Trans Fatty Acids - Culprits of Alzheimer''s Disease and Its Prevention / 反式脂肪酸與阿茲海默症之相關性及其預防

博士 / 國立臺灣大學 / 食品科技研究所 / 100 / Trans fatty acids (TFA) are unsaturated fatty acids with at least one double bond in the trans-configuration. Some studies have shown that TFA are not only obtained exogenously from food intake, but also generated endogenously by free radicals. Alzheimer’s disease (AD) is a progressive and neurodegenerative disease. Oxidative stress induced by beta-amyloid peptide (Aβ) was considered as a critical component in the pathogenesis of AD. The aim of this study was to investigate the correlation between TFA and AD. In photochemical reaction assay, trans arachidonic acids (TAA) could be effectively generated by thiyl-radicals induced by UV-irradiation of 2-mercaptoethanol (2-ME). Myricetin, luteolin and quercetin had the highest activities in preventing thiyl radical-induced TAA formation, whereas sesamol, gallic acid and vitamins had the lowest. The structures of flavonoids with higher thiyl radical scavenging activities were a 3’, 4’-dihydroxyl group in the B ring and a 2,3-double bond combined with a 4-keto group in the C ring. In the PC-12 cell study, TFA levels in the cells showed a marked increase after treatment with 2-ME and H2O2. The results showed that the elevation of TFAs in PC-12 cells induced by H2O2 and 2-ME could be reduced by quercetin, curcumin, resveratrol, retinol acetate, α-tocopherol and ascorbic acid in both pretreatment and cotreatment experiments. Among the test antioxidants, retinol acetate exhibited the highest activities on reducing TFA formation in PC-12 cells. In addition, we also found that quercetin could enhance the activity of retinol acetate on reducing TFA formation in the cotreatment experiment. In dextran sodium sulfate (DSS)-induced inflammatory bowel disease model and azoxymethane (AOM)-induced colon carcinogenesis model, the results showed that TFA levels in mice colon mucosa did not increase by DSS or AOM treatments. In Senescence-accelerated prone mouse 8 (SAMP8) model, TFA levels in hearts, spleens, lungs, brains and hippocampuses of 12-month-old SAMP8 mice were higher than 12-month-old SAMR1 mice. The elevation of TFA levels might be resulted from the accumulation of free radical stress during pathogenesis of AD and aging. Finally in human amyloid protein precursor (hAPP) transgenic mice model, we found TFA levels in hearts, kidneys, and blood cells of six-month-old J20 mice were significantly higher than six-month-old B6 mice. The elevation of TFA levels might be resulted from the accumulation of free radical stress during pathogenesis of AD.

Identiferoai:union.ndltd.org:TW/100NTU05252031
Date January 2012
CreatorsWei-Lun Hung, 洪偉倫
Contributors何其儻
Source SetsNational Digital Library of Theses and Dissertations in Taiwan
Languagezh-TW
Detected LanguageEnglish
Type學位論文 ; thesis
Format249

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