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. Th is study identifies rat models of alcohol abuse that closely mimic these di sturbances, 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 analy zed for ferritin, transferrin, and iron levels, and the transferrin iron sa turation and ferritin:transferrin ratios were calculated. Liver iron concen trations were also determined. Serum transferrin levels were elevated in an imals fed ethanol for 8 weeks in pair-feeding and agar-block feeding protoc ols, but reduced in rats with cirrhosis. Serum ferritin concentration was r educed in rats fed ethanol in the liquid diet, but increased in rats consum ing ethanol in agar blocks, in rats pair-fed the liquid control diet, and i n rats with cirrhosis. This finding was mirrored by liver nonheme iron conc entrations 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 l iquid diet, but not when ethanol was ingested from agar blacks. The develop ment of cirrhosis resulted in elevated liver iron concentrations and double d ferritin:transferrin ratios. It is concluded that these models may be use d to study disturbances in iron homeostasis that occur during alcohol abuse and the (subsequent) development of liver disease. (C) 2001 Elsevier Scien ce Inc. All rights reserved.