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題 名 | 以動物模式評估比較硃砂單方及含硃砂之複方中藥對於肝臟和腎臟毒性損傷與安全性研究=Studies of Toxicological Effects and Safe Evaluation of Liver and Kidney by the Single and Compound Cinnabar Used in In Vivo System |
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編 次 | (2-1) |
作 者 | 黃俊發; 蘇奕彰; 陳雅雯; 吳錦景; | 書刊名 | 中醫藥年報 |
卷 期 | 3 2014.12[民103.12] |
頁 次 | 頁(67)1-(67)39 |
分類號 | 414.5 |
關鍵詞 | 硃砂單方; 肝臟; 腎臟; 毒性反應; 安全劑量; 使用期限; Single cinnabar; Liver; Kidney; Toxicological effects; Safe dosage; Regimen period; |
語 文 | 中文(Chinese) |
中文摘要 | 本研究計畫之目的為:探求在硃砂使用下,是否會引起肝、腎組織毒性反應?並且以肝腎毒性損傷為指標來進一步了解:硃砂在先前研究結果所推估具鎮靜安神作用之硃砂使用安全劑量與期程內對肝腎毒性是否尚未產生? 首先,以感應耦合電漿質譜儀 (ICP-MS)來分析所購得不同之市售水飛硃砂所含汞與其他金屬含量的差異。接續,在給予實驗動物 (雄性鼷鼠 )餵食硃砂單方 (10 and 100 mg/kg)、及氯化汞 (HgCl2-0.2 mg/kg, 為已知之毒性無機汞化物,作為正向控制組 )不同時間後,將鼷鼠犧牲,分析血液、肝臟及腎臟中汞金屬濃變化,以便能分析硃砂單方經腸胃吸收後在肝、腎組織分佈的情形;並且分析實驗鼷鼠:肝、腎功能指標 (血漿生化值-GOT, GPT, LDH, BUN, Creatinine的變化、尿液中蛋白含量 (Urine protein)、 Creatinine之改變)、肝、腎組織顯微構造改變 (組織病理檢查實驗 )、以及與肝臟、腎臟毒性損傷相關指標 (脂質過氧化 (LPO)產生、穀胱甘肽 (GSH)變化、與細胞組織毒性傷害有關之重要傳訊核醣核酸 (mRNA))變化情形。 由分析市售水飛硃砂樣品發現:不同來源 (或是製備過程不同 )之水飛硃砂,其中汞金屬含量亦有所差異,同時也含有其他重金屬的存在 (像是:鋁 (Al)、鎂(Mg)、鉛(Pb)、硒(Se)、鋅(Zn)、鋇(Ba)等)。經由綜合分析比較後發現市售水飛硃砂 -III所含之毒性重金屬(鋁、鉛、鋅 )較低,因此選擇市售水飛硃砂 -III來進行動物實驗用。給予實驗動物 (鼷鼠)連續餵食較高劑量硃砂單方 (100 mg/kg)與氯化汞 (HgCl2-0.2 mg/kg)2週後,即引起肝腎功能損傷、汞金屬大量的蓄積於肝腎組織中、肝腎組織結構破壞、相關毒性損傷指標改變 (包含:脂質過氧化產生、穀胱甘肽減少 (耗損)、與細胞組織毒性傷害有關之重要傳訊核醣核酸改變( Kim-1, HO-1, Caspase-3, GPx)),且氯化汞組的反應程度比較高劑量硃砂單方 (100 mg/kg)組要高出許多。而低劑量硃砂單方 (10 mg/kg,為本草綱目所建議硃砂使用治療劑量之範圍內 )在連續餵食 2週後,即引起腎臟損傷 (尿液中蛋白含量增加、脂質過氧化產生、 Kim-1, Caspase-3, GPx 等與毒性傷害有關之傳訊核醣核酸改變、組織構造異常、並伴隨著明顯汞金屬蓄積於組織中 ),而肝臟組織的傷害則是在連續餵食 4週後才觀察到。 綜合本研究計畫之實驗結果與先前得之研究結果,所獲得初步結論為:(1)對於市售(水飛)硃砂的使用,須嚴格管控硃砂的製程與產品品質;(2)在較長時間 (> 2週)給於實驗動物暴露低劑量 (10 mg/kg)硃砂單方,仍會造成肝腎毒性傷害,且腎臟組織對於硃砂之毒性損傷反應較肝臟組織敏感;(3)推估人類使用硃砂之安全劑量為:0.05~0.07 g/day,連續使用不可超過 14天。 |
英文摘要 | The aim of this research project was to investigate the toxic effects, initiation time, and possible mechanisms of cinnabar-induced in liver and kidney of mice and to estimate the detailed information for the safe dosage and regimen period of cinnabar. In this project, we first used ICP-Mass to analysis mercury and other metals contents of three commercial cinnabar samples. The results showed that one (the commercial cinnabar-I) of them had much lower Hg levels (< 60 %) and contaminated with other toxic metals (such as: Al, Ba, Mg, Pb, Se…ect.). The other two (the commercial cinnabar-II and -III) of them had better quality. Thus, the commercial cinnabar-III was used throughout the experiments. After oral administration with single cinnabar (10 and 100 mg/kg) or HgCl2 (0.2 mg/kg, the positive control) for different time intervals (2-12 weeks), the results showed that it could cause the impairment of liver and kidney functions (including: GOT, GPO, LDH, BUN, creatinine, and urine protein and urine creatinine), significant mercury accumulation, destroy tissue structure, and change in the related biomarkers of toxic injuries (including: LPO production, GSH depletion, alteration the mRNA expression of toxicological effects) in liver and kidney after oral administration with 100 mg/kg cinnabar or 0.2 mg/kg HgCl2 for 2 consecutive weeks (14 days), which the efficacy of 0.2 mg/kg HgCl2 was more than 100 mg/kg cinnabar. Furthermore, oral exposed of ICR mice to low-dose cinnabar (10 mg/kg/day, which was the dosage of clinical used in TCM) for 2 consecutive weeks (14 days) was induced kidney dysfunction, including: increase in urine protein, tissue LPO production, abnormalities of tissue structure and toxic damage mRNA (Kim-1, HO-1, Caspase-3, and GPx) expressions, which accompanied with marked Hg accumulation; and liver injuries were observed after exposed to low-dose cinnabar (10 mg/kg) for 4 consecutive weeks. Thus, these results provide the important evidence that long-tern (> 2 weeks) exposure to low-dose cinnabar can induce oxidative stress damage causing cell death and tissue injuries in kidney and liver. Beside on these results and previous findings (the non-observable neurotoxic effects dose of cinnabar), it can help us to calculate the safe dosage and regimen period of cinnabar, accurately. |
本系統中英文摘要資訊取自各篇刊載內容。