Hepatotoxicity associated with dietary iron overload in mice.
1. Weanling male CD-1 mice were fed 120 (control), 5000 and 8000 mg of iron kg-1 for seven weeks. The haematocrit (P = 0.265), water consumption (P = 0.170) and percentage body weight ratios of kidney, spleen and heart were not affected by iron supplementation. 2. Iron supplementation reduced weight gain (P = 0.023), increased weight of liver (P = 0.0001), the iron deposition index and concentration of iron in the liver (P < 0.01). A strong correlation between liver iron concentration and level of iron in the diet (r = 0.989) was observed. Histologically, the deposition of iron was restricted to the hepatocytes, Kupffer cells and splenic macrophages. 3. Consumption of 5000 and 8000 mg of iron kg-1 resulted in hepatic damage, as judged by elevated serum alkaline phosphatase and alanine aminotransferase activities (P < 0.05). 4. This study indicates that prolonged feeding of excess dietary iron has the potential to cause hepatic accumulation of iron with resultant liver toxicity, and that mice may be a suitable model to study the mechanisms of dietary iron overload.
Omara
F O
FO
Department of Veterinary Physiological Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada.
Blakley
B R
BR
Wanjala
L S
LS
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000821:Animal Feed; D000818:Animals; D007501:Iron / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000506:poisoning*; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013054:Spectrophotometry, Atomic; D013154:Spleen / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
D007501:Iron; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase