The long-acting parenteral iron chelator, hydroxyethyl starch-deferoxamine, fails to protect against alcohol-induced liver injury in rats

We studied the effect of the long-acting parenteral iron chelator, hydroxyethyl starch deferoxamine (HES-DFO) on liver nonheme iron, lipid peroxidation and pathologic changes in the liver in the intragastric feeding rat model for alcoholic liver disease. Male Wistar rats (225-250 g) were fed liquid diet and ethanol for 2 months. In control pair-fed animals, ethanol was isocalorically replaced by dextrose. Two additional groups of animals (dextrose and ethanol fed) received HES-DFO (25 mg deferoxamine equivalents/kg, three times a week). The blood ethanol level in the ethanol-fed animals was maintained between 150 and 350 mg/dl. For each animal, the levels of hepatic nonheme iron, lipid peroxidation and pathologic changes were evaluated. Ethanol administration caused fatty liver; necrosis and inflammation. Addition of HES-DFO to the ethanol diet increased the severity of pathologic changes, particularly necrosis and inflammation. The nonheme iron in alcohol-fed animals was significantly higher (18.3 +/- 4.3 mu g liver) than in pair-fed dextrose controls (12.5 +/- 1.5 mu g, P < .05). Addition of HES-DFO significantly increased nonheme iron levels in the dextrose-fed rats (17.1 +/- 2.0 mu g/g, P < .02) but not in ethanol-fed rats (20.0 +/- 2.0). Ethanol increased levels of conjugated dienes; these levels were not altered by HES-DFO. The most significant observations in this study were: 1) the higher hepatic nonheme iron content in ethanol-fed rats compared with pair-fed dextrose controls; 2) the absence of changes in hepatic nonheme iron levels or lipid peroxidation in ethanol-fed groups treated with HES-DFO; and 3) the worsening of liver injury in ethanol-fed rats by HES-DFO.