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

First Author  Lemmens KJ Year  2015
Journal  Biochem Biophys Res Commun Volume  456
Issue  1 Pages  179-82
PubMed ID  25462563 Mgi Jnum  J:220261
Mgi Id  MGI:5634045 Doi  10.1016/j.bbrc.2014.11.055
Citation  Lemmens KJ, et al. (2015) The flavonoid monoHER promotes the adaption to oxidative stress during the onset of NAFLD. Biochem Biophys Res Commun 456(1):179-82
abstractText  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.
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