瑪黛茶對大鼠肝臟代謝乙醯胺酚之影響

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題名:	瑪黛茶對大鼠肝臟代謝乙醯胺酚之影響 Effect of Mate Tea on the Metabolism of Acetaminophen in Rats Livers
作者:	劉昀達;Yun-Ta Liu
貢獻者:	營養學系碩士班
關鍵詞:	瑪黛茶;乙醯胺酚;抗氧化;肝毒性;大鼠;Mate tea;acetaminophen;antioxidant;hepatotoxicity;rats
日期:	2013-07-30
上傳時間:	2013-10-15 13:33:49 (UTC+8)
出版者:	中國醫藥大學
摘要:	瑪黛茶是南美洲盛行的傳統飲料，許多研究證實瑪黛茶具有抗發炎、抗氧化、抗乳癌與結腸癌等功效，但瑪黛茶對於肝臟藥物代謝酵素的影響仍不清楚。本研究將探討瑪黛茶成分含量、自由基捕捉能力與其對大鼠肝臟乙醯胺酚(Acetaminophen, APAP)代謝之影響。本研究分兩部分，實驗一分析市售七種原味瑪黛茶之50% (v/v)乙醇萃出物(Mate tea extract, MTE)的植化素組成與含量、自由基清除能力與cytochrome P450 3A之抑制作用；結果顯示總酚量與總咖啡?衍生物的含量對於1,1-diphenyl-2-picrylhydrazyl (DPPH)和2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS)自由基清除能力有著顯著的正相關性(r > 0.7)。體外實驗結果顯示瑪黛茶萃出物會抑制大鼠CYP3A (IC50 = 132.2 μg/mL)與人類CYP3A4 (IC50 = 210.0 μg/mL)之活性，進一步實驗判定為競爭型抑制作用。實驗二以雄性SD大鼠評估瑪黛茶對APAP代謝之影響，大鼠分別食用含有1.5%與3%瑪黛茶葉粉末(Mate tea leaves, MTL)之飼料兩週，隔夜禁食後腹腔注射APAP (1000 mg/kg b.w.)，部分大鼠放入代謝籠中收取尿液，12小時後犧牲，取其血漿和肝臟測定肝腎功能指標與APAP及其代謝物濃度與藥物代謝酵素活性；結果發現APAP明顯提高肝損傷指標aspartate transaminase (AST)和lactate dehydrogenase (LDH)，而食用3%瑪黛茶葉粉末之大鼠再給予注射APAP後會更明顯增加APAP的肝損傷。此外，攝食含瑪黛茶葉粉末之大鼠血漿、肝臟及尿液中APAP-GSH濃度皆會明顯增加，肝臟中CYP3A和CYP1A2活性亦有顯著上升。值的注意的是，攝食瑪黛茶葉粉末飲食會提高肝臟中APAP protein adduct含量。由以上結果顯示瑪黛茶具有抗氧化活性，但卻會增加大鼠肝臟中APAP經由CYP代謝而對肝臟造成損傷。 Objectives: Due to occupational exposure to radiation, the risk of radiation-associated diseases among radiological technologists was concerned. Despite the expertise in radioprotection, radiological Mate tea is a popular traditional breverage in South America. Many studies indicated that mate tea had anti-inflammatory, antioxidant, anti-breast and anti-colon cancer activities. However, the effect of mate tea on hepatic drug-metabolizing enzymes is still not clear. To investigate the components in mate tea, and their free radical scavenging ability and effect of mate tea on the metabolism of acetaminophen (APAP) in rat livers, two experiments were conducted. Experiment I: This study is to identify the composition and concentration of phytochemicals in 50% (v/v) ethanol extract of mate tea, and evaluate their free radical scavenging ability and cytochrome P450 3A inhibitory effect. Results show that total phenol content and some caffeoyl derivates had significantly higher correlation (r > 0.7) to the free radical scavenging ability against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radicals. Mate tea extract showed significantly and competitively inhibition on CYP3A (IC50 = 132.2 μg/mL) and CYP3A4 (IC50 = 210.0 μg/mL) activities in rat and human liver microsome, repectively. Experiment II: To evaluate the effect on APAP metabolism, male Sprague-Dawley rats were fed a diet containing 1.5% or 3% mate tea leaves (MTL) for two weeks. Afte fasting over night, APAP was administered i.p. at 1000 mg/kg b.w., and sacrificed 12 hrs later. The plasma and liver are used for measuring hepatic and renal fuction index, the concentrations of APAP and its metabolites and the activities of drug-metabolizing enzyme. Results show that rats treated with APAP significantly increased aspartate transaminase and lactate dehydrogenase, and 3% MTL feeding significantly increased the hepatotoxicity of APAP. In addition, the concentrations of APAP-GSH in plasma, liver and urine in MTL treated rats were increased, and the activities of CYP3A and CYP1A2 in liver were also elevated. It was noted worthy that APAP protein adduct was induced by MTL. In conclusion, mate tea may exert antioxidant ability, but it may also enhance APAP-induced liver damage by increasing CYP 3A and 1A2 activities and CYP-mediated APAP metabolism in rat liver.
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