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標題: | 全氟碳化物對雄鼠之毒性及其藥物動力學研究 Pharmacokinetics and toxicity of perfluorinated chemicals in male rats |
作者: | Chen-Che Su 蘇陳則 |
指導教授: | 蔡懷楨(Huai-Jen Tsai) |
關鍵字: | 全氟碳化物,藥物動力學,液相層析串聯質譜儀,線上固相萃取, Perfluorinated chemicals,pharmacokinetics,Liquid chromatography tandem mass spectrometry,On-line solid-phase extraction, |
出版年 : | 2013 |
學位: | 碩士 |
摘要: | 全氟碳化物是一群被廣泛應用於工業界的人工合成的穩定化學物質,並且被認為是內分泌的干擾因子,正因為如此才受到大家的關注。但有關於全氟碳化物中的PFUA、PFDoA、PFDS和PFBA毒性資料相當稀少,因此本研究的目標在於對PFUA、PFDoA、PFDS和PFBA等全氟碳化物做初步的毒理試驗並研究其藥物動力學。雄性SD大鼠(N=4)經單一胃管餵食暴露不同劑量,分別為0、0.5和 5 mg/kg。接下來收集88天的血液及尿液樣本並利用新開發的線上固相萃取液相層析串聯質譜儀(LC-MS/MS)方法進行分析。這些資料將被用來建構藥物動力學參數。大鼠血清中的雌激素、黃體素、睪固酮、膽固醇、LH、FSH則利用市售的ELISA試劑進行檢驗。PFUA和PFDoA在尿液中皆無法被偵測到。PFUA和PFBA的藥物動力學參數並沒有顯著差異,顯示在雄性大鼠中0.5到5 mg/kg之間的劑量呈現線性的藥物動力學,然而PFDoA則否,呈現非線性的藥物動力學。PFUA在高暴露組(5 mg/kg)發現雌激素顯著增加而黃體素顯著降低。PFDS睪固酮顯著降低,PFBA則呈現雌激素顯著下降,顯示PFUA、PFDS及PFBA可能會影響固醇類激素的生合成。這些結果顯露了PFUA、PFDS和PFBA為環境內分泌干擾物,值得我們更進一步研究全氟碳化物對人類健康影響的機制。 Perfluorinated chemicals (PFCs), considered as endocrines disrupters and widely used in industries, are a group of stable man-made organic compounds. The potential health effects caused by PFCs exposures have been of great concerns. However, there is no toxicity-related study on PFUA, PFDoA, PFDS, and PFBA. Therefore, this study was aimed to study pharmacokinetics and preliminary toxicity test for PFUA, PFDoA, PFDS, and PFBA. Male SD rats (n=4) were treated with a single dose of PFUA by oral gavage at 0, 0.5 and 5 mg/kg. Subsequently, urine and serum samples were collected for 88 days and analyzed with a newly-developed on-line solid-phase extraction liquid chromatography tandem mass spectrometry (LC-MS/MS) method. These data were fit with pharmacokinetic models with the Win-Nonlin software. Concentration of serum estradiol, progesterone, testosterone, cholesterol, FSH and LH were measured by ELISA using commercial rat ELISA kits. PFUA and PFDoA were not detectable in urine. No significant differences were observed in PFUA and PFBA in pharmacokinetic parameters at 0.5 and 5 mg/kg to suggest linear pharmacokinetics. However, PFDoA presented non-linear pharmacokinetics. PFUA at the highest dose caused significant increase in serum estradiol levels but decrease in serum progesterone levels. PFDS at the highest dose caused significant decrease in serum testosterone levels. PFBA at the highest dose decrease in serum estradiol levels, implying that PFUA, PFDS and PFBA may affect steroidogenic hormone biosynthesis of male SD rats. These results first reveal that PFUA, PFDS and PFBA are environment endocrine disrupters and deserve further studies on its potential effects on human health. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17724 |
全文授權: | 未授權 |
顯示於系所單位: | 分子與細胞生物學研究所 |
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