Elafibranor and S217879 induce antioxidative stress response and enhance autophagy.
Human PCLS were generated from the liver of patients with MAFLD (n = 12) and treated with elafibranor (10 μM) or S217879 (3 μM) or vehicle (DMSO, 0.1%) for 2 days. (A) Quantification of total GSH content in human PCLS (GSH/protein content ratio). (B) qPCR analysis of GSTA2, (C) GPX2 and (D) GPX3 expression in human PCLS. (E) Representative western blotting of GSTM2, GPX2 and MGST1 expression. (F) Quantification of GPX2, (G) GSTM2, and (H) MGST1 protein expression. (I) Immunoblot analysis of LC3-II expression in human PCLS (n = 11). Chloroquine (300 μM) was added for the last hour of the culture period. Data are expressed as mean ± SEM. ∗p <0.05; ∗∗p <0.01; ∗∗∗p <0.001; ns, not significant (Wilcoxon paired t test). GPX2, glutathione peroxidase 2; GPX3, glutathione peroxidase 3; GSH, glutatione; GSTA2, glutathione S-transferase alpha-2; GSTM2, glutathione S-transferase Mu 2; LC3, light chain-3; MAFLD, metabolic-associated fatty liver disease; MGST1, microsomal glutathione S-transferase 1; PCLS, precision cut liver slices; qPCR, quantitative PCR.