A new NRF2 activator for the treatment of human metabolic dysfunction-associated fatty liver disease.

ABSTRACT:

Background & aims

Oxidative stress triggers metabolic-associated fatty liver disease (MAFLD) and fibrosis. Previous animal studies demonstrated that the transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2), the master regulator of antioxidant response, protects against MAFLD and fibrosis. S217879, a next generation NRF2 activator has been recently shown to trigger diet-induced steatohepatitis resolution and to reduce established fibrosis in rodents. Our aim was to evaluate the therapeutic potential of S217879 in human MAFLD and its underlying mechanisms using the relevant experimental 3D model of patient-derived precision cut liver slices (PCLS).

Methods

We treated PCLS from 12 patients with varying stages of MAFLD with S217879 or elafibranor (peroxisome p

SUBMITTER: Hammoutene A 

PROVIDER: S-EPMC10472315 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature