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Title: Changes in Pathology and iron regulation in Guinea Pigs in relation to the lipid content of the diet
Authors: YE PENG
Keywords: guinea pig, non-alcoholic fatty liver disease, cholesterol, atherosclerosis, iron metabolism, lipid peroxidation
Issue Date: 21-Aug-2012
Source: YE PENG (2012-08-21). Changes in Pathology and iron regulation in Guinea Pigs in relation to the lipid content of the diet. ScholarBank@NUS Repository.
Abstract: Studies have revealed that elevated levels of iron promote the formation of atherosclerotic plaques and may contribute to the disease progression, while zinc was found to have a beneficial effect in rabbits. Guinea pigs have been suggested to be a realistic animal model for studying atherosclerosis, as their plasma lipoprotein profile closely mimics that of humans. This study initially attempted to further investigate the changes in iron and zinc levels in the atherosclerotic plaque, elemental and biochemical changes in the intima during initiation and progression of atherosclerosis over time and cause-consequence relationship between oxidative stress and atherosclerosis. For that purpose, male guinea pigs were fed a moderate cholesterol (10% fat, 0.17% cholesterol) or high cholesterol diet (10% fat, 0.33% cholesterol) alongside controls (4% fat, no cholesterol) for 2, 4, or 6 months. We found that dietary cholesterol significantly raised the cholesterol concentrations in plasma and liver. Plasma and liver cholesterol oxidation products (24-OH cholesterol, 7a-OH cholesterol, 7?-OH cholesterol and 7-ketocholesterol) were also elevated in cholesterol-fed groups. However, there was no significant change in plasma and liver lathosterol, F2-isoprostanes or arachidonic acid levels. Unfortunately the diets failed to significantly alter atherosclerotic burden in the animals although iron/zinc concentrations within the few lesions (possibly early plaques) observed were suggestive of early atherosclerotic plaque formation and consistent with previous data. It may be that previous work on cholesterol-induced atherosclerosis in the guinea pig model in the literature could be questionable. On the other hand, significant liver damage and indications of advanced fatty liver disease were observed, together with decreased plasma hepcidin and transferrin levels in cholesterol-fed groups. Liver iron and cholesterol were shown to be increased in cholesterol-fed groups and a high correlation between them was observed. Plasma iron levels were shown to be increased, probably due to decreased plasma hepcidin. No significant difference was shown in liver ferritin, transferrin receptor-2 levels and heme oxygenase-1 activities between the three dietary groups. Liver hemosiderin depositions were found in cholesterol-fed groups but not in control group, which, together with almost normal oxidative stress levels, suggests that the excess iron was safely sequestered in hemosiderin. Thirdly, spleen enlargement was also found in cholesterol-fed groups, which could be explained by possible portal vein hypertension, consistent with the findings of increased liver collagen levels in those animals. There was a continuous rise in spleen iron with age in all groups, but no significant difference in spleen total iron levels was found between the groups. Spleen heme levels significantly decreased in high cholesterol group. However, spleen hemosiderin deposition was seen in all groups and no significant difference was found between them.
Appears in Collections:Ph.D Theses (Open)

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