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研究生:吳姿慧
研究生(外文):Tzu-Hui Wu
論文名稱:槲黃素奈米新劑型之物理化學性質探討及其抗氧化、保肝活性之開發研究
論文名稱(外文):Preparation and physicochemical assessment of novel quercetin nanoparticle, and investigation on its antioxidant and hepatoprotective activities
指導教授:林俊清林俊清引用關係
指導教授(外文):Chun-Ching Lin
學位類別:博士
校院名稱:高雄醫學大學
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:2009
畢業學年度:97
語文別:中文
論文頁數:100
中文關鍵詞:槲黃素奈米急性肝損傷抗氧化抗發炎
外文關鍵詞:Quercetinnanoparticlesacute liver failureantioxidationanti-inflammation
相關次數:
  • 被引用被引用:1
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  • 收藏至我的研究室書目清單書目收藏:1
背景及目的:槲黃素是知名可被用來預防急性肝損傷天然化合物之一,但是它難溶於水的特性則限制其臨床上的應用。本研究的目的為發展一個新穎槲黃素奈米製劑,以期改善其溶解度並且增加體外抗氧化及口服體內之保肝活性。
材料及方法:槲黃素奈米製劑物理化學鑑定包含平均粒徑大小、產率、包埋率、穿透式顯微鏡、溶離試驗、示差掃描熱分析、X光繞射及傅立葉轉換紅外光譜儀等分析。在體外試驗比較槲黃素及其奈米製劑的抗氧化藥理活性;在體內試驗則是先利用乙醯氨基酚引發急性肝損傷之動物模式後,再來評估槲黃素及其奈米製劑的抗氧化、抗發炎及保肝等活性。
結果與討論:由體外溶離試驗結果證實槲黃素奈米製劑釋出速率較槲黃素增加74倍,其釋出機轉為降低藥品平均粒徑、非晶形結構及分子間氫鍵產生等特性。另外,有關槲黃素奈米在體外抗氧化活性檢測包含清除DPPH試驗、超氧自由基清除之活性、超氧自由基生成之抑制作用及抗脂質過氧化等試驗都證實比槲黃素更具活性(P < 0.05)。除此之外,槲黃素奈米也進行體內保肝活性並且證實比槲黃素更具療效,歸咎其藥理活性為降低急性肝損傷動物血清中肝功能指數及發炎性細胞激素釋出;增加肝臟抗氧化酵素及降低脂質過氧化等特性 (P < 0.05)。
結論:奈米新劑型在研究中證實能有效改善槲黃素的釋出,在進行急性肝損傷動物試驗中產生較佳的保肝活性,其主要機轉是透過抗氧化及抗發炎作用所致。
Background/Purpose: Quercetin (QU) is known to exert pharmacological effects against acute liver failure (ALF), but its poor aqueous solubility has restricted its clinical applications. Therefore, a novel quercetin-loaded nanoparticles system (QUEN) was developed to resolve the restricted water solubility of QU and to enhance its antioxidant activities in vitro and hepatoprotective effects in vivo on oral administration.
Materials and Methods: Physicochemical characterizations of QUEN included assessment of particle size, morphology, yield, and encapsulation efficiencies, differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), fourier transform infrared spectroscopy (FT-IR), and dissolution study. In addition, to evaluate its antioxidant activities in vitro and its oral treatment potential against ALF, the studies compared the antioxidant and hepatoprotective effects of QUEN and QU on acetaminophen (APAP)-induced ALF in rats.
Results and Discussion: The release of the drug from the QUEN was 74-folds higher compared with the pure drug. The release mechanisms of QU from the QUEN were attributed to the reduction of drug particle size, the formation of high-energy amorphous state, and the intermolecular hydrogen bonding. The antioxidant activities in vitro of the QUEN were observed to be more effective than pure QU on DPPH scavenging, anti-superoxide formation, superoxide anion scavenging, and anti-lipid peroxidation. Moreover, QUEN also exhibited more hepatoprotective effects compared to QU with considerable reduction in the serum levels of liver function index and pro-inflammatory cytokines, an increase in the levels of hepatic antioxidant enzymes, and a decrease in lipid peroxidation (P < 0.05).
Conclusion: QUEN effectively improved the release of QU which resulted in more hepatoprotective effects mediated by its antioxidant and anti-inflammatory properties against ALF.
目 錄
圖次目錄-------------------------------------------------I
表次目錄-----------------------------------------------III
誌謝----------------------------------------------------IV
中文摘要------------------------------------------------V
英文摘要-----------------------------------------------VII

第一章 緒論---------------------------------------------1
第一節 自由基簡介----------------------------------------1
第二節 急性肝損傷簡介------------------------------------3
第三節 乙醯氨基酚誘發急性肝損傷機轉----------------------4
第四節 槲黃素簡介----------------------------------------8
第五節 奈米製劑-----------------------------------------10
第六節 研究目的-----------------------------------------13
第七節 全名與縮寫---------------------------------------14
第二章 實驗材料及方法----------------------------------16
第一節 材料---------------------------------------------16
第二節 槲黃素分析方法-----------------------------------17
一、HPLC分析系統及條件建立------------------------------17
二、線性------------------------------------------------17
第三節 槲黃素奈米處方製備方法---------------------------18
一、物理混合處方----------------------------------------18
二、奈米製劑處方----------------------------------------18
第四節 奈米處方物理化學性質檢測-------------------------19
一、奈米粒子大小之測定----------------------------------19
二、奈米處方產率及包埋率測定----------------------------19
(一)產率測定--------------------------------------------19
(二)包埋率測定------------------------------------------19
三、穿透式電子顯微鏡 (TEM)測定--------------------------20
四、示差掃描熱分析儀 (DSC)測定--------------------------20
五、X射線粉末散射儀 (XRD)測定---------------------------20
六、傅立葉變換紅外發射光譜 (FT-IR)測定------------------21
七、體外溶試驗評估--------------------------------------21
第五節 體外抗氧化活性評估-------------------------------22
一、清除2 ,2-diphenyl-1-picrylhydrazyl (DPPH)試驗-----22
二、超氧自由基清除之活性--------------------------------22
三、超氧自由基生成之抑制活性----------------------------23
四、抗脂質過氧化作用------------------------------------23
第六節 體內保肝活性評估---------------------------------25
一、實驗動物分組及誘發大鼠急性肝損傷--------------------25
二、血清肝功能生化指數測定------------------------------26
三、組織病理學的觀察------------------------------------26
四、肝臟超氧歧化酶(SOD)活性分析-------------------------26
五、肝臟過氧化氫酶(CAT)活性分析-------------------------27
六、Glutathione peroxidase(GPx)活性分析-----------------28
七、抑制脂質過氧化活性試驗------------------------------29
八、RT-PCR分析肝細胞促發炎因子 (TNF-α及IL-1β)-----------31
九、促發炎因子 (TNF-α及IL-1β)之含量測定----------------32
十、統計分法--------------------------------------------33
第三章 結果與討論--------------------------------------34
第一節 奈米製劑物化性質研究-----------------------------34
一、粒徑及分佈情形--------------------------------------34
二、產率及包埋率探討------------------------------------34
三、示差掃描熱分析--------------------------------------35
四、X射線粉末繞射儀-------------------------------------35
五、傅立葉變換紅外發射光譜------------------------------36
六、槲黃素釋出速率--------------------------------------36
第二節 體外抗氧化活性-----------------------------------38
一、清除DPPH測定----------------------------------------38
二、超氧自由基生成抑制作用及超氧自由基清除活性----------39
三、抗脂質過氧化作用------------------------------------39
第三節 體內動物試驗-------------------------------------41
一、肝功能生化值----------------------------------------41
二、肝臟組織病理切片------------------------------------41
三、肝臟抗氧化酶----------------------------------------42
四、肝臟脂質過氧化--------------------------------------43
五、促發炎因子 (TNF-α及IL-1β)-------------------------44
六、QUEN在預防急性肝損傷之優勢--------------------------45
第四章 本研究重點回顧分析------------------------------47
第一節、QUEN體內/體外分析-------------------------------47
第二節、體外抗氧化/體內保肝活性機轉分析-----------------49
第五章 結論--------------------------------------------51
第六章 未來展望----------------------------------------52
第七章 參考文獻----------------------------------------54
第八章 圖表--------------------------------------------71
期刊與學會論文發表--------------------------------------84
Ader, P., Wessmann, A., Wolffram, S., 2000. Bioavailability and metabolism of the flavonol quercetin in the pig. Free. Radic. Biol. Med. 28, 1056-1067.
Aebi, H., 1984. Catalase in vitro. Methods. Enzymol. 105, 121-126.
Bauer, I., Vollmar, B., Jaeschke, H., Rensing, H., Kraemer, T., Larsen, R., Bauer, M., 2000. Transcriptional activation of heme oxygenase-1 and its functional significance in acetaminophen-induced hepatitis and hepatocellular injury in the rat. J. Hepatol. 33, 395-406.
Bilati, U., Allémann, E., Doelker, E., 2005. Development of a nanoprecipitation method intended for the entrapment of hydrophilic drugs into nanoparticles. Eur. J. Pharm. Sci. 24, 67-75.
Blazka, M.E., Wilmer, J.L., Holladay, S.D., Wilson, R.E., Luster, M.I. 1995. Role of proinflammatory cytokines in acetaminophen hepatotoxicity. Toxicol. Appl. Pharmacol. 133, 43-52.
Blazka, M.E., Elwell, M.R., Holladay, S.D., Wilson, R.E., Luster, M.I., 1996. Histopathology of acetaminophen-induced liver changes: role of interleukin 1 alpha and tumor necrosis factor alpha. Toxicol. Pathol. 24, 181-189.
Borish, L., Rosenwasser, L.J., 1996. Update on cytokines. J. Allergy. Clin. Immunol. 97, 719-733.
Brigger, I., Dubernet, C., Couvreur, P., 2002. Nanoparticles in cancer therapy and diagnosis. Adv. Drug. Deliv. Rev. 54, 631-651.
Conrad, M., Schneider, M., Seiler, A., Bornkamm, G.W., 2007. Physiological role of phospholipid hydroperoxide glutathione peroxidase in mammals. Biol. Chem. 388, 1019-1025.
Dinarello, C.A., 1991. Interleukin-1 and interleukin-1 antagonism. Blood. 77, 1627-1652.
Chang, W.S., Chang, Y.H., Lu, F.J., Chiang, H.C., 1994. Inhibitory effects of phenolics on xanthine oxidase. Anticancer. Res. 14, 501-506.
Chen, Y., Liu, J., Yang, X., Zhao, X., Xu, H., 2005. Oleanolic acid nanosuspensions: preparation, in-vitro characterization and enhanced hepatoprotective effect. J. Pharm. Pharmacol. 57, 259-264.
Comalada, M., Camuesco, D., Sierra, S., Ballester, I., Xaus, J., Galvez, J., Zarzuelo, A., 2005. In vivo quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through down-regulation of the NF-kappaB pathway. Eur. J. Immunol. 35, 584-592.
Day, B.J., 2008. Catalase and glutathione peroxidase mimics. Biochem Pharmacol. (in press).
Deharo, E., Bourdy, G., Quenevo, C., Muñoz, V., Ruiz, G., Sauvain, M., 2001. A search for natural bioactive compounds in Bolivia through a multidisciplinary approach. Part V. Evaluation of the antimalarial activity of plants used by the Tacana Indians. : J Ethnopharmacol. 77, 91-98.
Exarchou, V., Nenadis, N., Tsimidou, M., Gerothanassis, I.P., Troganis, A., Boskou, D., 2002. Antioxidant activities and phenolic composition of extracts from Greek oregano, Greek sage, and summer savory. J. Agric. Food. Chem. 50, 5294-5299.
Fakurazi, S., Hairuszah, I., Nanthini, U., 2008. Moringa oleifera Lam prevents acetaminophen induced liver injury through restoration of glutathione level. Food. Chem. Toxicol. 46, 2611-2615.
Fessi, H., Puiseux, F., Devissaguet, J.P., Ammoury, N., Benita, S., 1989. Nanocapsule formation by interracial polymer deposition following solvent displacement. Int. J. Pharm. 55, R1-R4.
Fernandez-Panchon, M.S., Villano, D., Troncoso, A.M., Garcia-Parrilla, M.C., 2008. Antioxidant activity of phenolic compounds: from in vitro results to in vivo evidence. Crit. Rev. Food. Sci. Nutr. 48, 649-671.
Fernández-Urrusuno, R., Fattal, E., Féger, J., Couvreur, P., Thérond, P., 1997. Evaluation of hepatic antioxidant systems after intravenous administration of polymeric nanoparticles. Biomaterials. 18, 511-517.
Galindo-Rodriguez, S., Allemann, E., Fessi, H., Doelker, E., 2004. Physicochemical parameters associated with nanoparticle formation in the salting-out, emulsification-diffusion, and nanoprecipitation methods. Pharm. Res. 21, 1428-1439.
Gill, R.Q., Sterling, R.K., 2001. Acute liver failure. J. Clin. Gastroenterol. 33, 191-198.
Gohil, K., Moy, R.K., Farzin, S., Maguire, J.J., Packer, L., 2000. mRNA expression profile of a human cancer cell line in response to Ginkgo biloba extract: induction of antioxidant response and the Golgi system. Free. Radic. Res. 33, 831-849.
Gugler, R., Leschik, M., Dengler, H.J., 1975. Disposition of quercetin in man after single oral and intravenous doses. Eur. J. Clin. Pharmacol. 9, 229-234.
Hashida, M., Takemura, S., Nishikawa, M., Takakura, Y. 1998. Targeted delivery of plasmid DNA complexed with galactosylated poly(L-lysine). J. Control. Release. 53, 301-310.
Heim, K.E., Tagliaferro, A.R., Bobilya, D.J., 2002. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J. Nutr. Biochem. 13, 572-584.
Hertog, M.G.L., Hollman, P.C.H., Venema, D.P., 1992. Optimization of a quantitative HPLC determination of potentially anticarcinogenic flavonoids in vegetables and fruits. J. Agric. Food. Chem. 40, 1591–1598.
Holt, M.P., Ju, C., 2006. Mechanisms of drug-induced liver injury. AAPS. J. 8, E48-54.
Horisawa, E., Danjo, K., Haruna, M., 2000. Physical properties of solid dispersion of a nonsteroidal anti-inflammatory drug (M-5011) with Eudragit E. Drug. Dev. Ind. Pharm. 26, 1271-1278.
Hu, Y., Xie, J., Tong, Y.W., Wang, C.H., 2007. Effect of PEG conformation and particle size on the cellular uptake efficiency of nanoparticles with the HepG2 cells. J. Control. Release. 118, 7-17.
Inal, M.E., Kahraman, A., 2000. The protective effect of flavonol quercetin against ultraviolet A induced oxidative stress in rats. Toxicology. 154, 21–29.
James, L.P., Mayeux, P.R., Hinson, J.A., 2003. Acetaminophen-induced hepatotoxicity. Drug. Metab. Dispos. 31, 1499-1506.
James, L.P., Simpson, P.M., Farrar, H.C., Kearns, G.L., Wasserman, G.S., Blumer, J.L., Reed, M.D., Sullivan, J.E., Hinson, J.A., 2005. Cytokines and toxicity in acetaminophen overdose. J. Clin. Pharmacol. 45, 1165-1171.
Janbaz, K.H., Saeed, S.A., Gilani, A.H., 2004. Studies on the protective effects of caffeic acid and quercetin on chemical-induced hepatotoxicity in rodents. Phytomedicine. 11, 424-430.
Jung, J.Y., Yoo, S.D., Lee, S.H., Kim, K.H., Yoon, D.S., Lee, K.H., 1999. Enhanced solubility and dissolution rate of itraconazole by a solid dispersion technique. Int. J. Pharm. 187, 209-218.
Justino, G.C., Santos, M.R., Canário, S., Borges, C., Florêncio, M.H., Mira, L. 2004. Plasma quercetin metabolites: structure-antioxidant activity relationships. Arch. Biochem. Biophys. 432, 109-121.
Kanadaswami, C., Lee, L.T., Lee, P.P., Hwang, J.J., Ke, F.C., Huang, Y.T., Lee, M.T., 2005. The antitumor activities of flavonoids. In Vivo. 19, 895-909.
Kerem, Z., Bravdo, B.A., Shoseyov, O., Tugendhaft, Y., 2004. Rapid liquid chromatography-ultraviolet determination of organic acids and phenolic compounds in red wine and must. J. Chromatogr. A. 1052, 211-215.
Khaled, K.A., El-Sayed, Y.M., Al-Hadiya, B.M., 2003. Disposition of the flavonoid quercetin in rats after single intravenous and oral doses. Drug. Dev. Ind. Pharm. 29, 397-403.
Khalil, N.M., Pepato, M.T., Brunetti, I.L., 2008. Free radical scavenging profile and myeloperoxidase inhibition of extracts from antidiabetic plants: Bauhinia forficata and Cissus sicyoides. Biol. Res. 41, 165-171.
Kim, S.Y., Kim, T.B., Moon, K.A., Kim, T.J., Shin, D., Cho, Y.S., Moon, H.B., Lee, K.Y., 2008. Regulation of pro-inflammatory responses by lipoxygenases via intracellular reactive oxygen species in vitro and in vivo. Exp. Mol. Med. 40, 461-476.
Kocyigit, A., Gur, S., Gurel, M.S., Bulut, V., Ulukanligil, M., 2002. Antimonial therapy induces circulating proinflammatory cytokines in patients with cutaneous leishmaniasis. Infect. Immun. 70, 6589-6591.
Kreuter, J., 1994. Colloidal drug delivery systems. Marcel Dekker, New York, Chapter 5, 219-261.
Kuvandik, G., Duru, M., Nacar, A., Yonden, Z., Helvaci, R., Koc, A., Kozlu, T., Kaya, H., Sogüt, S., 2008. Effects of erdosteine on acetaminophen-induced hepatotoxicity in rats. Toxicol. Pathol. 36, 714-719.
Larson, A.M., Polson, J., Fontana, R.J., Davern, T.J., Lalani, E., Hynan, L.S., Reisch, J.S., Schiødt, F.V., Ostapowicz, G., Shakil, A.O., Lee, W.M., 2005. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. 42, 1364-1372.
Laskin, D.L., Heck, D.E., Laskin, J.D. 1998. Role of inflammatory cytokines and nitric oxide in hepatic and pulmonary toxicity. Toxicol. Lett. 102, 289-293.
Lee, C.W., Lin, C.C., Luo, S.F., Lee, H.C., Lee, I.T., Aird, W.C., Hwang, T.L., Yang, C.M., 2008. Tumor necrosis factor-alpha enhances neutrophil adhesiveness: induction of vascular cell adhesion molecule-1 via activation of Akt and CaM kinase II and modifications of histone acetyltransferase and histone deacetylase 4 in human tracheal smooth muscle cells. Mol. Pharmacol. 73, 1454-1464.
Lee, E.S., Lee, H.E., Shin, J.Y., Yoon, S., Moon, J.O., 2003. The flavonoid quercetin inhibits dimethylnitrosamine-induced liver damage in rats. J. Pharm. Pharmacol. 55, 1169-1174.
Li, Y., Wang, E., Patten, C.J., Chen, L., Yang, C.S., 1994. Effects of flavonoids on cytochrome P450-dependent acetaminophen metabolism in rats and human liver microsomes. Drug. Metab. Dispos. 22, 566-571.
Liang, H.F., Yang, T.F., Huang, C.T., Chen, M.C., Sung, H.W., 2005. Preparation of nanoparticles composed of poly(gamma-glutamic acid)-poly(lactide) block copolymers and evaluation of their uptake by HepG2 cells. J. Control. Release. 105, 213-225.
Limayem Blouza, I., Charcosset, C., Sfar, S., Fessi, H., 2006. Preparation and characterization of spironolactone-loaded nanocapsules for paediatric use. Int. J. Pharm. 325, 124-131.
Lin, C.C., Tsai, C.C., Yen, M.H., 1995. The evaluation of hepatoprotective effects of Taiwan folk medicine ''teng-khia-u''. J. Ethnopharmacol. 45, 113-123.
Liu, B., Anderson, D., Ferry, D.R., Seymour, L.W., de Takats, P.G., Kerr, D.J., 1995. Determination of quercetin in human plasma using reversed-phase high-performance liquid chromatography. J. Chromatogr. B. Biomed. Appl. 666, 149-155.
Lowry, O.H., Rosebrough, N.J., Farr, A.L. Randall, R.J., 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193, 265-275.
Luster, M.I., Simeonova, P.P., Gallucci, R.M., Bruccoleri, A., Blazka, M.E., Yucesoy, B., 2001. Role of inflammation in chemical-induced hepatotoxicity. Toxicol. Lett. 120, 317-321.
McCord, J.M., Fridovich, I., 1969. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J. Biol. Chem. 244, 6049-6055.
Memişoğlu, E., Bochot, A., Ozalp, M., Sen, M., Duchêne, D., Hincal, A.A., 2003. Direct formation of nanospheres from amphiphilic beta-cyclodextrin inclusion complexes. Pharm. Res. 20(1), 117-125.
Mu, X., Zhong, Z., 2006. Preparation and properties of poly(vinyl alcohol)-stabilized liposomes. Int. J. Pharm. 318, 55-61.
Mulholland, P.J., Ferry, D.R., Anderson, D., Hussain, S.A., Young, A.M., Cook, J.E., Hodgkin, E., Seymour, L.W., Kerr, D.J., 2001. Pre-clinical and clinical study of QC12, a water-soluble, pro-drug of quercetin. Ann. Oncol. 12, 245-248.
Nagy, M., Spilková, J., Vrchovská, V., Kontseková, Z., Sersen, F., Mucaji, P., Grancai, D., 2006. Free radical scavenging activity of different extracts and some constituents from the leaves of Ligustrum vulgare and L. delavayanum. Fitoterapia. 77, 395-397.
Ohkawa, H., Ohishi, N., Yagi, K., 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 95, 351-358.
Palumbo, M., Russo, A., Cardile, V., Renis, M., Paolino, D., Puglisi, G., Fresta, M., 2002. Improved antioxidant effect of idebenone-loaded polyethyl-2-cyanoacrylate nanocapsules tested on human fibroblasts. Pharm. Res. 19, 71-78.
Pari, L., Murugavel, P., 2004. Protective effect of alpha-lipoic acid against chloroquine-induced hepatotoxicity in rats. J. Appl. Toxicol. 24(1), 21-26.
Pietta, P.G., 2000. Flavonoids as antioxidants. J. Nat. Prod. 63, 1035-1042.
Ratnam, D.V., Ankola, D.D., Bhardwaj, V., Sahana, D.K., Kumar, M.N., 2006. Role of antioxidants in prophylaxis and therapy: A pharmaceutical perspective. J. Control. Release. 113, 189-207.
Reyes-Gordillo, K., Segovia, J., Shibayama, M., Vergara, P., Moreno, M.G., Muriel P., 2007. Curcumin protects against acute liver damage in the rat by inhibiting NF-kappaB, proinflammatory cytokines production and oxidative stress. Biochim. Biophys. Acta. 1770, 989-996.
Sahoo, S.K., Panyam. J., Prabha. S., Labhasetwar. V., 2002. Residual polyvinyl alcohol associated with poly (D, L-lactide-co-glycolide) nanoparticles affects their physical properties and cellular uptake. J. Control. Release. 82, 105-114.
Salazar-Montes, A., Delgado-Rizo, V., Armendáriz-Borunda, J., 2000. Differential gene expression of pro-inflammatory and anti-inflammatory cytokines in acute and chronic liver injury. Hepatol. Res. 16, 181-194.
Schaffazick, S.R., Pohlmann, A.R., de Cordova, C.A., Creczynski-Pasa, T.B., Guterres, S.S., 2005. Protective properties of melatonin-loaded nanoparticles against lipid peroxidation. Int. J. Pharm. 289, 209-213.
Sehra, S., Dhake, A.S., 2005. Formulation and evaluation of sustained release microspheres of poly-lactide-co-glycolide containing tamoxifen citrate. J. Microencaps. 22, 521-528.
Sener, G., Omurtag, G.Z., Sehirli, O., Tozan, A., Yüksel, M., Ercan, F., Gedik, N., 2006. Protective effects of ginkgo biloba against acetaminophen-induced toxicity in mice. Mol. Cell. Biochem. 283, 39-45.
Sener, G., Toklu, H.Z., Sehirli, A.O., Velioğlu-Oğünç, A., Cetinel, S., Gedik, N., 2006. Protective effects of resveratrol against acetaminophen-induced toxicity in mice. Hepatol. Res. 35, 62-68.
Singer, A.J., Carracio, T.R., Mofenson, H.C., 1995. The temporal profile of increased transaminase levels in patients with acetaminophen-induced liver dysfunction. Ann. Emerg. Med. 26, 49-53.
Slater, T.F., 1984. Free-radical mechanisms in tissue injury. Biochem. J. 222, 1-15.
Soppimath, K.S., Aminabhavi, T.M., Kulkarni, A.R., Rudzinski, W.E., 2001. Biodegradable polymeric nanoparticles as drug delivery devices. J. Control. Release. 70, 1-20.
Stephens, J.W., Khanolkar, M.P., Bain, S.C., 2008. The biological relevance and measurement of plasma markers of oxidative stress in diabetes and cardiovascular disease. Atherosclerosis. (In press)
Tantishaiyakul, V., Kaewnopparat, N., Ingkatawornwong, S., 1999. Properties of solid dispersions of piroxicam in polyvinylpyrrolidone. Int. J. Pharm. 181, 143-151.
Toklu, H.Z., Sehirli, A.O., Velioğlu-Oğünç, A., Cetinel, S., Sener, G., 2006. Acetaminophen-induced toxicity is prevented by beta-D-glucan treatment in mice. Eur. J. Pharmacol. 543, 133-140.
Ubrich, N., Schmidt, C., Bodmeier, R., Hoffman, M., Maincent, P., 2005. Oral evaluation in rabbits of cyclosporin-loaded Eudragit RS or RL nanoparticles. Int. J. Pharm. 288, 169-175.
Venkateswarlu, V., Manjunath, K., 2004. Preparation, characterization and in vitro release kinetics of clozapine solid lipid nanoparticles. J. Control. Release. 95, 627-638.
Vicente-Sánchez, C., Egido, J., Sánchez-González, P.D., Pérez-Barriocanal, F., López-Novoa, J.M., Morales, A.I., 2008. Effect of the flavonoid quercetin on cadmium-induced hepatotoxicity. Food. Chem. Toxicol. 46, 2279-2287.
Wang, S.L., Lin, S.Y., Chen, T.F., Cheng, W.T., 2004. Eudragit E accelerated the diketopiperazine formation of enalapril maleate determined by thermal FTIR microspectroscopic technique. Pharm. Res. 21, 2127-2132.
Watson, D.G., Oliveira, E.J., 1999. Solid-phase extraction and gas chromatography-mass spectrometry determination of kaempferol and quercetin in human urine after consumption of Ginkgo biloba tablets. J. Chromatogr. B. 723, 203-210.
Williams, A.C., Timmins, P., Lu, M., Forbes, R.T., 2005. Disorder and dissolution enhancement: deposition of ibuprofen on to insoluble polymers. Eur J Pharm Sci. 26, 288-294.
Windrum, P., Morris, T.C., Drake, M.B., Niederwieser, D., Ruutu, T., 2005. Variation in dimethyl sulfoxide use in stem cell transplantation: a survey of EBMT centres, Bone. Marrow. Transplant. 36, 601-603.
Wong, S.H., Knight, J.A., Hopfer, S.M., Zaharia, O., Leach, C.N., Sunderman, F.W., 1987. Lipoperoxides in plasma as measured by liquid chromatographic separation of malondialdehyde thiobarbituric acid adduct. Clin. Chem. 33, 214-220.
Wu, T.H., Yen, F.L., Lin, L.T., Tsai, T.R., Lin, C.C., Cham, T.M., 2008. Preparation, physicochemical characterization, and antioxidant effects of quercetin nanoparticles. Int. J. Pharm. 346, 160-168.
Yamamura, S., Gotoh, H., Sakamoto, Y., Momose, Y., 2000. Physicochemical properties of amorphous precipitates of cimetidine-indomethacin binary system. Eur. J. Pharm. Biopharm. 49, 259-265.
Yen, F.L., Wu, T.H., Lin, L.T., Lin, C.C., 2007. Hepatoprotective and antioxidant effects of Cuscuta chinensis against acetaminophen-induced hepatotoxicity in rats. J. Ethnopharmacol. 111, 123-128.
Yen, F.L., Wu, T.Z., Lin, L.T., Cham, T.M., Lin, C.C., 2008. Nanoparticles formulation of Cuscuta chinensis prevents acetaminophen-induced hepatotoxicity in rats. Food. Chem. Toxicol. 46, 1771-1777.
Yu, J.W., Yoon, S.S., Yang, R., 2001. Iron chlorin e6 scavenges hydroxyl radical and protects human endothelial cells against hydrogen peroxide toxicity. Biol. Pharm. Bull. 24, 1053-1059.
Zhang, H., Lu, Y., Zhang, G., Gao, S., Sun, D., Zhong, Y., 2008. Bupivacaine-loaded biodegradable poly(lactic-co-glycolic) acid microspheres I. Optimization of the drug incorporation into the polymer matrix and modelling of drug release. Int J Pharm. 351, 244-249.
Zili, Z., Sfar, S., Fessi, H., 2005. Preparation and characterization of poly-epsilon-caprolactone nanoparticles containing griseofulvin. Int. J. Pharm. 294, 261-267.
Zou, Y., Yang, Y., Li, J., Li, W., Wu, Q., 2006. Prevention of hepatic injury by a traditional Chinese formulation, BJ-JN, in mice treated with Bacille-Calmette-Guérin and lipopolysaccharide. J. Ethnopharmacol. 107, 442-448.
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