Iron increases ethanol toxicity in rat liver.
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.
Stål
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P
Department of Medicine, Karolinska Institute at Huddinge University Hospital, Sweden.
Hultcrantz
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R
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
D000431:Ethanol; D007501:Iron; D000410:Alanine Transaminase; D006909:Hydroxyproline