Dimethyl fumarate reduces hepatocyte senescence following paracetamol exposure

Liver disease is a major cause of premature death. Oxidative stress in the liver represents a key disease driver. Compounds, such as dimethyl fumarate (DMF), can activate the antioxidant response and are used clinically to treat disease. In this study, we tested the protective properties of DMF before or after paracetamol exposure. Following DMF administration, Nrf2 nuclear translocation was tracked at the single-cell level and target gene transactivation confirmed. Next, the protective properties of DMF were examined following paracetamol exposure. Transcriptomic and biochemical analysis revealed that DMF rescue was underpinned by reduced Nf-kappa B and TGF-beta signaling and cell senescence. Following on from these studies, we employed a Zebrafish model to study paracetamol exposure in vivo. We combined a genetically modified Zebrafish model, expressing green fluorescent protein exclusively in the liver, with automated microscopy. Pre-treatment with DMF, prior to paracetamol exposure, led to reduced liver damage in Zebrafish demonstrating protective properties.

Automated summary

Liver disease is a leading cause of premature death, with oxidative stress in the liver being a key driver. The compound dimethyl fumarate (DMF) has been shown to activate antioxidant responses and protect against liver damage. This study demonstrated that DMF could reduce liver damage and cell senescence by inhibiting Nf-κB and TGF-β signaling pathways.