New insight into the negative impact of imidazolium-based ionic liquid [Cmim]Cl on Hela cells: From membrane damage to biochemical alterations.

As an alternative to volatile organic solvents, ionic liquids (ILs) are known as "green solvents", and widely used in industrial applications. However, due to their high solubility and stability, ILs have tendency to persist in the water environment, thus having potential negative impacts on the aquatic ecosystem. For assessing the environmental risks of ILs, a fundamental understanding of the toxic effects and mechanisms of ILs is needed. Here we evaluated the cytotoxicity of 1-methyl-3-decylimidazolium chloride ([Cmim]Cl) and elucidated the main toxic mechanism of [Cmim]Cl in human cervical carcinoma (Hela) cells. Microstructural analysis revealed that [Cmim]Cl exposure caused the cell membrane breakage, swollen and vacuolated mitochondria, and spherical cytoskeletal structure. Cytotoxicity assays found that [Cmim]Cl exposure increased ROS production, decreased mitochondrial membrane potential, induced cell apoptosis and cell cycle arrest. These results indicated that [Cmim]Cl could induce damage to cellular membrane structure, affect the integrity of cell ultrastructure, cause the oxidative damage and ultimately lead to the inhibition of cell proliferation. Moreover, alterations of biochemical information including the increased ratios of unsaturated fatty acid and carbonyl groups to lipid, and lipid to protein, and the decreased ratios of Amide I to Amide II, and α-helix to β-sheet were observed in [Cmim]Cl treated cells, suggesting that [Cmim]Cl could affect the structure of membrane lipid alkyl chain and cell membrane fluidity, promote the lipid peroxidation and alter the protein secondary structure. The findings from this work demonstrated that membrane structure is the key target, and membrane damage is involved in [Cmim]Cl induced cytotoxicity.