title: Elevated oxidative stress, iron accumulation around microvessels and increased 4-hydroxynonenal immunostaining in zone 1 of the liver acinus in hypercholesterolemic rabbits.
abstract: Rabbits were fed a diet containing 1% cholesterol for 8 weeks and the levels of iron and oxidized lipids in liver analysed using atomic absorption spectroscopy and gas chromatography-mass spectrometry. A non-significant trend to an increase in iron level, but significant increases in the lipid peroxidation products, F(2)-isoprostanes and the cholesterol oxidation products 7 beta hydroxycholesterol, 7 ketocholesterol and cholesterol 5,6-alpha epoxide were detected in the liver of the cholesterol-fed rabbits. Histological analysis showed greater accumulation of lipids by Sudan red labelling in hepatocytes of zone I than zones II and III of the liver acinus. The increase in lipids coincided with an increase in iron staining in macrophages around liver microvessels and increased immunostaining to melanotransferrin and the lipid peroxidation product, 4-hydroxynonenal (4-HNE), in zone 1. The results are suggestive of microvascular damage associated with iron accumulation and oxidative stress in the liver during hypercholesterolemia.
authors.affiliation: Department of Anatomy, National University of Singapore, Singapore.
authors.forename: Wei-Yi
authors.initials: WY
authors.lastname: Ong
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Jenner
authors.forename: Ning
authors.initials: N
authors.lastname: Pan
authors.forename: Choon-Nam
authors.initials: CN
authors.lastname: Ong
authors.forename: Barry
authors.initials: B
authors.lastname: Halliwell
mesh_terms: D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D006937:Hypercholesterolemia / Q000378:metabolism*; D007501:Iron / Q000097:blood / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000098:blood supply / Q000378:metabolism*; D008854:Microscopy, Electron; D008859:Microscopy, Polarization; D055806:Microvessels / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits
chemical_list: D000447:Aldehydes; D002791:Cholesterol, Dietary; D002784:Cholesterol; D007501:Iron; C027576:4-hydroxy-2-nonenal