S217879 but not elafibranor reduces liver DNA damage and apoptosis.
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) Immunohistochemical analysis of p-H2A.X-positive nuclei (%) on human PCLS sections. Scale bar: 200 μm. (B) Immunoblot analysis of liver p-H2A.X expression in human PCLS. (C) qPCR analysis of RAD51 and (D) XRCC1 expression in human PCLS. (E) Immunohistochemical analysis of cleaved Caspase-3 positive area (%) on human PCLS sections. Scale bar: 200 μm. Data are expressed as mean ± SEM. ∗p <0.05; ∗∗p <0.01; ∗∗∗p <0.001; ns, not significant (Wilcoxon paired t test). MAFLD, metabolic-associated fatty liver disease; PCLS, precision cut liver slices; p-H2A.X, phospho-Histone H2A.X; qPCR, quantitative PCR; XRCC1, X-ray repair cross complementing 1.