title: Iron increases ethanol toxicity in rat liver.
abstract: 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.
authors.affiliation: Department of Medicine, Karolinska Institute at Huddinge University Hospital, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Stål
authors.forename: R
authors.initials: R
authors.lastname: Hultcrantz
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D004032:Diet; D004357:Drug Synergism; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D006909:Hydroxyproline / Q000032:analysis; D007501:Iron / Q000032:analysis / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
chemical_list: D000431:Ethanol; D007501:Iron; D000410:Alanine Transaminase; D006909:Hydroxyproline