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Biochemical and Molecular Actions of Nutrients

Moderate Iron Overload Enhances Lipid Peroxidation in Livers of Rats, but Does Not Affect NF-B Activation Induced by the Peroxisome Proliferator, Wy-14,643^{1 ,2}

Joan G. Fischer^*3, Howard P. Glauert^**, Taofei Yin^*,4, Mary L. Sweeney-Reeves^*,5, Nicolas Larmonier^**,6 and Marsha C. Black

Departments of ^* Foods and Nutrition and Environmental Health Science, University of Georgia, Athens, GA 30602; and the ^** Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY 40506

³To whom correspondence should be addressed. E-mail: jfischer{at}fcs.uga.edu.

It has been hypothesized that high concentrations of tissue iron may enhance carcinogenesis induced by free radical mechanisms. Wy-14,643 is a peroxisome proliferator that is hepatocarcinogenic in rats. Tumor induction may result in part from excessive production of reactive oxygen species, particularly H₂O₂. The purpose of this study was to examine the effect of iron status on oxidative stress and NF-B activation in livers of rats treated with Wy-14,643. Forty-eight male Sprague–Dawley rats were fed one of four diets (20, 45, 650, 1500 mg Fe/kg diet) for 28 d. At the time of tissue collection, liver iron ranged from 1.4 to 9.9 µmol/g wet tissue in the diet groups. Wy-14,643 (0 or 0.1 g/100 g diet) was added to the diet for the final 10 d of the study. Wy-14,643 doubled the liver weight/body weight ratio (P = 0.0001), which was also increased by iron supplementation (P < 0.01). Iron supplementation increased thiobarbituric acid reactive substances and/or conjugated dienes, but there was no synergism between Wy 14,643 and iron on lipid peroxidation measures. The hepatic DNA binding activity of NF-B was increased in rats administered Wy-14,643. However, differences in liver iron concentration did not alter activation of NF-B in untreated rats or in those treated with Wy-14,643. DNA double-strand breakage was not affected by iron or Wy-14,643. In summary, although moderate changes in iron status altered liver lipid peroxidation, iron did not significantly increase oxidative stress induced by a hepatocarcinogenic peroxisome proliferator.

KEY WORDS: • iron • rats • peroxisome proliferator • oxidative stress • nuclear factor-B

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