title: Biochemical and biophysical investigations of the ferrocene-iron-loaded rat. An animal model of primary haemochromatosis.
abstract: Male Wistar rats fed with ferrocene had high hepatic iron loading (7.24 +/- 1.97 mg Fe/g tissue) after 6 weeks, principally located in lysosomes, which was comparable to the levels and distribution determined in human haemochromatosis. The two iron-storage proteins, ferritin and haemosiderin were isolated from the livers of the ferrocene-loaded rats and their iron cores were investigated by Mössbauer spectroscopy and inductively coupled plasma-emission spectrometry. Ferrihydrite was the predominant form of iron present in both ferritin and haemosiderin, while haemosiderin contained higher amounts of phosphorus, magnesium, calcium and barium, then either normal or ferrocene-loaded ferritin. Free-radical-mediated damage in the iron-loaded livers was inferred by the significant depletion of alpha-tocopherol in both the livers and subcellular hepatic lysosomal fraction, which inversely correlated with the increasing iron content (r = -0.61; P less than 0.05) and was associated with increased fragility of the lysosomal membranes.
authors.affiliation: Department of Clinical Biochemistry, King's College School of Medicine and Dentistry, London, England.
authors.forename: R J
authors.initials: RJ
authors.lastname: Ward
authors.forename: A L
authors.initials: AL
authors.lastname: Florence
authors.forename: D
authors.initials: D
authors.lastname: Baldwin
authors.forename: C
authors.initials: C
authors.lastname: Abiaka
authors.forename: F
authors.initials: F
authors.lastname: Roland
authors.forename: M H
authors.initials: MH
authors.lastname: Ramsey
authors.forename: D P
authors.initials: DP
authors.lastname: Dickson
authors.forename: T J
authors.initials: TJ
authors.lastname: Peters
authors.forename: R R
authors.initials: RR
authors.lastname: Crichton
mesh_terms: D000818:Animals; D002458:Cell Fractionation; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D005293:Ferritins / Q000378:metabolism; D005296:Ferrous Compounds / Q000633:toxicity*; D006432:Hemochromatosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D006485:Hemosiderin / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D000075163:Metallocenes; D009942:Organometallic Compounds / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D015204:Spectroscopy, Mossbauer; D014810:Vitamin E / Q000378:metabolism
chemical_list: D005296:Ferrous Compounds; D000075163:Metallocenes; D009942:Organometallic Compounds; D014810:Vitamin E; D005293:Ferritins; D006485:Hemosiderin; D007501:Iron; C004998:ferrocene