A corn oil-based diet protects against combined ethanol and iron-induced liver injury in a mouse model of hemochromatosis

Tan, Terrence C. H., Crawford, Darrell H. G., Jaskowski, Lesley A., Murphy, Therese L., Santrampurwala, Nishreen, Crane, Denis, Clouston, Andrew D., Subramaniam, V. Nathan, Anderson, Gregory J. and Fletcher, Linda M. (2013) A corn oil-based diet protects against combined ethanol and iron-induced liver injury in a mouse model of hemochromatosis. Alcoholism-Clinical and Experimental Research, 37 10: 1619-1631. doi:10.1111/acer.12155


Author Tan, Terrence C. H.
Crawford, Darrell H. G.
Jaskowski, Lesley A.
Murphy, Therese L.
Santrampurwala, Nishreen
Crane, Denis
Clouston, Andrew D.
Subramaniam, V. Nathan
Anderson, Gregory J.
Fletcher, Linda M.
Title A corn oil-based diet protects against combined ethanol and iron-induced liver injury in a mouse model of hemochromatosis
Journal name Alcoholism-Clinical and Experimental Research   Check publisher's open access policy
ISSN 0145-6008
1530-0277
Publication date 2013-10
Year available 2013
Sub-type Article (original research)
DOI 10.1111/acer.12155
Open Access Status
Volume 37
Issue 10
Start page 1619
End page 1631
Total pages 13
Place of publication Hoboken, NJ, United States
Publisher Wiley-Blackwell
Collection year 2014
Language eng
Formatted abstract
Background
Combined iron overload and alcohol may promote synergistic chronic liver injury and toxicity. The role of specific dietary fats in influencing the development of co-toxic alcoholic liver disease needs further evaluation and is investigated in this study.

Methods
Wild-type (WT) and the iron-loaded Hfe-null (Hfe−/−) mice were fed chow (CC), a AIN-93G standard control (SC), or a corn oil–modified, AIN-93G-based (CO) diet with or without the addition of 20% ethanol (EtOH) in the drinking water for 8 weeks and assessed for liver injury.

Results
WT mice on CC, SC, and CO diets had no liver injury, although mild steatosis developed in the SC and CO groups. The addition of EtOH resulted in mild steatohepatitis in WT mice fed SC but not those on a CO diet. EtOH administration in Hfe−/− animals on the CC and SC diets caused marked oxidative stress, inflammatory activity, and subsinusoidal and portal–portal tract linkage fibrosis with significant up-regulation of genes involved in cellular stress signaling and fibrogenic pathways. These effects were abrogated in the CO-fed mice, despite elevated serum EtOH levels and hepatic iron concentrations, reduced hepatic glutathione and mitochondrial superoxide dismutase activities. Feeding with the CO diet led to increased hepatic glutathione peroxidase and catalase activities and attenuated alcohol-induced hepatic steatosis in the Hfe−/− animals. Iron and EtOH feeding markedly reduced p-STAT3 and p-AMPK protein levels, but this effect was significantly attenuated when a CO diet was consumed.

Conclusions
A CO-based diet is protective against combined EtOH- and iron-induced liver toxicity, likely via attenuation of hepatic steatosis and oxidative stress and may have a role in the prevention of fibrosis development in chronic liver disease.
Keyword Iron overload
Liver fibrosis
Hepatotoxicity
Alcoholic liver disease
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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