Use of rat models to mimic alterations in iron homeostasis during human alcohol abuse and cirrhosis

With alcoholism, there are marked disturbances in iron homeostasis that are linked to alterations in serum transferrin and ferritin concentrations. This study identifies rat models of alcohol abuse that closely mimic these disturbances, Male rats were placed in one of the following three protocols: (1) pair-feeding of liquid diets for 1-8 weeks; (2) agar-block feeding for 8 weeks; or (3) generation of cirrhosis with CCL4. Serum samples were analyzed for ferritin, transferrin, and iron levels, and the transferrin iron saturation and ferritin:transferrin ratios were calculated. Liver iron concentrations were also determined. Serum transferrin levels were elevated in animals fed ethanol for 8 weeks in pair-feeding and agar-block feeding protocols, but reduced in rats with cirrhosis. Serum ferritin concentration was reduced in rats fed ethanol in the liquid diet, but increased in rats consuming ethanol in agar blocks, in rats pair-fed the liquid control diet, and in rats with cirrhosis. This finding was mirrored by liver nonheme iron concentrations in all experimental groups, but not in the corresponding control groups. Serum iron levels were significantly elevated only in rats fed the liquid control diet. There was a progressive decrease in transferrin iron saturation and ferritin:transferrin ratios for animals fed ethanol in the liquid diet, but not when ethanol was ingested from agar blacks. The development of cirrhosis resulted in elevated liver iron concentrations and doubled ferritin:transferrin ratios. It is concluded that these models may be used to study disturbances in iron homeostasis that occur during alcohol abuse and the (subsequent) development of liver disease. (C) 2001 Elsevier Science Inc. All rights reserved.