Insight into the negative effect and lipid profile alterations in liver of mice exposed to methylimidazolium ionic liquids, a novel "green" solvent.

Abstract

Ionic liquids (ILs) have been recognized as potential environmentally friendly solvents; however, their potential toxicity to living organisms warrants thorough investigation, particularly for novel-generation ILs in mammalian models. In this study, we examined the hepatic effects and disruption of lipid metabolism in mice exposed to 1-heptyl-3-methylimidazolium chloride (C7[MIM]Cl), a novel ILs. After four weeks of oral administration at different dosages (2.38, 5.95, and 11.9mg/kg b.w.), we conducted clinical chemistry analysis and histopathological examination of the liver to assess biochemical and structural changes. The low-dose C7[MIM]Cl group exhibited a significant increase in alanine aminotransferase (ALT) levels, while aspartate aminotransferase (AST) levels were elevated in both low-dose and high-dose groups without statistical significance. Histopathological examination showed inflammatory cell infiltration and red blood cell aggregation in the livers of mice exposed to C7[MIM]Cl, particularly in the high-dose group. Oxidative stress levels showed moderate changes in response to C7[MIM]Cl exposure. Notably, hepatic biochemical parameters revealed a dose-dependent increase in triglycerides (TG) levels with statistically significant differences compared to the control group (P≤0.01). Targeted lipidomic analysis revealed notable alterations in liver lipids of mice exposed to C7[MIM]Cl, with lysophosphatidylethanolamine (18:0), phosphatidylcholines (18:0), and phosphatidylcholines (19:0) identified as critical lipids associated with C7[MIM]Cl exposure. Furthermore, metabolic pathway analyses demonstrated significant disturbances in the glycerophospholipid metabolic pathway. These findings provide valuable insights into the hepatic effects of C7[MIM]Cl exposure and novel perspectives on the disruption of lipid metabolism underlying ILs toxicity.