Renal injury and hepatic effects from the methylimidazolium ionic liquid M8OI in mouse

• Published in: Ecotoxicology and environmental safety 2020-10, Vol.202, p.110902, Article 110902
• Main Authors: Leitch, Alistair C., Abdelghany, Tarek M., Charlton, Alex, Grigalyte, Justina, Oakley, Fiona, Borthwick, Lee A., Reed, Lee, Knox, Amber, Reilly, William J., Agius, Loranne, Blain, Peter G., Wright, Matthew C.
• Format: Article
• Language: English
• Subjects: Animals; C8mim; Fibrosis; Glycogen; Hazardous Substances - toxicity; Ionic Liquids - toxicity; Ions - pharmacology; Kidney; Kidney - drug effects; kim1; Liver; Liver - drug effects; Male; Mice; Mice, Inbred C57BL; Toxicity Tests
• ISSN: 0147-6513; 1090-2414; 1090-2414
• DOI: 10.1016/j.ecoenv.2020.110902

The ionic liquid 1-octyl-3-methylimidazolium (M8OI) has been found in the environment and identified as a hazard for triggering the liver disease primary biliary cholangitis (PBC). Given limited toxicity data for M8OI and other structurally-related ionic liquids, target organs for M8OI toxicity were examined. Adult male C57Bl6 mice were acutely exposed to 0–10 mg/kg body weight M8OI via 2 intraperitoneal injections (time zero and 18 h) and effects examined at 24 h. At termination, tissue histopathology, serum and urinary endpoints were examined. No overt pathological changes were observed in the heart and brain. In contrast, focal and mild to multifocal and moderate degeneration with a general trend for an increase in severity with increased dose was observed in the kidney. These changes were accompanied by a dose-dependent increased expression of Kim1 in kidney tissue, marked elevations in urinary Kim1 protein and a dose-dependent increase in serum creatinine. Hepatic changes were limited to a significant dose-dependent loss of hepatic glycogen and a mild but significant increase in portal tract inflammatory recruitment and/or fibroblastic proliferation accompanied by a focal fibrotic change. Cultured mouse tissue slices reflected these in vivo effects in that dose-dependent injury was observed in kidney slices but not in the liver. Kidney slices accumulated higher levels of M8OI than liver slices (e.g. at 10 μM, greater than 4 fold) and liver slices where markedly more active in the metabolism of M8OI. These data indicate that the kidney is a target organ for the toxic effects of M8OI accompanied by mild cholangiopathic changes in the liver after intraperitoneal administration. •The ionic liquid M8OI [C8mim] has been found in the environment.•Mice were exposed acutely over 24 h to M8OI via i.p. injection.•The kidney was the target organ for toxicity, heart and brain appeared normal.•Hepatic changes were limited to glycogen depletion and mild portal tract changes.•Kidney tissue slices accumulated higher levels of M8OI than liver tissue slices.