Iron overload of the liver by trimethylhexanoylferrocene in rats.
Iron-deficient female Wistar rats were fed a diet, which contained 0.5% trimethylhexanoylferrocene, over a 56-week period. This dietary iron loading resulted in a progressive siderosis and enlargement of the liver with a maximum iron content of 947.0 +/- 148.0 mg (vs. 0.07 +/- 0.04 mg in iron deficiency) and a maximum organ weight of 39.4 +/- 6.6 g (vs. 6.9 +/- 1.4 g in iron-deficient control rats). Up to 43 weeks, whole liver iron rose by increase in iron concentration (max. 28.0 +/- 6.1 mg/g wet weight, w.w.) as well as by enlargement of the organ. Afterwards whole liver iron increased solely by ongoing hepatomegaly. At the commencement of iron loading, stainable iron was almost exclusively stored by hepatocytes equally throughout all areas of the liver lobule. Later, the distribution of iron-loaded hepatocytes became strikingly periportal, and, in addition, Kupffer cells as well as sinus-lining endothelia began to store iron. Animals with a liver iron concentration of more than 10.4 +/- 0.75 mg/g w.w. showed no further increase in ferritin and haemosiderin within hepatocytes. Iron-burdened Kupffer cells/macrophages, however, accumulated permanently, hereby forming intrasinusoidal and portal siderotic nodules and areas. First signs of liver damage such as necrosis of single hepatocytes and mild fibrosis began at a liver iron concentration of 14.7 +/- 1.4 mg/g w.w. With advancement of iron loading, focal necrosis of hepatocytes and iron-burdened macrophages took place, and significant perisinusoidal as well as portal fibrosis developed. Cirrhosis, however, the final stage of impairment in iron overload of the liver in humans, could not be induced in this animal model up to now.
Düllmann
J
J
Abteilungen für Neuroanatomie, Universitäts-krankenhaus Eppendorf, Hamburg.
Wulfhekel
U
U
Nielsen
P
P
Heinrich
H C
HC
D000818:Animals; D005260:Female; D005293:Ferritins / Q000032:analysis; D005296:Ferrous Compounds / Q000378:metabolism* / Q000494:pharmacology; D007501:Iron / Q000032:analysis / Q000378:metabolism*; D008099:Liver / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D000075163:Metallocenes; D008854:Microscopy, Electron; D009942:Organometallic Compounds / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D005296:Ferrous Compounds; D000075163:Metallocenes; D009942:Organometallic Compounds; C050224:3,5,5-trimethylhexanoylferrocene; D005293:Ferritins; D007501:Iron