Histopathological evaluation of liver, pancreas, spleen, and heart from iron-overloaded Sprague-Dawley rats.
The effects of increasing dietary levels of Fe on the histopathology of liver, pancreas, spleen, and heart were examined in a rat model for iron overload. Sprague-Dawley rats were fed diets containing 35, 350, 3,500, or 20,000 micrograms Fe/g, and, after 12 wk, there was a direct correlation between increased liver nonheme Fe and lipid peroxidation measured by the lipid-conjugated diene assay. Histopathological examination of tissues revealed the following: (a) hepatocellular hemosiderosis in all groups of rats, with a dose-related accumulation of cytoplasmic Fe-positive material predominantly in hepatocytes located in the periportal region (Zone 1), (b) myocardial degeneration and necrosis (cardiomyopathy) with hemosiderin in interstitial macrophages or in myocardial fibers of animals with heart damage, (c) splenic lymphoid atrophy affecting the marginal zone of the white pulp and hemosiderin deposition in the sinusoidal macrophages, and (d) pancreatic atrophy with loss of both the endocrine and exocrine pancreatic tissue in those animals receiving 3,500 and 20,000 micrograms Fe/g of diet. The toxic effects of Fe overload in this rat model include cellular apoptosis or necrosis in heart, spleen, and pancreas and, when coupled with the findings on lipid peroxidation, suggests that oxidative stress is involved in the pathogenesis of the lesions.
Whittaker
P
P
Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, D.C. 20204, USA.
Hines
F A
FA
Robl
M G
MG
Dunkel
V C
VC
D000818:Animals; D006321:Heart / Q000187:drug effects*; D019190:Iron Overload / Q000473:pathology*; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008297:Male; D009206:Myocardium / Q000473:pathology*; D010179:Pancreas / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects / Q000473:pathology*