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標題: | 奈米粒子MIL-101(Cr)之急性毒性測試及重複毒性測試 Acute oral toxicity and repeated dose 28-day oral toxicity studies of MIL-101(Cr) nanoparticles |
作者: | Chia-Hung Liu 劉家宏 |
指導教授: | 劉興華 |
關鍵字: | MIL-101(Cr) 奈米粒子,微核試驗,急性毒性試驗,連續28日毒性試驗, MIL-101(Cr)NPs,micronucleus assay,acute toxicity study,repeated dose 28-day oral toxicity study, |
出版年 : | 2019 |
學位: | 博士 |
摘要: | 奈米科技倍被認為被認為是一種操縱奈米級物質的新興技術。奈米粒子定義為大小介於1到100奈米的顆粒物質。最近出現的金屬有機骨架材料吸引了很多研究者的興趣。在各種金屬有機骨架材料中,MIL-101(Cr) 奈米粒子是最具代表性的金屬有機骨架材料之一。MIL-101(Cr) 奈米粒子的獨特性質使其成為工業上的理想選擇,例如藥物輸送系統。然而,重要的毒性問題也隨著這些有前景的應用而浮出檯面,特別是在生物醫學領域。目前MIL-101(Cr) 奈米粒子的毒性尚未清楚。本論文將MIL-101 (Cr) 奈米粒子口服給予ICR小鼠以評估其短期和長期體內毒性。首先,微核試驗的結果顯示MIL-101 (Cr) 奈米粒子可能誘導染色體結構結構及數目上的缺失,導致紅血球生成缺陷。在急性毒性試驗,組間體重增加、食物和水的消耗量和相對器官重量之結果相似,而臨床生化檢驗結果的變化則沒有劑量相關性。在連續28日經口毒性試驗,組間體重增加、食物和水的消耗量和血液學分析之結果相似,而相對器官重量的變化則沒有劑量相關性。臨床生化檢驗方面,在母鼠的1000 mg/kg 組別中,其GOT和總膽紅素上升、白蛋白/球蛋白比值下降,但無特異性及劑量關係。接著對肝臟切片進行組織化學染色發現在對照組或者高劑量組之肝臟,腎臟,心臟,脾臟, 腎上腺,副睪丸,睪丸,子宮及卵巢中,兩者皆無明顯的變化 Nanotechnology has considered an emerging technology that refers to the manipulation of matter at nanoscale. Nanoparticles (NPs) are defined as particulate substances with a size in the range of 1 to 100 nm. The recent emergence of porous metal-organic frameworks (MOFs) has attracted a great deal of research interest. Among all kinds of MOFs, MIL-101(MIL, Material of Institut Lavoisier) (Cr)NPs is one of the most representative MOFs. The unique properties make MIL-101(Cr)NPs an excellent candidate for industrial applications, for examples drug delivery systems. However, important toxicological concerns arose from these promising applications, notably in biomedicine. The toxicity of MIL-101(Cr)NPs has never been reported so far. In this study, the specific aim was to determine the effect of MIL-101(Cr)NPs orally administered to ICR mice by evaluating the short-term and long-term in vivo toxicity. First, by micronucleus assay, we demonstrated that MIL-101(Cr)NPs might induce structural or numerical chromosomal damage, which result in defeat erythropoiesis. In acute toxicity study, body weight gain, food or water consumption and relative organ weight were similar between groups. The changes in clinical chemistry showed no dose correlation. In repeated dose 28-day oral toxicity study, body weight gain, food or water consumption and hematology analysis were similar between groups. The changes in relative organ weight were not dose correlated. Increases in GOT and total bilirubin and decreases in albumin/globin ratio were observed in females of 1000 mg/kg group. The results indicated non-specific finding and without dose- related relationship . Next, we performed a histochemical staining in the sections of liver. The results showed that no treatment-related histopathological changes were recorded in the liver, kidney, heart, spleen, adrenal gland, epididymis, testis, uterus, and ovary of the control mice or high-dose (1000 mg/kg) MIL-101(Cr)NPs. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/74890 |
DOI: | 10.6342/NTU201904194 |
全文授權: | 有償授權 |
顯示於系所單位: | 毒理學研究所 |
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