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Emerging risk from "environmentally-friendly" solvents: Interaction of methylimidazolium ionic liquids with the mitochondrial electron transport chain is a key initiation event in their mammalian toxicity

Lookup NU author(s): Dr Tarek Mamdouh Abdelghany, Dr Alistair Leitch, Dr Ibrahim Ibrahim, Dr Satomi Miwa, Colin Wilson, Professor Matthew Wright

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Recent studies have identified the 8C alkyl chain methylimidazolium ionic liquid 1-octyl-3-methylimidazolium in the environment and its potential to trigger the auto-immune liver disease primary biliary cholangitis. The toxicity of a range of methylimidazolium ionic liquids were therefore examined. Oxygen consumption was rapidly inhibited, with potency increasing with alkyl chain length. This preceded caspase 3/7 induction and DNA fragmentation. Time- and dose-dependent loss of dye reduction capacities reflected these effects, with a >700 fold difference in potency between 2C and 10C alkyl chain liquids. None of the ionic liquids directly inhibited mitochondrial complexes I-IV or complex V (F0F1-ATPase). However, dithionite reduction and ESR spectroscopy studies indicate a one electron reduction of oxygen in the presence of a methylimidazolium ionic liquid, suggesting methylimidazolium ionic liquids function as mitochondrial electron acceptors. However, only longer chain ionic liquids form a non-aqueous phase or micelle under aqueous physiological conditions and lead to increases in reactive oxygen species in intact cells. These data therefore suggest that the longer chain methylimidazolium liquids are toxic in sensitive liver progenitor cells because they both readily integrate within the inner mitochondrial membrane and accept electrons from the electron chain, leading to oxidative stress.


Publication metadata

Author(s): Abdelghany TM, Leitch AC, Nevjestic I, Ibrahim I, Miwa S, Wilson C, Heutz S, Wright MC

Publication type: Article

Publication status: Published

Journal: Food and Chemical Toxicology

Year: 2020

Volume: 145

Pages: 111593

Print publication date: 01/11/2020

Online publication date: 07/08/2020

Acceptance date: 08/07/2020

Date deposited: 19/08/2020

ISSN (print): 0278-6915

Publisher: Elsevier

URL: https://doi.org/10.1016/j.fct.2020.111593

DOI: 10.1016/j.fct.2020.111593

PubMed id: 32777338


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