@article{10.37349/edd.2025.100581,
abstract = {Aim: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a widespread chronic liver condition associated with liver inflammation, fibrosis, and various metabolic disorders. Although cholic acid (CA), a primary bile acid (BA), is known to reduce steatosis when added to a high-fat diet, it may exacerbate hepatocellular injury by promoting oxidative stress and inflammation. Therefore, regulating BA-induced liver toxicity is crucial. Dimethyl fumarate (DMF) is an FDA-approved drug known to activate the nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2), a transcription factor that induces cytoprotective genes involved in cellular stress. The present study aimed to investigate whether DMF supplementation could attenuate CA-induced liver injury in high-fat diet-fed mice. Methods: To induce liver injury, high-fat diet with and without CA were compared for liver damage and liver fat gain. Following the establishment of the toxic but antisteatotic effect of CA, C57BL/6j mice were fed a high-fat diet supplemented with 0.5% CA (HFDCA) with or without DMF (0.3 mg/mL or 0.6 mg/mL), which was administered via drinking water for 7 weeks. Results: CA was found to be an accelerator of high-fat diet to induce liver damage, but prevented liver fat accumulation. HFDCA mice showed signs of liver damage, including elevated liver enzymes and liver enlargement. However, DMF treatment activated the Nrf2 pathway and partially mitigated the hepatotoxic effect of CA/high-fat diet, although some doses exhibited pro-oxidant effects. Conclusions: The findings suggest that DMF, as an activator of Nrf2, has potential as a therapeutic agent for liver diseases related to high-fat diets and BA-induced injury, though careful dosage management is crucial to maximize its benefits and mitigate BA toxicity.},
author = {Abu-Halaka, Diana and Rauchbach, Einat and Zeigerman, Haim and Tirosh, Oren},
doi = {10.37349/edd.2025.100581},
journal = {Exploration of Digestive Diseases},
elocation-id = {100581},
title = {DMF, an activator of Nrf2, could mitigate cholic-acid-induced liver damage in high-fat diet},
url = {https://www.explorationpub.com/Journals/edd/Article/100581},
volume = {4},
year = {2025}
}