https://scholars.lib.ntu.edu.tw/handle/123456789/111207
標題: | 監測活體內丙烯醯胺之代謝物指紋 In vivo Monitoring Metabolite profiles of Acrylamide |
作者: | 羅宇軒 Luo, Yu-Syuan |
關鍵字: | 丙烯醯胺;谷胱甘?毒物代謝體學;液相層析-三段四極柱質譜儀;微透析活體採樣;Acrylamide;Glutathione;Metabonomics;LC-MS/MS;In vivo microdialysis | 公開日期: | 2012 | 摘要: | 丙烯醯胺(acrylamide)的潛在致癌性及廣泛地存在於高溫炒炸食品中,近年來對於丙烯醯胺的食品安全議題日益受到重視。研究指出,丙烯醯胺的潛在致癌性質主要來自於中間代謝物環氧丙醯胺(glycidamide),而丙烯醯胺及環氧丙醯胺會與體內的谷胱甘肽(glutathione)結合而去除毒性。本研究旨在建立體內微透析液相層析串聯是質譜儀方法同時分析Sprague-Dawley大鼠體內血中丙烯醯胺Phase I & II reactions所有代謝物:丙烯醯胺(AA)、環氧丙醯胺(GA)、環氧丙醯胺之水解產物2,3-羥基丙醯胺(glyceramide)及丙烯醯胺和環氧丙醯胺與谷胱甘肽的共價鍵結物(AA-GSH & GA-GSH)。這些結果可供給研究物種間代謝機制差異,以評估丙烯醯胺對於人體的致癌性。本研究經由腹腔注射法,麻醉後分別給予大鼠0.1 mg/kg及5 mg/kg的丙烯醯胺,藉微透析活體採樣技術,串連液相層析-三段四極柱質譜儀,並佐以管柱交替(column-switching)法即時定量丙烯醯胺代謝物隨時間的變化。在0.1 mg/kg 劑量下,AA及AA-GSH 的代謝反應速率常數分別為 0.26 及 0.23 hr-1;半衰期則分別為2.67及2.97 小時。在5 mg/kg 劑量下,AA、GA及AA-GSH的代謝反應速率常數分別為0.23、0.14及0.20 hr-1;半衰期則分別為2.97、4.90及3.52 小時。原型物AA、代謝後GA及AA-GSH各自分別占總劑量的86.1%、8% 及1%。本研究結果指出,腹腔注射下,SD大鼠血中之AA代謝主要以從AA到GA為主。 Acrylamide is a potential human carcinogen and widely existed in high temperature processed foods. As a result, the long-term exposure of acrylamide on food safety issue has been concerned. Previous studies suggested that metabolic activation of acrylamide to glycidamide might be responsible for its genotoxicity. Meanwhile, acrylamide and glycidamide would be detoxified by glutathione transferase to acrylamide- and glycidamide-glutathione adducts, and glycidamide can be spontaneously hydrolyzed or detoxified by epoxide hydrolase to glyceramide. This study is aimed to reveal acrylamide metabonomics in blood of Sprague-Dawley rats, including acrylamide, glycidamide, glyceramide, acrylamide-glutathione adducts (AA-GSH), glycidamide-glutathione adducts(GA-GSH), with an automated in vivo microdialysis isotope-dilution solid-phase extraction LC-MS/MS method. Results from this study can provide critical quantitative information of acrylamide metabolism in SD rats. Anaesthetized rats were treated with acrylamide of 0.1mg/kg and 5mg/kg by I.P. injection, respectively. Real-time acrylamide metabolites were profiled with an automated isotope-dilution column-switching LC-MS/MS method. The elimination rate constant (ke) was 0.26 hr-1 for AA and 0.23 hr-1 for AA-GSH and the half life (T1/2) was 2.67 hr for AA and 2.97 hr for AA-GSH in rats treated with 0.1 mg/kg. Ke of AA, AA-GSH and GA were 0.23, 0.2 and 0.14 hr-1, and T1/2 were 2.97, 3.52 and 4.9 hr for AA, AA-GSH and GA in rats treated with 5 mg/kg, respectively. Estimated with their area under curve (AUC), the AA, GA and AA-GSH account for 86.1%, 8% and 1% , respectively. This study reveals that the majority of absorbed AA is metabolically activated to GA. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/257805 |
顯示於: | 環境與職業健康科學研究所 |
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