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.
Sadrzadeh
S M
SM
Department of Pathology, New England Deaconess Hospital, Boston, MA 02215.
Nanji
A A
AA
Price
P L
PL
D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D000077543:Deferiprone; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011728:Pyridones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000378:metabolism*
D007502:Iron Chelating Agents; D011728:Pyridones; D014280:Triglycerides; D000077543:Deferiprone; D007501:Iron