Moderate iron overload enhances lipid peroxidation in livers of rats, but does not affect NF-kappaB activation induced by the peroxisome proliferator, Wy-14,643.
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 H(2)O(2). The purpose of this study was to examine the effect of iron status on oxidative stress and NF-kappaB 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 micro mol/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-kappaB was increased in rats administered Wy-14,643. However, differences in liver iron concentration did not alter activation of NF-kappaB 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.
Fischer
Joan G
JG
Departments of Foods and Nutrition, University of Georgia, Athens, GA 30602, USA. jfischer@fcs.uga.edu
Glauert
Howard P
HP
Yin
Taofei
T
Sweeney-Reeves
Mary L
ML
Larmonier
Nicolas
N
Black
Marsha C
MC
D000818:Animals; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D019190:Iron Overload / Q000378:metabolism*; D019266:Iron, Dietary / Q000008:administration & dosage / Q000009:adverse effects; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008113:Liver Neoplasms / Q000209:etiology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D019266:Iron, Dietary; D016328:NF-kappa B; D020025:Peroxisome Proliferators; D011743:Pyrimidines; D017392:Thiobarbituric Acid Reactive Substances; C006253:pirinixic acid; D004247:DNA