Iron increases ethanol toxicity in rat liver

J Hepatol. 1993 Jan;17(1):108-15. doi: 10.1016/s0168-8278(05)80530-6.


Clinical evidence indicates that patients with iron overload are more susceptible to liver cell damage from alcohol than persons with normal iron stores. Iron may act as a co-factor to catalyze the lipid peroxidation induced by hepatotoxic compounds such as alcohol. To elucidate the role of iron in ethanol-induced hepatocellular damage, we developed a new experimental model in the rat. Following dietary carbonyl iron feeding for 8 weeks, animals were pair-fed a liquid ethanol diet for 4 weeks. In iron-fed animals the liver iron content was 6.4 vs. 0.5 micrograms Fe/mg protein in the controls. Blood alcohol concentrations were similar in all ethanol-fed animals. Serum alanine aminotransferase (ALT) levels were elevated to 269 +/- 49 U/l in the iron+alcohol group compared to 52 +/- 6 U/l in the other groups. There was a strong correlation between ALT levels and hepatic iron content in the ethanol-fed animals. Morphologically, the alcohol-fed rats displayed hepatic steatosis, whereas occasional inflammation and iron in Kupffer cells was seen in the iron+alcohol animals. Ultrastructurally, necrotic hepatocytes and cells phagocytosed by Kupffer cells were only encountered in the iron+alcohol group. Compared to controls, the liver content of hydroxyproline was significantly increased in the iron+alcohol group. No morphological evidence of fibrosis was noted. The present study demonstrates biochemical and morphological evidence of increased hepatocellular damage following the combination of iron and ethanol.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Diet*
  • Drug Synergism
  • Ethanol / blood
  • Ethanol / toxicity*
  • Hydroxyproline / analysis
  • Iron / analysis
  • Iron / pharmacology*
  • Liver / drug effects
  • Liver / pathology*
  • Liver / ultrastructure
  • Male
  • Microscopy, Electron
  • Rats
  • Rats, Sprague-Dawley
  • Reference Values


  • Ethanol
  • Iron
  • Alanine Transaminase
  • Hydroxyproline