title: Effects of alpha-tocopherol and astaxanthin on LDL oxidation and atherosclerosis in WHHL rabbits.
abstract: The aim of this study was to evaluate the influence of -tocopherol and astaxanthin on low-density lipoprotein (LDL) oxidation lag time and atherosclerotic lesion formation in Watanabe heritable hyperlipidemic (WHHL) rabbits. Thirty-one, 3-month-old WHHL rabbits were divided into three experimental groups. One group (n=10) was fed standard rabbit feed alone and served as a control, a second group (n=11) was supplied with the same feed containing 500 mg alpha-tocopherol/kg and a third group (n=10) was given a feed containing 100 mg astaxanthin/kg. Plasma lipids, lipoproteins and LDL oxidation lag time were followed for 24 weeks. At the end of the treatment period, the animals were killed and the thoracic aorta was used for evaluation of the degree of atherosclerosis. Colour photographs of the intimal surface of the vessel were taken for determination of the atherosclerotic area. Cross-sections of the thoracic aorta were used for histological examination and for determination of intimal thickening. Specimens of the vessel were used for determination of the tissue cholesterol content. Plasma cholesterol remained at a high level during the time of the experiment and there were no differences between the experimental groups. After 24 weeks, the LDL oxidation lag time was 53.7+/-1.7 min, 109+/-4 min (P<0.001) and 56.4+/-3.4 min (P=0.47) in the control, alpha-tocopherol and astaxanthin groups, respectively. In the thoracic aorta, the atherosclerotic area was 80.7+/-5.1%, 67.1+/-6.7% (P=0.13) and 75.2+/-5.7% (P=0.49) in the control, alpha-tocopherol and astaxanthin groups, respectively. The intimal thickening was 45.6+/-3.2%, 44.0+/-4.1% (P=0.89) and 40.0+/-4.5% (P=0.33) in the control, alpha-tocopherol and astaxanthin groups, respectively. Finally, the cholesterol content was 107+/-9 mol/g, 95.7+/-11.5 mol/g (P=0.31) and 101+/-5 mol/g (P=0.33) in the control, alpha-tocopherol and astaxanthin groups, respectively. It can be concluded that alpha-tocopherol but not astaxanthin prolonged the LDL oxidation lag time. The two antioxidative substances did not prevent atherogenesis in WHHL rabbits in this setting.
authors.affiliation: Department of Pharmacology, Faculty of Health Sciences, Linköping University, Linköping SE-581 85, Sweden. leif.jacobsson@imv.liu.se
authors.forename: Leif S
authors.initials: LS
authors.lastname: Jacobsson
authors.forename: Xi Ming
authors.initials: XM
authors.lastname: Yuan
authors.forename: Bo
authors.initials: B
authors.lastname: Ziedén
authors.forename: Anders G
authors.initials: AG
authors.lastname: Olsson
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000473:pathology*; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D005260:Female; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy / Q000473:pathology; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011336:Probability; D011817:Rabbits; D012016:Reference Values; D012680:Sensitivity and Specificity; D024341:Xanthophylls; D024502:alpha-Tocopherol / Q000494:pharmacology*; D019207:beta Carotene / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D008077:Lipoproteins, LDL; D024341:Xanthophylls; D019207:beta Carotene; C005948:astaxanthine; D024502:alpha-Tocopherol