CYP3A4 and microRNA‐122 are involved in the apoptosis of HepG2 cells induced by ILs 1‐decyl‐3‐methylimidazolium bromide

Abstract

Ionic liquids (ILs) as green alternatives for volatile organic solvents are increasingly used in commercial applications. It is necessary to explore the cytotoxic mechanism of ILs to reduce the risk to human health. For this purpose, cell viability, apoptosis, cytochrome P450 3A4 (CYP3A4), glucose transporter type 2 (GLUT2), and microRNA‐122 (miR‐122) gene expression in HepG2 cells was evaluated after IL exposure. The results showed that ILs reduced the viability of HepG2 cells through apoptotic cell death. Moreover, ILs markedly upregulated the transcription and protein levels of CYP3A4, but did not affect the expression of GLUT2 in either messenger RNA level or protein level. Finally, ILs increased the expression of miR‐122 and inhibition of miR‐122 with miR‐122 inhibitor blocked ILs‐induced apoptosis in HepG2 cells. This finding may contribute to an increased understanding of the in vitro molecular toxicity mechanism of ILs to further understand IL‐related human health risks.

Potential for cardiac toxicity with methylimidazolium ionic liquids

“…Future studies should examine the effects of lower concentrations of MILs in order to identify their NOACs. Based on in vitro studies with a variety of cell types, in terms of mechanism(s), cell death in response to MILs appears broadly to be associated with mitochondrial dysfunction, oxidative stress and apoptosis ( Li et al, 2012 , Jing et al, 2013 ; Li et al, 2015 ; Li et al, 2015 ; Probert et al, 2018 ; Ma et al, 2018 ; Li et al, 2020 ). Preliminary studies in HL-1 cells suggest a similar mechanism (unpublished observations).…”