Discovery - University of Dundee - Online Publications

Library & Learning Centre

Loss of Nrf2 markedly exacerbates nonalcoholic steatohepatitis

Loss of Nrf2 markedly exacerbates nonalcoholic steatohepatitis

Research output: Contribution to journalArticle

View graph of relations


Research units


Original languageEnglish
Number of pages15
JournalFree Radical Biology and Medicine
Journal publication date2010


Nonalcoholic steatohepatitis (NASH) arises from nonalcoholic fatty liver disease (NAFLD) as a consequence of oxidative stress. Herein we report that the development of NASH is greatly accelerated in mice lacking transcription factor Nrf2 when they are challenged with a methionine- and choline-deficient (MCD) diet. After 14 days of feeding on an MCD diet, livers from Nrf2(-/-) mice showed a substantial increase in macro- and microvesicular steatosis and a massive increase in the number of neutrophil polymorphs, compared to livers from wild-type mice treated similarly. Livers of Nrf2(-/-) mice on the MCD diet suffered More oxidative stress than their wild-type counterparts as assessed by a significant depletion of reduced glutathione that was coupled with increases in oxidized glutathione and malondialdehyde. Furthermore, livers from Nrf2(-/-) mice on the MCD diet suffered heightened inflammation as judged by an similar to 10-fold increase in the amount of nuclear NF-kappa B p65 protein and similar to 5-fold increases in the levels of mRNA for interleukin-1 beta, tumor necrosis factor alpha, cyclooxygenase 2, and inducible nitric oxide synthase compared with livers from similarly treated wild-type mice. Thus, impairment of Nrf2 activity may represent a major risk factor for the evolution of NAFLD to NASH. (C) 2009 Elsevier Inc. All rights reserved.


Library & Learning Centre

Contact | Accessibility | Policy