Zinc supplementation inhibits lipid peroxidation and the development of atherosclerosis in rabbits fed a high cholesterol diet.
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.
Jenner
Andrew
A
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, MD7, 8 Medical Drive, Singapore 117597. bchjam@nus.edu.sg
Ren
Minqin
M
Rajendran
Reshmi
R
Ning
Pan
P
Huat
Benny Tan Kwong
BT
Watt
Frank
F
Halliwell
Barry
B
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism / Q000517:prevention & control*; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D008401:Gas Chromatography-Mass Spectrometry; D015227:Lipid Peroxidation / Q000187:drug effects*; D011817:Rabbits; D015032:Zinc / Q000008:administration & dosage* / Q000494:pharmacology
D002791:Cholesterol, Dietary; D015032:Zinc