The flavonoid monoHER promotes the adaption to oxidative stress during the onset of NAFLD.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. An evidence-based pharmacological treatment for NAFLD is still lacking, but flavonoids have shown therapeutic potential. The present study was designed to investigate the effect of the flavonoid monoHER on the onset of NAFLD in Ldlr(-/-) mice on a high-fat and high-cholesterol diet. The focus was put on the effect on oxidative stress as well as the adaptive response. Wild type mice served as a control and the effect of monoHER was compared to that of a placebo. In the Ldlr(-/-) group, monoHER provided only a mild protection against oxidative stress. In the placebo Ldlr(-/-) group an adaptive response elicited by the NRF2 antioxidant defense system was observed, evidenced by a higher HO-1 and Gpx3 gene expression, as well as an increased redox status, evidenced by the higher GSH/GSSG ratio. In the monoHER treated Ldlr(-/-) group both the adaptive response as well as the increase in redox status tended to be higher, although this did not reach significance on a group level. Unexpectedly, a strong within animal relationship was found that links a high adaptive response to a low redox status in the monoHER Ldlr(-/-) group. This correlation was absent in the placebo and wild type group. The concept that emerges is that a thiol-reactive oxidation product of monoHER, formed during oxidative stress, selectively induces the NRF2 pathway and enforces the endogenous antioxidant shield, to provide protection against NAFLD.

• Authors: Kristien J A Lemmens, Bregje van de Wier, Ger H Koek, Eleonore Köhler, Marie-José Drittij, Wim J F van der Vijgh, Aalt Bast, Guido R M M Haenen
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 456 Issue 1 Pg. 179-82 (Jan 02 2015) ISSN: 1090-2104 [Electronic] United States
• PMID: 25462563 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• 7-monohydroxyethylrutoside
• Antioxidants
• Flavonoids
• Hydroxyethylrutoside
• Membrane Proteins
• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• Reactive Oxygen Species
• Receptors, LDL
• Gpx3 protein, mouse
• Glutathione Peroxidase
• Heme Oxygenase-1
• Hmox1 protein, mouse

Topics

• Animals
• Antioxidants (pharmacology)
• Female
• Flavonoids (pharmacology)
• Gene Expression Regulation
• Glutathione Peroxidase (metabolism)
• Heme Oxygenase-1 (metabolism)
• Hydroxyethylrutoside (analogs & derivatives, pharmacology)
• Membrane Proteins (metabolism)
• Mice
• Mice, Inbred C57BL
• NF-E2-Related Factor 2 (metabolism)
• Non-alcoholic Fatty Liver Disease (drug therapy)
• Oxidation-Reduction
• Oxidative Stress (drug effects)
• Reactive Oxygen Species
• Receptors, LDL (genetics)