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Potential for cardiac toxicity with methylimidazolium ionic liquids

Lookup NU author(s): Dr Tarek Mamdouh AbdelghanyORCiD, Shireen Hedya, Carol De Santis, Dr Jason GillORCiD, Professor Matthew Wright



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


© 2022 The Authors. Methylimidazolium ionic liquids (MILs) are solvent chemicals used in industry. Recent work suggests that MILs are beginning to contaminate the environment and lead to exposure in the general population. In this study, the potential for MILs to cause cardiac toxicity has been examined. The effects of 5 chloride MIL salts possessing increasing alkyl chain lengths (2 C, EMI; 4 C, BMI; 6 C; HMI, 8 C, M8OI; 10 C, DMI) on rat neonatal cardiomyocyte beat rate, beat amplitude and cell survival were initially examined. Increasing alkyl chain length resulted in increasing adverse effects, with effects seen at 10−5 M at all endpoints with M8OI and DMI, the lowest concentration tested. A limited sub-acute toxicity study in rats identified potential cardiotoxic effects with longer chain MILs (HMI, M8OI and DMI) based on clinical chemistry. A 5 month oral/drinking water study with these MILs confirmed cardiotoxicity based on histopathology and clinical chemistry endpoints. Since previous studies in mice did not identify the heart as a target organ, the likely cause of the species difference was investigated. qRT-PCR and Western blotting identified a marked higher expression of p-glycoprotein-3 (also known as ABCB4 or MDR2) and the breast cancer related protein transporter BCRP (also known as ABCG2) in mouse, compared to rat heart. Addition of the BCRP inhibitor Ko143 – but not the p-glycoproteins inhibitor cyclosporin A - increased mouse cardiomyocyte HL-1 cell sensitivity to longer chain MILs to a limited extent. MILs therefore have a potential for cardiotoxicity in rats. Mice may be less sensitive to cardiotoxicity from MILs due in part, to increased excretion via higher levels of cardiac BCRP expression and/or function. MILs alone, therefore may represent a hazard in man in the future, particularly if use levels increase. The impact that MILs exposure has on sensitivity to cardiotoxic drugs, heart disease and other chronic diseases is unknown.

Publication metadata

Author(s): Abdelghany TM, Hedya SA, De Santis C, Abd El-Rahman SS, Gill JH, Abdelkader NF, Wright MC

Publication type: Article

Publication status: Published

Journal: Ecotoxicology and Environmental Safety

Year: 2023

Volume: 249

Print publication date: 01/01/2023

Online publication date: 19/12/2022

Acceptance date: 13/12/2022

Date deposited: 04/01/2023

ISSN (print): 0147-6513

ISSN (electronic): 1090-2414

Publisher: Academic Press


DOI: 10.1016/j.ecoenv.2022.114439


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Funder referenceFunder name
Newton-Mosharafa Fund