THE ORAL IRON CHELATOR, 1,2-DIMETHYL-3-HYDROXYPYRID-4-ONE REDUCES HEPATIC-FREE IRON, LIPID-PEROXIDATION AND FAT ACCUMULATION IN CHRONICALLYETHANOL-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 accumu lation in the intragastric feeding rat model for alcoholic liver disea se 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 (dextros e and ethanol-fed) received L1 (75 mg/kg/day for 30 days). The blood e thanol 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 alc ohol-fed animals was significantly higher (416 +/- 15 nmol/g of liver) than in pair-fed dextrose controls (346 +/- 18.5 nmol/g, P<.05). Anim als 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 n onheme 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.