Effects of long-term ethanol ingestion on hepatic iron metabolism in two mouse strains

The mechanisms responsible for dysregulation of iron metabolism in response to ethanol ingestion are poorly understood. Relatively brief ethanol exposures in rodents are associated with reduced hepatic hepcidin expression without increases in hepatic iron content. This study evaluated the effects of long-term ethanol treatment on hepatic iron metabolism in two mouse strains. Ethanol was administered in the drinking water to C57BL/6 and BALB/c mice for up to 11 months. Hepatic histology and iron concentrations (HIC) were assessed, along with expression of relevant genes and proteins by real-time RT-PCR and western blot, respectively. The livers of ethanol-consuming mice of both strains showed mild steatosis without inflammation or fibrosis. Stainable hepatocyte iron was modestly increased in both strains ingesting ethanol, although hepatic iron concentrations were significantly higher only in C57BL/6 mice. Long-term ethanol did not affect hepcidin mRNA (Hamp1 or Hamp2) in either strain, nor was the expression of several oxidative stress-responsive genes (glutamate cysteine ligase, gamma-glutamyl transpeptidase, heme oxygenase-1 and growth differentiation factor 15) altered in response to ethanol, suggesting that oxidative stress and suppression of hepcidin expression in short-term ethanol feeding models may be transient phenomena that resolve as mice adapt to ethanol exposure. This murine model of chronic ethanol ingestion demonstrates modest increases in hepatic iron without changes in hepcidin expression, markers of oxidative stress or significant histologic liver injury. Further investigations are needed to characterize the mechanisms of dysregulated iron metabolism resulting from chronic ethanol ingestion.

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Work Title Effects of long-term ethanol ingestion on hepatic iron metabolism in two mouse strains
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Open Access
Creators
  1. Steven A. Bloomer
  2. Kimberly A. Broadhurst
  3. M. Maleah Mathahs
  4. Kyle E. Brown
License In Copyright (Rights Reserved)
Work Type Article
Publisher
  1. Clinical and Experimental Pharmacology and Physiology
Publication Date April 1, 2021
Publisher Identifier (DOI)
  1. https://doi.org/10.1111/1440-1681.13445
Deposited November 17, 2021

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Version 1
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  • Created
  • Added cep13445_accepted.pdf
  • Added Creator Steven A. Bloomer
  • Added Creator Kimberly A. Broadhurst
  • Added Creator M. Maleah Mathahs
  • Added Creator Kyle E. Brown
  • Published
  • Updated
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