Effect of iron overload and dietary fat on indices of oxidative stress and hepatic fibrogenesis in rats

Kyle E Brown; Phyllis A Dennery; Lisa A Ridnour; Claus J Fimmel; Raleigh D Kladney; Elizabeth M Brunt; Douglas R Spitz

doi:10.1034/j.1600-0676.2003.00832.x

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Effect of iron overload and dietary fat on indices of oxidative stress and hepatic fibrogenesis in rats

Journal article

Peer reviewed

Effect of iron overload and dietary fat on indices of oxidative stress and hepatic fibrogenesis in rats

Kyle E Brown, Phyllis A Dennery, Lisa A Ridnour, Claus J Fimmel, Raleigh D Kladney, Elizabeth M Brunt and Douglas R Spitz

Liver international, Vol.23(4), pp.232-242

08/2003

DOI: 10.1034/j.1600-0676.2003.00832.x

PMID: 12895262

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Abstract

Oxidative stress is presumed to play an important role in hepatic fibrogenesis. Diets high in polyunsaturated fatty acids (PUFA) enhance fibrosis and have been associated with increased oxidative damage in some models of liver injury. The aim of this study was to determine the effects of dietary fat of varying PUFA content on iron-induced oxidative stress and fibrosis. Rats were given parenteral iron and diets supplemented with coconut oil, safflower oil or menhaden oil. Hepatic iron overload was associated with induction of heme oxygenase-1, a sensitive indicator of oxidative stress, and with modest increases in hydroxyproline and procollagen I mRNA levels without histologically evident fibrosis, all of which were unaffected by dietary fat. In addition, iron loading was associated with increases in cysteine, gamma-glutamylcysteine and glutathione. Dietary fat brought about the expected alterations in peroxidizability, but did not alter indices of oxidative damage. These data highlight the distinction between oxidative stress and oxidative damage and suggest that the former is not sufficient to elicit overt fibrosis. Furthermore, while hepatic iron overload leads to oxidative stress, there is an associated upregulation of antioxidant defenses involving thiol metabolism that may be a critical factor limiting the accumulation of oxidative damage.

Liver Cirrhosis, Experimental - diet therapy

Liver - pathology

Liver - enzymology

Oxidative Stress

Glutathione - metabolism

Hydroxyproline - biosynthesis

Male

RNA, Messenger - metabolism

Immunoenzyme Techniques

Collagen Type I - genetics

Heme Oxygenase (Decyclizing) - biosynthesis

Iron Overload - metabolism

Liver - drug effects

Liver Cirrhosis, Experimental - pathology

Heme Oxygenase-1

Cysteine - metabolism

Dipeptides - metabolism

Heme Oxygenase (Decyclizing) - genetics

Rats

Rats, Sprague-Dawley

Iron, Dietary - toxicity

Collagen Type I - biosynthesis

Hydroxyproline - genetics

Animals

Dietary Fats, Unsaturated - administration & dosage

Liver Cirrhosis, Experimental - metabolism

Details

Title: Subtitle: Effect of iron overload and dietary fat on indices of oxidative stress and hepatic fibrogenesis in rats
Creators: Kyle E Brown - Gastroenterology Section, John Cochran VAMC, St. Louis, MO, USA. kyle-brown@uiowa.edu
Phyllis A Dennery
Lisa A Ridnour
Claus J Fimmel
Raleigh D Kladney
Elizabeth M Brunt
Douglas R Spitz
Resource Type: Journal article
Publication Details: Liver international, Vol.23(4), pp.232-242
Publisher: United States
DOI: 10.1034/j.1600-0676.2003.00832.x
PMID: 12895262
ISSN: 1478-3223
eISSN: 1478-3231
Grant note: HL-51469 / NHLBI NIH HHS F32ES05781 / NIEHS NIH HHS HL-52701 / NHLBI NIH HHS
Language: English
Date published: 08/2003
Academic Unit: Gastroenterology and Hepatology; Pathology; Radiation Oncology; Internal Medicine
Record Identifier: 9984047652302771

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