Zinc supplementation inhibits lipid peroxidation and the development of atherosclerosis in rabbits fed a high cholesterol diet.
Abstract
Developing atherosclerotic lesions in hypercholesterolemic rabbits are depleted in zinc, while iron accumulates. This study examined the influence of zinc supplementation on the development of atherosclerosis and used isotope dilution gas chromatography-mass spectrometry techniques to measure biomarkers of oxidative lipid damage in atherosclerotic rabbit aorta. Our previous method for F(2)-isoprostane measurement was adapted to include the quantitation of cholesterol oxidation products in the same sample. Two groups of New Zealand white rabbits were fed a high cholesterol (1% w/w) diet and one group was also supplemented with zinc (1 g/kg) for 8 weeks. Controls were fed a normal diet. Zinc supplementation did not significantly alter the increase in total plasma cholesterol levels observed in animals fed high cholesterol. However, in cholesterol-fed animals zinc supplementation significantly reduced the accumulation of total cholesterol levels in aorta which was accompanied by a significant reduction in average aortic lesion cross-sectional areas of the animals. Elevated levels of cholesterol oxidation products (5,6-alpha and beta cholesterol epoxides, 7beta-hydroxycholesterol, 7-ketocholesterol) in aorta and total F(2)-isoprostanes in plasma and aorta of rabbits fed a cholesterol diet were significantly decreased by zinc supplementation. Our data indicate that zinc has an antiatherogenic effect, possibly due to a reduction in iron-catalyzed free radical reactions.
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Dysregulation of cholesterol metabolism and oxysterol accumulation are associated with AMD as well as other pathologies involving oxidative stress such as Huntington's disease, atherosclerosis, and cystic fibrosis.
“Dysregulation of cholesterol metabolism and oxysterol accumulation are also associated with AMD as well as other pathologies involving oxidative stress such as Huntington’s disease, atherosclerosis, and cystic fibrosis (Iuliano et al., 2003, 2009; Jenner et al., 2007; Kreilaus et al., 2016).”
From Microtubule-associated protein 1 light chain 3B, (LC3B) is necessary to maintain lipid-mediated homeostasis in the retinal pigment epithelium (2018) · cites this paper as Jenner et al., 2007
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- Authors
- Jenner, A., Ren, M., Rajendran, R., Ning, P., Huat, B. T. K., Watt, F., & Halliwell, B.
- Affiliations
- National University of Singapore (SG)
- Corresponding author
- Jenner, Andrew
- ORCID
- Halliwell, Barry
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2007-02
- Volume
- 42
- Issue
- 4
- Pages
- 559-566
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2069331857
- Cited by
- 96
- References
- 54
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 4 · 2017: 6 · 2016: 3 · 2015: 7 · 2014: 7 · 2013: 6 · 2012: 5
- FWCI
- 6.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Research Online (University of Wollongong) (submittedVersion)
- National University of Singapore (submittedVersion)
- Figshare (submittedVersion)
- Funders
- Biomedical Research Council
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- zinc supplementation, atherosclerosis, lipid peroxidation, high-cholesterol diet, F2-isoprostanes, cholesterol oxidation products, aortic lesions, hypercholesterolemia, antiatherogenic effects, 7-ketocholesterol, 7β-hydroxycholesterol, cholesterol epoxides
- MeSH terms
- Animals, Cholesterol, Dietary, Gas Chromatography-Mass Spectrometry, Rabbits, Zinc, Lipid Peroxidation, Atherosclerosis
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