotoxicity and mitochondrial function were assessed in SH-SY5Y cells by measuring MTT reduction and oxygen consumption/extracellular acidification using a Seahorse analyser. SH-SY5Y cells were sensitised to M8OI toxicity by replacing medium glucose with galactose. Glucose protected the cells from M8OI toxicity, whereas galactose showed no clear dose–response protection. M8OI induced a dose-dependent reduction in oxygen consumption rate with a compensatory increase in extracellular acidification rate, consistent with inhibition of mitochondrial oxidative phosphorylation and a shift toward glycolysis. In vivo, rats were orally exposed via drinking water for 20 weeks and assessed using behavioural tests. In addition, the concentrations of M8OI and its metabolites were quantified by LC–MS in rat brain and other tissues. In rats, M8OI concentrations were ~30-fold higher in kidney than brain, and brain levels were at least 100-fold lower than the concentrations that affected SH-SY5Y cell viability in vitro. However, based on open field tests, M8OI exposure suppressed motor activity without any anxious behaviours. The cytotoxicity of M8OI in SH-SY5Y neuroblastoma cells was associated with metabolic mitochondrial dysfunction. However, the neurobehavioural changes observed in orally exposed rats occurred at significantly lower brain concentrations than would be predicted to lead to neural cell death. Nevertheless, direct comparisons between acute in vitro exposures and chronic in vivo outcomes should be interpreted cautiously.
Author(s): Abdelghany TM, Budastour AA, Kamel AS, Ibrahim SM, Charlton A, Wilkinson S, Arden C, Abdelkader NF, Wright MC
Publication type: Article
Publication status: Published
Journal: Journal of Xenobiotics
Year: 2026
Volume: 16
Issue: 3
Online publication date: 17/06/2026
Acceptance date: 10/06/2026
Date deposited: 15/07/2026
ISSN (print): 2039-4705
ISSN (electronic): 2039-4713
Publisher: MDPI
URL: https://doi.org/10.3390/jox16030113
DOI: 10.3390/jox16030113
Data Access Statement: The original contributions presented in this study are included in the article/Supplementary Materials. Further inquiries can be directed to the corresponding author.
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