ALCOHOL MEDIATES INCREASES IN HEPATIC AND SERUM NONHEME IRON STORES IN A RAT MODEL FOR ALCOHOL-INDUCED LIVER-INJURY

The notion that prolonged ethanol consumption promotes hepatocellular damage through interactions with iron was evaluated in rats fed ethano l with or without supplemental dietary carbonyl iron, The individual a nd combined pro-oxidant potential of these agents was evaluated in ter ms of their ability to perturb iron homeostasis and initiate hepatocel lular 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 carbon yl iron (Alcohol + Iron group), or a diet containing carbohydrate-deri ved isocaloric calories (Control group), Hepatic and serum nonheme iro n stores were significantly elevated (p < 0.05) in all treatment group s, compared with the Controls, Catalytically active low-molecular weig ht iron was detected in rats consuming alcohol and was markedly elevat ed (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), Significan t hepatic fatty infiltration, increased hydroxyproline content, and pe rturbations in reduced glutathione were also observed in the Alcohol a nd Iron treatment groups. Histochemical assessment of hepatic iron seq uestration revealed that alcohol feeding resulted in deposition of fer ric iron in the centrilobular area of the liver lobule, This unique al cohol-mediated iron deposition was histologically graded above Control group and was observed in both hepatocytes acid Kupffer cells, Data p resented herein suggest that alcohol alone or in combination with iron results in rather specific lobular patterns of hepatic iron depositio n relevant to iron overload observed in human alcoholics, Furthermore, data suggest that alcohol- and iron-initiated prefibrotic events occu r before extensive hepatocellular necrosis.