This work was supported by Grant AA-09300 from the National Institute on Alcohol Abuse and Alcoholism and by a supplement to that grant awarded to L.G.V.
Alcohol Mediates Increases in Hepatic and Serum Nonheme Iron Stores in a Rat Model for Alcohol-Induced Liver Injury
Article first published online: 11 APR 2006
Alcoholism: Clinical and Experimental Research
Volume 20, Issue 8, pages 1352–1361, November 1996
How to Cite
Valerio, L. G., Parks, T. and Petersen, D. R. (1996), Alcohol Mediates Increases in Hepatic and Serum Nonheme Iron Stores in a Rat Model for Alcohol-Induced Liver Injury. Alcoholism: Clinical and Experimental Research, 20: 1352–1361. doi: 10.1111/j.1530-0277.1996.tb01134.x
- Issue published online: 11 APR 2006
- Article first published online: 11 APR 2006
- Received for publication April 10, 1996; accepted July 22, 1996
- Alcoholic Liver Disease;
The notion that prolonged ethanol consumption promotes hepatocellular damage through interactions with iron was evaluated in rats fed ethanol with or without supplemental dietary carbonyl iron. The individual and combined pro-oxidant potential of these agents was evaluated in terms of their ability to perturb iron homeostasis and initiate hepatocellular injury. Sprague-Dawely rats received a high fat liquid diet for 8 weeks supplemented with 35% ethanol-derived calories (Alcohol group), 0.02 to 0.04% (w/v) carbonyl iron (Iron group), ethanol plus carbonyl iron (Alcohol + Iron group), or a diet containing carbohydrate-derived isocaloric calories (Control group). Hepatic and serum nonheme iron stores were significantly elevated (p < 0.05) in all treatment groups, compared with the Controls. Catalytically active low-molecular weight iron was detected in rats consuming alcohol and was markedly elevated (p < 0.05) in rats ingesting iron alone or iron in combination with alcohol. Elevations in serum ALT indicated significant hepatocellular injury in rats ingesting only alcohol, but was most prominent in the rats consuming ethanol in combination with iron (p < 0.05). Significant hepatic fatty infiltration, increased hydroxyproline content, and perturbations in reduced glutathione were also observed in the Alcohol and Iron treatment groups. Histochemical assessment of hepatic iron sequestration revealed that alcohol feeding resulted in deposition of ferric iron in the centrilobular area of the liver lobule. This unique alcohol-mediated iron deposition was histologically graded above Control group and was observed in both hepatocytes and Kupffer cells. Data presented herein suggest that alcohol alone or in combination with iron results in rather specific lobular patterns of hepatic iron deposition relevant to iron overload observed in human alcoholics. Furthermore, data suggest that alcohol- and iron-initiated prefibrotic events occur before extensive hepatocellular necrosis.