(3.236.214.19) 您好!臺灣時間:2021/05/10 08:07
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:黃致云
研究生(外文):Zhi-Yun Huang
論文名稱:人參及人參皂苷Rg1與N-乙醯半胱胺酸在順氯氨鉑引發的腎毒性於純系小鼠的藥效評估
論文名稱(外文):Effects of ginseng , ginsenoside Rg1 and N-acetylcysteine on cisplatin-induced nephrotoxicity in inbred mice
指導教授:陳世銘陳世銘引用關係
學位類別:碩士
校院名稱:臺北醫學大學
系所名稱:藥學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
語文別:中文
論文頁數:98
中文關鍵詞:Cisplatin腎毒性人參人參皂苷N-乙醯半胱胺酸甲型腫瘍壞死因子p21增殖細胞核抗原
外文關鍵詞:Cisplatin nephrotoxicityginsengginsenosidesN-acetylcysteineTNF-alphap21PCNA
相關次數:
  • 被引用被引用:1
  • 點閱點閱:165
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:1
順氯氨鉑(cisplatin, CDDP)是臨床上治療固體癌的常用化學治療藥物,其所引起的腎毒性常是限制臨床使用的主要原因。本研究的目的即在於評估人參及其純成分人參皂苷與N-乙醯半胱胺酸(N-acetylcysteine)作為預防藥物於CDDP所引起的腎炎之預防效果。實驗以6週齡雌鼠(BALB/c mice, female),經腹腔連續五天給予CDDP 5 mg/kg/d以引發CDDP腎炎。在給予CDDP前五天開始經口單獨投予小鼠人參濃縮劑(ginseng extract,GE) 250 mg/kg/d或人參皂苷(ginsengoside,GS) Rg1 5 mg/kg/d及並分別合併N-acetylcysteine 450 mg/kg/d作為預防藥物。實驗結果顯示,給予GE、GS Rg1及N-acetylcysteine對於N-acetyl-beta-D-glucosaminidase (NAG) 、尿中肌酸酐(urine creatinine)、尿蛋白(urine protein)與血中尿素氮(BUN)皆有不同程度的改善效果;腎組織損傷相較於對照組也有減緩的趨勢。在免疫螢光染色方面,TNF-alpha(tumor necrosis factor-alpha)的量明顯受到抑制,p21及PCNA(proliferating cell nuclear antigen)的表現亦有不同程度的增加。綜合實驗結果,合併治療組對於預防CDDP所引起的腎毒性效果最佳。因此可以推論,經口投予人參濃縮劑、人參皂苷Rg1、N-acetylcysteine可以藉由抑制發炎反應、阻止細胞週期的前進並促進DNA修復以達到腎臟保護的效果。
Cisplatin (CDDP) is one of the most commonly used antineoplastic agents for the solid tumor treatment. The major side effect of CDDP is nephrotoxicity. It is dose-related and has become a chief limitation of its clinical use. The purpose of this study was to evaluate the preventive effects of ginseng extract (GE), its active component, ginsenoside Rg1(GS Rg1) and N-acetylcysteine (NAC) on CDDP-induced nephrotoxicity in bred mice. Six-week-old female BALB/c mice were administered with 5 mg/kg of CDDP intraperitoneally once daily for 5 days. 250 mg/kg of GE or 5 mg/kg of GS Rg1 combination with 450 mg/kg/d of NAC were given orally once a day from 5 days before CDDP administration. Urinary N-acetyl-??-D-glucosaminidase (NAG), urinary creatinine(Ucr) and blood urea nitrogen (BUN) were determined, Renal tissues were served to histological examination. The antibodies including tumor necrosis factor-alpha(TNF-alpha), p21 and proliferating cell nuclear antigen (PCNA) was chosen to recognize the specific antigens that deposited in injury sites. Our findings demonstrated that GE, GS Rg1 and NAC attenuate CDDP-induced nephrotixicity by inhibiting TNF-alpha expression and inducing cell cycle arrest to repair DNA damage.According to this study, the effect of combination treatment was superior to other group.
目錄 I
圖目錄 V
表目錄 VII
縮寫表 i
中文摘要 ii
空Abstract iv
第一章 緒言 1
第二章 文獻回顧 4
第一節 順氯氨鉑(Cisplatin)的作用機轉及臨床使用 4
第二節 Cisplatin引起腎毒性的臨床表徵與機轉 10
第三節 Cisplatin與細胞週期的調控 17
第四節 人參及其藥效研究 25
4.1 生藥學的考察 25
4.2 人參的藥效研究 27
第五節 人參皂苷Rg1之藥效研究 31
5.1 人參皂苷之結構特性 31
5.2人參皂苷Rg1之藥效研究 34
第六節 N-乙醯半胱胺酸 N-acetylcysteine 36
第三章 研究目的 39
第四章 材料與方法 40
第一節 人參濃縮劑與N-乙醯半胱胺酸在CDDP引起腎炎模型的藥效評估 40
1.1實驗動物 40
1.2實驗藥物 40
1.3人參濃縮劑與N-乙醯半胱胺酸在此腎炎模型之實驗設計 41
1.4尿液收集 41
1.5動物犧牲法、血液及組織切片製作 41
1.6尿中NAG、Creatinine及蛋白的含量分析 42
1.7血清中BUN值的含量測定 43
1.8 Periodoic acid-Schiff’s(PAS)stain組織染色 43
1.9組織損傷程度的量化 44
1.10免疫螢光染色(Immunofluorescence) 44
1.11統計方法 45
第二節 人參皂苷Rg1與N-乙醯半胱胺酸在CDDP引起腎炎模型的藥效評估 47
2.1實驗動物 47
2.2實驗藥物 47
2.3人參皂苷合併N-乙醯半胱胺酸在此腎炎模型之實驗設計 47
2.4尿液收集 48
2.5動物犧牲法、血液及組織切片製作 48
2.6尿中NAG、Creatinine及蛋白的含量分析 48
2.7血清中BUN值的含量測定 48
2.8 Periodoic acid-Schiff’s(PAS) stain組織染色 48
2.9組織損傷程度的量化 48
2.10免疫螢光染色 48
2.11統計方法 48
第五章 結果 50
第一節 人參濃縮劑與N-乙醯半胱胺酸在CDDP引起腎炎模型的藥效評估 50
1.1 尿中NAG、Creatinine及蛋白的含量分析 50
1.2 血清中BUN分析 51
1.3 組織病理PAS染色 51
1.4組織損傷量化分析 52
1.5免疫螢光染色 52
第二節 人參皂苷Rg1及N-乙醯半胱胺酸在CDDP引起腎炎模型的藥效評估 62
2.1 尿中NAG、Creatinine及蛋白的含量分析 62
2.2 血清中BUN分析 63
2.3 組織病理PAS染色 63
2.4組織損傷量化分析 64
2.5免疫螢光染色 64
第六章 討論 74
第一節 人參濃縮劑及人參皂苷Rg1在CDDP引起腎炎模型的藥效評估空. 74
第二節 N-乙醯半胱胺酸在CDDP引起腎炎模型的藥效評估 78
第三節 人參濃縮劑及人參皂苷Rg1合併N-乙醯半胱胺酸在CDDP引起腎炎模型的藥效評估 81
第七章 結論 84
參考文獻 86
中華民國衛生署. 中華民國九十五年臺灣地區死因統計結果摘要 http://www.doh.gov.tw/statistic/index.htm. Accessed June 11th, 2007.
2.世界衛生組織. Cancer: diet and physical activity''s impact. Accessed May 28th, 2008.
3.CISPLATIN.MICROMEDEX(R) Healthcare Series: Thomson Healthcare.; 2008. Accessed.
4.Rosenberg B, Vancamp L, Krigas T. Inhibition of cell division in excherichia coli by electrolysis products from a platinum ecectrode Nature.1965;205:698-699.
5.Jordan P, Carmo-Fonseca M. Molecular mechanisms involved in cisplatin cytotoxicity. Cellular & Molecular Life Sciences. 2000;57(8-9):1229-1235.
6.Muggia FM. Cisplatin update. Seminars in Oncology.1991;18(1 Suppl 3):1-4.
7.Leng M, Brabec V. DNA adducts of cisplatin, transplatin and platinum-intercalating drugs. IARC Scientific Publications. 1994(125):339-348.
8.Ries F, Klastersky J. Nephrotoxicity induced by cancer chemotherapy with special emphasis on cisplatin toxicity. American Journal of Kidney Diseases.1986;8(5):368-379.
9.Leibbrandt ME, Wolfgang GH, Metz AL, Ozobia AA, Haskins JR. Critical subcellular targets of cisplatin and related platinum analogs in rat renal proximal tubule cells. Kidney International. 1995;48(3):761-770.
10.Chu G. Cellular responses to cisplatin. The roles of DNA-binding proteins and DNA repair. Journal of Biological Chemistry. 1994;269(2):787-790.
11.Schrier RW. Diseases of the kidney and urinary tract. Vol 2. 7th ed ed: Philadelphia, PA, USA : Lippincott Williams & Wilkins; 2001.
12.Raymond J.M N, Jonh de vries, Mannfred A. Hollinger. Toxicologie: CRC press 1996.
13.Abeloff MD. Clinical Oncology 3rd ed. New York Churchill Livingstone; 2004.
14.de Jongh FE, van Veen RN, Veltman SJ, de Wit R, van der Burg ME, van den Bent MJ, Planting AS, Graveland WJ, Stoter G, Verweij J. Weekly high-dose cisplatin is a feasible treatment option: analysis on prognostic factors for toxicity in 400 patients. British Journal of Cancer. 2003;88(8):1199-1206.
15.Skeel RT. Handbook of Cancer Chemotherapy. Fifth ed; 2007.
16.Hartmann JT, Knop S, Fels LM, van Vangerow A, Stolte H, Kanz L, Bokemeyer C. The use of reduced doses of amifostine to ameliorate nephrotoxicity of cisplatin/ifosfamide-based chemotherapy in patients with solid tumors. Anti-Cancer Drugs. 2000;11(1):1-6.
17.Santini V, Giles FJ. The potential of amifostine: from cytoprotectant to therapeutic agent. Haematologica. 1999;84(11):1035-1042.
18.Hartmann JT, Fels LM, Knop S, Stolt H, Kanz L, Bokemeyer C. A randomized trial comparing the nephrotoxicity of cisplatin/ifosfamide-based combination chemotherapy with or without amifostine in patients with solid tumors. Invest New Drugs. 2000;18(3):281-289.
19.Kuhlmann MK, Burkhardt G, Kohler H. Insights into potential cellular mechanisms of cisplatin nephrotoxicity and their clinical application. Nephrology Dialysis Transplantation. 1997;12(12):2478-2480.
20.Schuchter LM, Hensley ML, Meropol NJ, Winer EP, American Society of Clinical Oncology Chemotherapy and Radiotherapy Expert P. 2002 update of recommendations for the use of chemotherapy and radiotherapy protectants: clinical practice guidelines of the American Society of Clinical Oncology. Journal of Clinical Oncology.2002;20(12):2895-2903.
21.Daugaard G, Abildgaard U. Cisplatin nephrotoxicity. A review. Cancer Chemotherapy & Pharmacology. 1989;25(1):1-9.
22.Choie DD, Longnecker DS, del Campo AA. Acute and chronic cisplatin nephropathy in rats. Laboratory Investigation. 1981;44(5):397-402.
23.Safirstein R, Winston J, Moel D, Dikman S, Guttenplan J. Cisplatin nephrotoxicity: insights into mechanism. International Journal of Andrology. 1987;10(1):325-346.
24.Meyer KB, Madias NE. Cisplatin nephrotoxicity. Mineral & Electrolyte Metabolism. 1994;20(4):201-213.
25.Litterst CL TI, Guarino AM. Plasma levels and organ distribution of platinum in the rat, dog, and dog fish following intravenous administration of cis-DDP(ll) J Clin Hemat Oncol. 1977;7:169.
26.Alex M. Davison JSC, Jean-pierre Grunfeld, David N.S. Kerr, Eberhard Ritz, Christopher G.Winearls. Oxford Textbook of Clinical Nephrology. Vol 3. 2th edition ed: Oxford ; New York : Oxford University Press; 1998.
27.Berns JS, Ford PA. Renal toxicities of antineoplastic drugs and bone marrow transplantation. Seminars in Nephrology. 1997;17(1):54-66.
28.Schilsky RL, Anderson T. Hypomagnesemia and renal magnesium wasting in patients receiving cisplatin. Annals of Internal Medicine. 1979;90(6):929-931.
29.Lam M, Adelstein DJ. Hypomagnesemia and renal magnesium wasting in patients treated with cisplatin. American Journal of Kidney Diseases. 1986;8(3):164-169.
30.Sutton RA, Walker VR, Halabe A, Swenerton K, Coppin CM. Chronic hypomagnesemia caused by cisplatin: effect of calcitriol. Journal of Laboratory & Clinical Medicine. 1991;117(1):40-43.
31.Winston JA, Safirstein R. Reduced renal blood flow in early cisplatin-induced acute renal failure in the rat. American Journal of Physiology. 1985;249(4 Pt 2):F490-496.
32.Safirstein R, Miller P, Dikman S, Lyman N, Shapiro C. Cisplatin nephrotoxicity in rats: defect in papillary hypertonicity. American Journal of Physiology. 1981;241(2):F175-185.
33.Arany I, Safirstein RL. Cisplatin nephrotoxicity. Seminars in Nephrology. 2003;23(5):460-464.
34.Lau AH. Apoptosis induced by cisplatin nephrotoxic injury. Kidney International. 1999;56(4):1295-1298.
35.Dobyan DC, Levi J, Jacobs C, Kosek J, Weiner MW. Mechanism of cis-platinum nephrotoxicity: II. Morphologic observations. Journal of Pharmacology & Experimental Therapeutics. 1980;213(3):551-556.
36.Ross DA, Gale GR. Reduction of the renal toxicity of cis-dichlorodiammineplatinum(II) by probenecid. Cancer Treatment Reports. 1979;63(5):781-787.
37.Weiner MW, Jacobs C. Mechanism of cisplatin nephrotoxicity. Federation Proceedings. 1983;42(13):2974-2978.
38.Fatima S, Yusufi AN, Mahmood R. Effect of cisplatin on renal brush border membrane enzymes and phosphate transport. Human & Experimental Toxicology. 2004;23(12):547-554.
39.Tsuruya K, Tokumoto M, Ninomiya T, Hirakawa M, Masutani K, Taniguchi M, Fukuda K, Kanai H, Hirakata H, Iida M. Antioxidant ameliorates cisplatin-induced renal tubular cell death through inhibition of death receptor-mediated pathways. American Journal of Physiology - Renal Physiology. 2003;285(2):F208-218.
40.Levi J, Jacobs C, Kalman SM, McTigue M, Weiner MW. Mechanism of cis-platinum nephrotoxicity: I. Effects of sulfhydryl groups in rat kidneys. Journal of Pharmacology & Experimental Therapeutics. 1980;213(3):545-550.
41.Ramesh G, Reeves WB. Inflammatory cytokines in acute renal failure. Kidney International - Supplement. 2004(91):S56-61.
42.Kaushal GP, Kaushal V, Hong X, Shah SV. Role and regulation of activation of caspases in cisplatin-induced injury to renal tubular epithelial cells. Kidney International. 2001;60(5):1726-1736.
43.Nowak G. Protein kinase C-alpha and ERK1/2 mediate mitochondrial dysfunction, decreases in active Na+ transport, and cisplatin-induced apoptosis in renal cells. Journal of Biological Chemistry. 2002;277(45):43377-43388.
44.Rosenberg JM, Sato PH. Cisplatin inhibits in vitro translation by preventing the formation of complete initiation complex. Molecular Pharmacology. 1993;43(3):491-497.
45.Courjault-Gautier F, Le Grimellec C, Giocondi MC, Toutain HJ. Modulation of sodium-coupled uptake and membrane fluidity by cisplatin in renal proximal tubular cells in primary culture and brush-border membrane vesicles. Kidney International. 1995;47(4):1048-1056.
46.Bompart G. Cisplatin-induced changes in cytochrome P-450, lipid peroxidation and drug-metabolizing enzyme activities in rat kidney cortex. Toxicology Letters. 1989;48(2):193-199.
47.Mistry P, Merazga Y, Spargo DJ, Riley PA, McBrien DC. The effects of cisplatin on the concentration of protein thiols and glutathione in the rat kidney. Cancer Chemotherapy & Pharmacology. 1991;28(4):277-282.
48.Galle J. Oxidative stress in chronic renal failure. Nephrology Dialysis Transplantation. 2001;16(11):2135-2137.
49.Shackelford RE, Kaufmann WK, Paules RS. Oxidative stress and cell cycle checkpoint function. Free Radical Biology & Medicine. May 1 2000;28(9):1387-1404.
50.Ichikawa I, Kiyama S, Yoshioka T. Renal antioxidant enzymes: their regulation and function. Kidney International. 1994;45(1):1-9.
51.Halliwell B. The role of oxygen radicals in human disease, with particular reference to the vascular system. Haemostasis. 1993;23 Suppl 1:118-126.
52.Halliwell B. Antioxidant defence mechanisms: from the beginning to the end (of the beginning). Free Radical Research. 1999;31(4):261-272.
53.Klahr S. Oxygen radicals and renal diseases. Mineral & Electrolyte Metabolism. 1997;23(3-6):140-143.
54.Sugiyama S, Hayakawa M, Kato T, Hanaki Y, Shimizu K, Ozawa T. Adverse effects of anti-tumor drug, cisplatin, on rat kidney mitochondria: disturbances in glutathione peroxidase activity. Biochemical & Biophysical Research Communications. 1989;159(3):1121-1127.
55.Schrier RW. Cancer therapy and renal injury. Journal of Clinical Investigation. 2002;110(6):743-745.
56.Goossens V, Grooten J, De Vos K, Fiers W. Direct evidence for tumor necrosis factor-induced mitochondrial reactive oxygen intermediates and their involvement in cytotoxicity. Proceedings of the National Academy of Sciences of the United States of America. 1995;92(18):8115-8119.
57.Ramesh G, Reeves WB. TNFR2-mediated apoptosis and necrosis in cisplatin-induced acute renal failure. American Journal of Physiology - Renal Physiology. 2003;285(4):F610-618.
58.Ramesh G, Reeves WB, Ramesh G, Reeves WB. TNF-alpha mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity. Journal of Clinical Investigation. 2002;110(6):835-842.
59.丁明孝等編著. 細胞分子生物學. 第一版. 台北市: 九州圖書文物有限公司; 2001.
60.Lewin B. Genes VIII: Pearson Prentice Hall; 2004.
61.Price PM, Megyesi J, Safirstein RL. Cell cycle regulation: repair and regeneration in acute renal failure. Seminars in Nephrology. 2003;23(5):449-459.
62.Megyesi J, Udvarhelyi N, Safirstein RL, Price PM. The p53-independent activation of transcription of p21 WAF1/CIP1/SDI1 after acute renal failure. American Journal of Physiology. 1996;271(6):F1211-1216.
63.Megyesi J, Andrade L, Vieira JM, Jr., Safirstein RL, Price PM. Positive effect of the induction of p21WAF1/CIP1 on the course of ischemic acute renal failure. Kidney International. 2001;60(6):2164-2172.
64.Nowak G, Price PM, Schnellmann RG. Lack of a functional p21WAF1/CIP1 gene accelerates caspase-independent apoptosis induced by cisplatin in renal cells. American Journal of Physiology - Renal Physiology. 2003;285(3):F440-450.
65.Megyesi J, Safirstein RL, Price PM, Megyesi J, Safirstein RL, Price PM. Induction of p21WAF1/CIP1/SDI1 in kidney tubule cells affects the course of cisplatin-induced acute renal failure. Journal of Clinical Investigation. 1998;101(4):777-782.
66.Yasuda H, Kato A, Miyaji T, Zhou H, Togawa A, Hishida A. Insulin-like growth factor-I increases p21 expression and attenuates cisplatin-induced acute renal injury in rats. Clinical & Experimental Nephrology. 2004;8(1):27-35.
67.Price PM, Safirstein RL, Megyesi J. Protection of renal cells from cisplatin toxicity by cell cycle inhibitors. American Journal of Physiology - Renal Physiology. 2004;286(2):F378-384.
68.Zhou H, Kato A, Yasuda H, Miyaji T, Fujigaki Y, Yamamoto T, Yonemura K, Hishida A. The induction of cell cycle regulatory and DNA repair proteins in cisplatin-induced acute renal failure. Toxicology & Applied Pharmacology. 2004;200(2):111-120.
69.Miyaji T, Kato A, Yasuda H, Fujigaki Y, Hishida A. Role of the increase in p21 in cisplatin-induced acute renal failure in rats. Journal of the American Society of Nephrology. 2001;12(5):900-908.
70.Lin Z, Lim S, Viani MA, Sapp M, Lim MS. Down-regulation of telomerase activity in malignant lymphomas by radiation and chemotherapeutic agents. American Journal of Pathology. 2001;159(2):711-719.
71.Shankland SJ, Wolf G, Shankland SJ, Wolf G. Cell cycle regulatory proteins in renal disease: role in hypertrophy, proliferation, and apoptosis. American Journal of Physiology - Renal Physiology. 2000;278(4):F515-529.
72.Benjamin L. Genes VII. 2000.
73.Kelman Z. PCNA: structure, functions and interactions. Oncogene. 1997;14(6):629-640.
74.Miyachi K, Fritzler MJ, Tan EM. Autoantibody to a nuclear antigen in proliferating cells. Journal of Immunology. 1978;121(6):2228-2234.
75.Bravo R, Celis JE. A search for differential polypeptide synthesis throughout the cell cycle of HeLa cells. Journal of Cell Biology. 1980;84(3):795-802.
76.Maga G, Hubscher U. Proliferating cell nuclear antigen (PCNA): a dancer with many partners. Journal of Cell Science. 2003;116(15):3051-3060.
77.Nakajima T, Miyaji T, Kato A, Ikegaya N, Yamamoto T, Hishida A. Uninephrectomy reduces apoptotic cell death and enhances renal tubular cell regeneration in ischemic ARF in rats. American Journal of Physiology. 1996;271(4):F846-853.
78.Sano K, Fujigaki Y, Miyaji T, Ikegaya N, Ohishi K, Yonemura K,Hishida A. Role of apoptosis in uranyl acetate-induced acute renal failure and acquired resistance to uranyl acetate. Kidney International. 2000;57(4):1560-1570.
79.McCormick D, Hall PA, McCormick D, Hall PA. The complexities of proliferating cell nuclear antigen. Histopathology. 1992;21(6):591-594.
80.Celis JE, Madsen P, Celis JE, Madsen P. Increased nuclear cyclin/PCNA antigen staining of non S-phase transformed human amnion cells engaged in nucleotide excision DNA repair. FEBS Letters. 1986;209(2):277-283.
81.賴榮祥. 原色生藥學. 台中市: 創譯出版社; 2000.
82.Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochemical Pharmacology. 1999;58(11):1685-1693.
83.Liu H, Baliga R. Cytochrome P450 2E1 null mice provide novel protection against cisplatin-induced nephrotoxicity and apoptosis. Kidney International. 2003;63(5):1687-1696.
84.Kiefer D, Pantuso T. Panax ginseng. American Family Physician. 2003;68(8):1539-1542.
85.Kitts D, Hu C. Efficacy and safety of ginseng. Public Health Nutrition. 2000;3(4A):473-485.
86.Chang YS, Seo EK, Gyllenhaal C, Block KI. Panax ginseng: a role in cancer therapy? Integrative Cancer Therapies. 2003;2(1):13-33.
87.Shin HR, Kim JY, Yun TK, Morgan G, Vainio H. The cancer-preventive potential of Panax ginseng: a review of human and experimental evidence. Cancer Causes & Control. 2000;11(6):565-576.
88.Ong YC, Yong EL. Panax (ginseng)--panacea or placebo? Molecular and cellular basis of its pharmacological activity. Annals of the Academy of Medicine, Singapore. 2000;29(1):42-46.
89.Gillis CN. Panax ginseng pharmacology: a nitric oxide link? Biochemical Pharmacology. 1997;54(1):1-8.
90.Vogler BK, Pittler MH, Ernst E. The efficacy of ginseng. A systematic review of randomised clinical trials. European Journal of Clinical Pharmacology. 1999;55(8):567-575.
91.Rimar S, Lee-Mengel M, Gillis CN. Pulmonary protective and vasodilator effects of a standardized Panax ginseng preparation following artificial gastric digestion. Pulmonary Pharmacology. 1996;9(4):205-209.
92.Voces J, Alvarez AI, Vila L, Ferrando A, Cabral de Oliveira C, Prieto JG. Effects of administration of the standardized Panax ginseng extract G115 on hepatic antioxidant function after exhaustive exercise. Comparative Biochemistry & Physiology Part C Pharmacology, Toxicology, Endocrinology. 1999;123(2):175-184.
93.Sotaniemi EA, Haapakoski E, Rautio A. Ginseng therapy in non-insulin-dependent diabetic patients. Diabetes Care. 1995;18(10):1373-1375.
94.Jeong TC, Kim HJ, Park JI, Ha CS, Park JD, Kim SI, Roh JK. Protective effects of red ginseng saponins against carbon tetrachloride-induced hepatotoxicity in Sprague Dawley rats. Planta Medica. 1997;63(2):136-140.
95.Cho JY, Yoo ES, Baik KU, Park MH, Han BH. In vitro inhibitory effect of protopanaxadiol ginsenosides on tumor necrosis factor (TNF)-alpha production and its modulation by known TNF-alpha antagonists. Planta Medica. 2001;67(3):213-218.
96.Cheng Y, Shen LH, Zhang JT. Anti-amnestic and anti-aging effects of ginsenoside Rg1 and Rb1 and its mechanism of action. Acta Pharmacologica Sinica. Feb 2005;26(2):143-149.
97.Chen XC, Zhou YC, Chen Y, Zhu YG, Fang F, Chen LM. Ginsenoside Rg1 reduces MPTP-induced substantia nigra neuron loss by suppressing oxidative stress. Acta Pharmacologica Sinica. 2005;26(1):56-62.
98.Chen XC, Zhu YG, Zhu LA, Huang C, Chen Y, Chen LM, Fang F, Zhou YC, Zhao CH. Ginsenoside Rg1 attenuates dopamine-induced apoptosis in PC12 cells by suppressing oxidative stress. European Journal of Pharmacology. 2003;473(1):1-7.
99.Chen XC, Fang F, Zhu YG, Chen LM, Zhou YC, Chen Y. Protective effect of ginsenoside Rg1 on MPP+-induced apoptosis in SHSY5Y cells. Journal of Neural Transmission. 2003;110(8):835-845.
100.Leung KW, Cheng YK, Mak NK, Chan KK, Fan TP, Wong RN. Signaling pathway of ginsenoside-Rg1 leading to nitric oxide production in endothelial cells. FEBS Lett. 2006;580(13):3211-3216.
101.Lu JP, Ma ZC, Yang J, Huang J, Wang SR, Wang SQ. Ginsenoside Rg1-induced alterations in gene expression in TNF-alpha stimulated endothelial cells. Chinese Medical Journal. 2004;117(6):871-876.
102.Zhang HS, Wang SQ. Ginsenoside Rg1 inhibits tumor necrosis factor-alpha (TNF-alpha)-induced human arterial smooth muscle cells (HASMCs) proliferation. Journal of Cellular Biochemistry. 2006;98(6):1471-1481.
103.Wu CF, Bi XL, Yang JY, Zhan JY, Dong YX, Wang JH, Wang JM, Zhang R, Li X. Differential effects of ginsenosides on NO and TNF-alpha production by LPS-activated N9 microglia. Int Immunopharmacol. 2007;7(3):313-320.
104.Alfred Goodman Gliman TWR, Palmer Taylor. Goodman&Gliman''s The Pharmacological Basis of Therapeutics(ed, Insel,PA): Macmillan Publishing Company; 1990.
105.Holdiness MR. Clinical pharmacokinetics of N-acetylcysteine. Clin Pharmacokinet. 1991;20(2):123-134.
106.Product Information: Acetylcysteine Solution, acetylcysteine solution, USP. Columbus, OH, USA: Roxane Laboratories, Inc; 2001.
107.Peterson RG, Rumack BH. Treating acute acetaminophen poisoning with acetylcysteine. JAMA. 1977;237(22):2406-2407.
108.Safirstein R, Andrade L, Vieira JM. Acetylcysteine and nephrotoxic effects of radiographic contrast agents--a new use for an old drug. N Engl J Med. Jul 20 2000;343(3):210-212.
109.Rumack BH, Peterson RG. Acetaminophen toxicity. West J Med. 1980;132(1):61.
110.Peterson RG, Rumack BH. Toxicity of acetaminophen overdose. JACEP. 1978;7(5):202-205.
111.Peterson RG, Rumack BH. N-acetylcysteine for acetaminophen overdosage (cont.). N Engl J Med. 1977;296(9):515.
112.Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med. 2000;343(3):180-184.
113.Salahudeen A, Poovala V, Parry W, Pande R,Kanji V, Ansari N, Morrow J, Roberts J. Cisplatin induces N-acetyl cysteine suppressible F2-isoprostane production and injury in renal tubular epithelial cells. Journal of the American Society of Nephrology. 1998;9(8):1448-1455.
114.DiMari J, Megyesi J, Udvarhelyi N, Price P, Davis R, Safirstein R. N-acetyl cysteine ameliorates ischemic renal failure. Am J Physiol. 1997;272(3 Pt 2):F292-298.
115.Salom MG, Ramirez P, Carbonell LF, Lopez Conesa E, Cartagena J, Quesada T, Parrilla P, Fenoy FJ. Protective effect of N-acetyl-L-cysteine on the renal failure induced by inferior vena cava occlusion. Transplantation. 1998;65(10):1315-1321.
116.Yano T, Itoh Y, Matsuo M, Kawashiri T, Egashira N, Oishi R. Involvement of both tumor necrosis factor-alpha-induced necrosis and p53-mediated caspase-dependent apoptosis in nephrotoxicity of cisplatin. Apoptosis. 2007;12(10):1901-1909.
117.Sheikh-Hamad D, Timmins K, Jalali Z. Cisplatin-induced renal toxicity: possible reversal by N-acetylcysteine treatment. Journal of the American Society of Nephrology. 1997;8(10):1640-1644.
118.Appenroth D, Winnefeld K, Schroter H, Rost M. Beneficial effect of acetylcysteine on cisplatin nephrotoxicity in rats. J Appl Toxicol. 1993;13(3):189-192.
119.Appenroth D, Braunlich H. Age differences in cisplatinum nephrotoxicity. Toxicology. 1984;32(4):343-353.
120.Appenroth D, Winnefeld K. Role of glutathione for cisplatin nephrotoxicity in young and adult rats. Ren Fail. 1993;15(2):135-139.
121.Mishima K, Baba A, Matsuo M, Itoh Y, Oishi R. Protective effect of cyclic AMP against cisplatin-induced nephrotoxicity. Free Radical Biology & Medicine. 2006;40(9):1564-1577.
122.Babu E, Gopalakrishnan VK, Sriganth IN, Gopalakrishnan R, Sakthisekaran D. Cisplatin induced nephrotoxicity and the modulating effect of glutathione ester. Mol Cell Biochem. 1995;144(1):7-11.
123.Ramesh G, Reeves WB. Salicylate reduces cisplatin nephrotoxicity by inhibition of tumor necrosis factor-alpha. Kidney Int. 2004;65(2):490-499.
124.Ramesh G, Reeves WB. Inflammatory cytokines in acute renal failure. Kidney Int Suppl. 2004(91):S56-61.
125.Ramesh G, Reeves WB. p38 MAP kinase inhibition ameliorates cisplatin nephrotoxicity in mice. Am J Physiol Renal Physiol. 2005;289(1):F166-174.
126.Kim YW, Song DK, Kim WH, Lee KM, Wie MB, Kim YH, Kee SH, Cho MK. Long-term oral administration of ginseng extract decreases serum gamma-globulin and IgG1 isotype in mice. Journal of Ethnopharmacology. 1997;58(1):55-58.
127.Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry. 1976;72:248-254.
128.張惠婷. 順氯氨鉑引發的腎毒性在純系小鼠的確立與柴胡在此腎炎模型的藥效評估. 台北市: 藥學系碩士班, 臺北醫學大學; 2005.
129.邱芷瑩. 人參與人參皂苷在順氯氨鉑引發的腎毒性於純系小鼠的藥效評估. 台北市: 藥學系碩士班, 臺北醫學大學; 2007.
130.Hultberg B, Ravnskov U. The excretion of N-acetyl-beta-glucosaminidase in glomerulonephritis. Clinical Nephrology. 1981;15(1):33-38.
131.Yokozawa T, Zhou JJ, Hattori M, Inaba S, Okada T, Oura H. Effects of ginseng in nephrectomized rats. Biological & Pharmaceutical Bulletin. 1994;17(11):1485-1489.
132.Han SW, Kim H. Ginsenosides stimulate endogenous production of nitric oxide in rat kidney. International Journal of Biochemistry & Cell Biology. May 1996;28(5):573-580.
133.Hattori T, Ito M, Suzuki Y, Hattori T, Ito M, Suzuki Y. Studies on antinephritic effects of plant components in rats (2): Effects of ginsenosides on original-type anti-GBM nephritis in rats and its mechanisms. Nippon Yakurigaku Zasshi - Folia Pharmacologica Japonica. 1991;97(2):127-134.
134.Wang Y, Wang BX, Liu TH, Minami M, Nagata T, Ikejima T. Metabolism of ginsenoside Rg1 by intestinal bacteria. II. Immunological activity of ginsenoside Rg1 and Rh1. Acta Pharmacol Sin. 2000;21(9):792-796.
135.Cho JY, Yoo ES, Baik KU, Park MH, Han BH. In vitro inhibitory effect of protopanaxadiol ginsenosides on tumor necrosis factor (TNF)-alpha production and its modulation by known TNF-alpha antagonists. Planta Med. 2001;67(3):213-218.
136.Park EK, Choo MK, Han MJ, Kim DH. Ginsenoside Rh1 possesses antiallergic and anti-inflammatory activities. Int Arch Allergy Immunol. 2004;133(2):113-120.
137.Shin YW, Bae EA, Kim SS, Lee YC, Kim DH. Effect of ginsenoside Rb1 and compound K in chronic oxazolone-induced mouse dermatitis. Int Immunopharmacol. 2005;5(7-8):1183-1191.
138.Park EK, Shin YW, Lee HU, Kim SS, Lee YC, Lee BY, Kim DH. Inhibitory effect of ginsenoside Rb1 and compound K on NO and prostaglandin E2 biosyntheses of RAW264.7 cells induced by lipopolysaccharide. Biol Pharm Bull. 2005;28(4):652-656.
139.Chen SM, Sato N, Yoshida M, Satoh N, Ueda S. Effects of Bupleurum scorzoneraefolium, Bupleurum falcatum, and saponins on nephrotoxic serum nephritis in mice. J Ethnopharmacol. 2008;116(3):397-402.
140.Leung KW, Leung FP, Huang Y, Mak NK, Wong RN. Non-genomic effects of ginsenoside-Re in endothelial cells via glucocorticoid receptor. FEBS Lett. 2007;581(13):2423-2428.
141.Yang CS, Ko SR, Cho BG,Shin D, Yuk JM, Li S, Kim JM, Evans RM, Jung JS, Song DK, Jo EK. The Ginsenoside Metabolite Compound K, a Novel Agonist of Glucocorticoid Receptor, Induces Tolerance to Endotoxin-induced Lethal Shock. J Cell Mol Med. 2007.
142.Dickey DT, Wu YJ, Muldoon LL, Neuwelt EA. Protection against cisplatin-induced toxicities by N-acetylcysteine and sodium thiosulfate as assessed at the molecular, cellular, and in vivo levels. Journal of Pharmacology & Experimental Therapeutics. 2005;314(3):1052-1058.
143.Luo J, Tsuji T, Yasuda H, Sun Y, Fujigaki Y, Hishida A. The molecular mechanisms of the attenuation of cisplatin-induced acute renal failure by N-acetylcysteine in rats. Nephrol Dial Transplant. 2008.
144.Anderson ME, Naganuma A, Meister A. Protection against cisplatin toxicity by administration of glutathione ester. FASEB J. 1990;4(14):3251-3255.
145.Wu YJ, Muldoon LL, Neuwelt EA. The chemoprotective agent N-acetylcysteine blocks cisplatin-induced apoptosis through caspase signaling pathway. Journal of Pharmacology & Experimental Therapeutics. 2005;312(2):424-431.
146.Sekharam M, Trotti A, Cunnick JM, Wu J. Suppression of fibroblast cell cycle progression in G1 phase by N-acetylcysteine. Toxicol Appl Pharmacol. 1998;149(2):210-216.
147.Doolan PD, Alpen EL, Theil GB. A clinical appraisal of the plasma concentration and endogenous clearance of creatinine. Am J Med. 1962;32:65-79.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊
 
系統版面圖檔 系統版面圖檔