The oral iron chelator, 1,2-dimethyl-3-hydroxypyrid-4-one reduces hepatic- free iron, lipid peroxidation and fat accumulation in chronically ethanol- fed rats

The effect of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) on liver nonheme iron, lipid peroxidation and hepatic fat accumulation in the intragastric feeding rat model for alcoholic liver disease was studied. Male Wistar rats (225-250 g) were fed liquid diet and ethanol for 1 month. In control pair-fed animals, ethanol was replaced isocalorically by dextrose. Two additional groups of animals (dextrose and ethanol-fed) received L1 (75 mg/kg/day for 30 days). 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 triglyceride were evaluated. The nonheme iron in alcohol-fed animals was significantly higher (416 ± 15 nmol/g of liver) than in pair-fed dextrose controls (346 ± 18.5 nmol/g, P < .05). Animals fed ethanol and L1 had significantly lower nonheme iron (364 ± 9.3 nmol/g) than rats fed ethanol alone (P < .05). L1 had no effect on nonheme iron levels in dextrose-fed controls. The importance of iron in lipid peroxidation in this model is shown by the positive correlation between the nonheme iron levels and microsomal conjugated dienes (r = 0.67, P < .02) and liver thiobarbituric acid reactive substances (r = 0.62, P < .05). The most significant observations in this study were: 1) the higher hepatic nonheme iron content in ethanol-fed rats compared to pair-fed dextrose controls; 2) lower nonheme iron and liver fat in the ethanol-fed rats treated with L1; and 3) the significant positive correlation between the liver nonheme and lipid peroxidation.