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Lookup NU author(s): Shireen Hedya, Dr Alex Charlton, Dr Alistair Leitch, Fahad Aljehani, Professor Matt Wright, Dr Tarek Mamdouh AbdelghanyORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
The methylimidazolium ionic liquid M8OI was recently found to be present in both the environment and man. In this study, M8OI disposition and toxicity were examined in an established rat progenitor-hepatocyte model. The progenitor B-13 cell was approx. 13 fold more sensitive to the toxic effects of M8OI than the hepatocyte B-13/H cell. However, this difference in sensitivity was not associated with a difference in metabolic capacities. M8OI toxicity was significantly decreased in a dose-dependent manner by co-addition of the OCT1 (SLC22A1) inhibitor clonidine, but not by OCT2 or OCT3 inhibitors in B-13 cells. M8OI toxicity was also dose-dependently increased by the co-addition of p-glycoprotein-1 (ABCB1B, multi drug resistant protein 1 (MDR1)) substrates/inhibitors. Excretion of B-13-loaded fluorophore Hoechst 33342 was also inhibited by the p-glycoproteins substrate cyclosporin A and by M8OI in a dose-dependent manner. Comparing levels of OCT and p-glycoprotein transcripts and proteins in B-13 and B-13/H cells suggest that the lower sensitivity to M8OI in B-13/H cells is predominantly associated with their higher expression of p-glycoprotein-1. These data together therefore suggest that a determinant in M8OI toxicity in rats is the expression and activity of the p-glycoprotein transporter-1.
Author(s): Hedya S, Charlton A, Leitch AC, Aljehani FA, Pinker B, Wright MC, Abdelghany TM
Publication type: Article
Publication status: Published
Journal: Toxicology in Vitro
Year: 2023
Volume: 88
Print publication date: 01/04/2023
Online publication date: 02/01/2023
Acceptance date: 30/12/2022
Date deposited: 06/01/2023
ISSN (print): 0887-2333
ISSN (electronic): 1879-3177
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/j.tiv.2022.105550
DOI: 10.1016/j.tiv.2022.105550
ePrints DOI: 10.57711/znc6-7947
PubMed id: 36603777
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