Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/14420
標題: 四環黴素及磺胺甲基噁唑在水耕小白菜的藥物動力學:吸收、分布、代謝及排除
The pharmacokinetics of tetracycline and sulfamethoxazole in Brassica chinensis L. grown under hydroponic conditions: the uptake, distribution, metabolism and elimination
作者: 吳郁潔
Wu, Yu-Jie
關鍵字: 四環黴素;pharmacokinetics;磺胺甲基噁唑;小白菜;藥物動力學;tetracycline;sulfamethoxazole
出版社: 獸醫學系暨研究所
引用: 蔡尚光。水耕栽培的經營。淑馨出版社。台北,1997。 Agwuh KN, and MacGowan A. Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines. J Antimicrob Chemother 58: 256-265, 2006. Awad YM, Kim S-C, Abd El-Azeem SAM, Kim K-H, Kim K-R, Kim K, Jeon C, Lee SS, and Ok YS. Veterinary antibiotics contamination in water, sediment, and soil near a swine manure composting facility. Environmental Earth Sciences 2013. Benitz KF, and Diermeier HF. Renal Toxicity of Tetracycline Degradation Products. Exp Biol Med 115: 930-935, 1964. Boonsaner M, and Hawker DW. Investigation of the mechanism of uptake and accumulation of zwitterionic tetracyclines by rice ( Oryza sativa L.). Ecotoxicol Environ Saf 78: 142-147, 2012. Bowman SM, Drzewiecki KE, Mojica ER, Zielinski AM, Siegel A, Aga DS, and Berry JO. Toxicity and reductions in intracellular calcium levels following uptake of a tetracycline antibiotic in Arabidopsis. Environ Sci Technol 45: 8958-8964, 2011. Boxall AB, Johnson P, Smith EJ, Sinclair CJ, Stutt E, and Levy LS. Uptake of veterinary medicines from soils into plants. J Agric Food Chem 54: 2288-2297, 2006. Boxall AB, Blackwell P, Cavallo R, Kay P, and Tolls J. The sorption and transport of a sulphonamide antibiotic in soil systems. Toxicol Lett 131: 19-28, 2002. Burken JG. Uptake and Metabolism of Organic Compounds: Green-Liver Model. Phytoremediation: Transformation and Control of Contaminants 59-84, 2003. Capone DG, Weston DP, Miller V, and Shoemaker C. Antibacterial residues in marine sediments and invertebrates following chemotherapy in aquaculture. Aquaculture 145: 55-75, 1996. Chenxi Wu, Alison L. Spongberg, D. J, Witter, Min Fang, and Czajkowski Kp . Uptake of Pharmaceutical and Personal Care Products by Soybean Plants from Soils Applied with Biosolids and Irrigated with Contaminated Water. Environ Sci Technol 1-5, 2010. Chiou Ct, Guangyao Sheng, and Manes M. A Partition-Limited Model for the Plant Uptake of Organic Contaminants from Soil and Water. American Chemical Society 303: 1437-1444, 2001. Conte S, Stevenson D, Furner I, and Lloyd A. Multiple antibiotic resistance in Arabidopsis is conferred by mutations in a chloroplast-localized transport protein. Plant Physiol 151: 559-573, 2009. Dordas C, Chrispeels MJ, and Brown PH. Permeability and Channel-Mediated Transport of Boric Acid across Membrane Vesicles Isolated from Squash Roots. Plant Physiol 124: 1349-1361, 2000. Farkas MH, Mojica ER, Patel M, Aga DS, and Berry JO. Development of a rapid biolistic assay to determine changes in relative levels of intracellular calcium in leaves following tetracycline uptake by pinto bean plants. Analyst 134: 1594-1600, 2009. Gomez MJ, Petrović M, Fernandez-Alba AR, and Barcelo D. Determination of pharmaceuticals of various therapeutic classes by solid-phase extraction and liquid chromatography–tandem mass spectrometry analysis in hospital effluent wastewaters. J Chromatogr 1114: 224-233, 2006. Grondel J, Nouws J, and Haenen O. Fish and antibiotics: Pharmacokinetics of sulphadimidine in carp (Cyprinus carpio). Vet Immunol Immunopathol 12: 281-286, 1986. Grote M, Schwake-Anduschus C, Michel R, Stevens H, Heyser W, Langenkamper G, Betsche T, and Freitag M. Incorporation of veterinary antibiotics into crops from manured soil. Landbauforschung Volkenrode 57: 25, 2007. Gujarathi NP, and Linden JC. Oxytetracycline inactivation by putative reactive oxygen species released to nutrient medium of Helianthus annuus hairy root cultures. Biotechnol Bioeng 92: 393-402, 2005. Hamscher G, Sczesny S, Hoper H, and Nau H. Determination of Persistent Tetracycline Residues in Soil Fertilized with Liquid Manure by High-Performance Liquid Chromatography with Electrospray Ionization Tandem Mass Spectrometry. American Chemical Society 74: 1509-1518, 2002. Hedrich R. Ion channels in plants. Physiol Rev 92: 1777-1811, 2012. Herklotz PA, Gurung P, Vanden Heuvel B, and Kinney CA. Uptake of human pharmaceuticals by plants grown under hydroponic conditions. Chemosphere 78: 1416-1421, 2010. Hou J, Pan B, Niu X, Chen J, and Xing B. Sulfamethoxazole sorption by sediment fractions in comparison to pyrene and bisphenol A. Environ Pollut 158: 2826-2832, 2010. Hu X, Zhou Q, and Luo Y. Occurrence and source analysis of typical veterinary antibiotics in manure, soil, vegetables and groundwater from organic vegetable bases, northern China. Environ Pollut 158: 2992-2998, 2010. Ji L, Wan Y, Zheng S, and Zhu D. Adsorption of tetracycline and sulfamethoxazole on crop residue-derived ashes: Implication for the relative importance of black carbon to soil sorption. Environ Sci Technol 45: 5580-5586, 2011. Kummerer K, and Henninger A. Promoting resistance by the emission of antibiotics from hospitals and households into effluent. Clin Microbiol Infect 9: 1203-1214, 2003. Kay P, Blackwell PA, and Boxall A. Fate of veterinary antibiotics in a macroporous tile drained clay soil. Environ Toxicol Chem 23: 1136-1144, 2004. Kemper N. Veterinary antibiotics in the aquatic and terrestrial environment. Ecol Indicators 8: 1-13, 2008. Kim H, Hong Y, Park JE, Sharma VK, and Cho SI. Sulfonamides and tetracyclines in livestock wastewater. Chemosphere 91: 888-894, 2013. Kim K-R, Owens G, Kwon S-I, So K-H, Lee D-B, and Ok YS. Occurrence and Environmental Fate of Veterinary Antibiotics in the Terrestrial Environment. Water, Air, Soil Pollut 214: 163-174, 2010. Kong WD, Zhu YG, Liang YC, Zhang J, Smith FA, and Yang M. Uptake of oxytetracycline and its phytotoxicity to alfalfa (Medicago sativa L.). Environ Pollut 147: 187-193, 2007. Kumar K, Gupta S, Baidoo S, Chander Y, and Rosen C. Antibiotic uptake by plants from soil fertilized with animal manure. J Environ Qual 34: 2082-2085, 2005. Lertpaitoonpan W, Ong SK, and Moorman TB. Effect of organic carbon and pH on soil sorption of sulfamethazine. Chemosphere 76: 558-564, 2009. Leal RMP, Alleoni LRF, Tornisielo VL, and Regitano JB. Sorption of fluoroquinolones and sulfonamides in 13 Brazilian soils. Chemosphere 2013. Li Z-J, Xie X-Y, Zhang S-Q, and Liang Y-C. Wheat Growth and Photosynthesis as Affected by Oxytetracycline as a Soil Contaminant. Pedosphere 21: 244-250, 2011. Lin AY-C, Panchangam SC, and Ciou P-S. High levels of perfluorochemicals in Taiwan’s wastewater treatment plants and downstream rivers pose great risk to local aquatic ecosystems. Chemosphere 80: 1167-1174, 2010. Lin AY-C, Yu T-H, and Lin C-F. Pharmaceutical contamination in residential, industrial, and agricultural waste streams: Risk to aqueous environments in Taiwan. Chemosphere 74: 131-141, 2008. Liu F, Ying GG, Tao R, Zhao JL, Yang JF, and Zhao LF. Effects of six selected antibiotics on plant growth and soil microbial and enzymatic activities. Environ Pollut 157: 1636-1642, 2009. Martinez JL. Environmental pollution by antibiotics and by antibiotic resistance determinants. Environ Pollut 157: 2893-2902, 2009. Mathews S, and Reinhold D. Biosolid-borne tetracyclines and sulfonamides in plants. Environmental science and pollution research international 2013. McCoy RE. Use of Tetrracycline atibiotics to control yellows diseases. American Phytopathological Society 3024: 1-4, 1982. Meharg AA, and Jardine L. Arsenite transport into paddy rice ( Oryza sativa ) roots. New Phytol 157: 39-44, 2003. Mette Rabulle, and Niels Henrik Spliid. Sorption and mobility of metronidazole, olaquindox, oxytetracycline and tylosin in soil. Chemosphere 40: 715-722, 2000. Migliore L, Brambilla G, Casoria P, Civitareale C, Cozzolino S, and Gaudio L. Effect of sulphadimethoxine contamination on barley (Hordeum distichum L., Poaceae, Liliopsida). Agriculture Ecosystems AND Environment 60: 121-128, 1996. Muller A, Guan C, Galweiler L, Tanzler P, Huijser P, Marchant A, Parry G, Bennett M, Wisman E, and Palme K. AtPIN2 defines a locus of Arabidopsis for root gravitropism control. EMBO 17: 6903-6911, 1998. Qiao M, Chen W, Su J, Zhang B, and Zhang C. Fate of tetracyclines in swine manure of three selected swine farms in China. JEnvS 24: 1047-1052, 2012. Oka H, Ito Y, Ikai Y, Kagami T, and Harada K-i. Mass spectrometric analysis of tetracycline antibiotics in foods. J Chromatogr 812: 309-319, 1998. Opriş O, Copaciu F, Loredana Soran M, Ristoiu D, Niinemets U, and Copolovici L. Influence of nine antibiotics on key secondary metabolites and physiological characteristics in Triticum aestivum: Leaf volatiles as a promising new tool to assess toxicity. Ecotoxicol Environ Saf 2012. Piotrowicz-Cieslak AI, Adomas B, Nalecz-Jawecki G, and Michalczyk DJ. Phytotoxicity of sulfamethazine soil pollutant to six legume plant species. Journal of toxicology and environmental health Part A 73: 1220-1229, 2010. Samuelsen O, Lunestad B, Husevag B, Holleland T, and Ervik A. Residues of oxolinic acid in wild fauna following medication in fish farms. Dis Aquat Org 12: 111-119, 1992. Sandermann H, Jr. Molecular ecotoxicology of plants. Trends Plant Sci 9: 406-413, 2004. Sanderson H, Laird B, Pope L, Brain R, Wilson C, Johnson D, Bryning G, Peregrine AS, Boxall A, and Solomon K. Assessment of the environmental fate and effects of ivermectin in aquatic mesocosms. Aquat Toxicol 85: 229-240, 2007. Shi J, Yuan X, Chen X, Wu B, Huang Y, and Chen Y. Copper uptake and its effect on metal distribution in root growth zones of Commelina communis revealed by SRXRF. Biol Trace Elem Res 141: 294-304, 2011. Shimizu A, Takada H, Koike T, Takeshita A, Saha M, Rinawati, Nakada N, Murata A, Suzuki T, Suzuki S, Chiem NH, Tuyen BC, Viet PH, Siringan MA, Kwan C, Zakaria MP, and Reungsang A. Ubiquitous occurrence of sulfonamides in tropical Asian waters. Sci Total Environ 452-453: 108-115, 2013. Singh OV, and Jain RK. Phytoremediation of toxic aromatic pollutants from soil. Appl Microbiol Biotechnol 63: 128-135, 2003. Tani F, and Barrington S. Zinc and copper uptake by plants under two transpiration rates. Part II. Buckwheat (Fagopyrum esculentum L.). Environ Pollut 138: 548-558, 2005. Thiele‐Bruhn S. Pharmaceutical antibiotic compounds in soils–a review. J Plant Nutr Soil Sci 166: 145-167, 2003. Tolls J. Sorption of veterinary pharmaceuticals in soils: a review. Environ Sci Technol 35: 3397-3406, 2001. Tomaselli F, Maier A, and Smolle-Juttner F-M. Pharmacokinetics of antibiotics in inflamed and healthy lung tissue. Wien Med Wochenschr 153: 342-344, 2003. Trapp S. Modelling uptake into roots and subsequent translocation of neutral and ionisable organic compounds. Pest Manage Sci 56: 767-778, 2000. Winckler C, and Grafe A. Use of Veterinary Drugs in Intensive Animal Production. Veterinary Drugs 2: 66-70, 2000. Xie X, Zhou Q, Lin D, Guo J, and Bao Y. Toxic effect of tetracycline exposure on growth, antioxidative and genetic indices of wheat (Triticum aestivum L.). Environmental Science and Pollution Research 18: 566-575, 2011. Xu W, Zhang G, Li X, Zou S, Li P, Hu Z, and Li J. Occurrence and elimination of antibiotics at four sewage treatment plants in the Pearl River Delta (PRD), South China. Water Res 41: 4526-4534, 2007. Yannarell AC, and Mackie RI. Environmental impacts of antibiotic use in the animal production industry. Ecology and animal health 2: 228, 2012. Zhang R, Tang J, Li J, Zheng Q, Liu D, Chen Y, Zou Y, Chen X, Luo C, and Zhang G. Antibiotics in the offshore waters of the Bohai Sea and the Yellow Sea in China: occurrence, distribution and ecological risks. Environ Pollut 174: 71-77, 2013. Zurhelle G, Petz M, Mueller-Seitz E, and Siewert E. Metabolites of oxytetracycline, tetracycline, and chlortetracycline and their distribution in egg white, egg yolk, and hen plasma. J Agric Food Chem 48: 6392-6396, 2000. Zuo J, and Chua N-H. Chemical-inducible systems for regulated expression of plant genes. Curr Opin Biotechnol 11: 146-151, 2000.
摘要: 
四環黴素(Tetracycline, TC)和磺胺劑類(Sulfamethoxazole, SMX)為廣泛用於飼料及獸醫治療用途的抗生素類,這些抗生素有高達70 %可以原型或代謝產物形式經由尿液或糞便排出。近年來各國廣泛於土壤及廢水中檢測出μg/mL等級的抗生素濃度,導致環境中的抗生素有可能經由食用植物逆向返回食物鏈或人體的可能性逐漸受到重視。然而,目前抗生素類在植物的藥物動力學(吸收、分佈、代謝及排除)相關研究並不多,有關藥物在植物殘留的資訊亦相對匱乏。因此,本研究擬以水耕小白菜食用植物建立抗生素的完整藥物動力學模式,了解這2類抗生素在蔬菜的移動行為。實驗使用鳳京(Tokita)品種之水耕小白菜,種植於含100 μg/mL TC(或SMX)抗生素之水耕液中共100 mL。以既定間隔採集小白菜之根、莖、葉及培養液測其藥物濃度。樣品經萃取後以HPLC-UV進行偵測。TC及SMX之偵測極限分別為100 ng/mL及50 ng/mL。結果指出,小白菜中TC在根內濃度最高,葉中次之,而莖中最低。且根的濃度在第24小時高達1200 μg/mL且有累積的現象(BAF=21)。TC在葉的濃度在50-60 μg/mL之間,在莖則是10-20 μg/mL。SMX在小白菜各部位的濃度亦為根中濃度最高,莖和葉次之,濃度分別約為30、10和7 μg/mL之間,BAF在根為0.4,莖和葉皆為0.1。三種不同濃度(100、10和1 μg/mL)下比較發現兩種抗生素的吸收和分佈非常相似,證明現在的model也合適用於環境中低濃度抗生素殘留的實況。兩種抗生素在同株每片莖之間和每片葉之間的濃度並沒有顯著差異。在給予TC五天後以HPLC及質譜分析,皆可於葉部發現TC生轉化為Doxycycline,而在給予SMX的組別則在小白菜任何部位皆未檢測到可能的代謝產物。將已經吸收藥物的小白菜,放回到清水中以了解蔬菜排除藥物的能力,結果顯示TC和SMX的排除主要發生在前30分鐘,濃度下降在15~30 %之間,隨後濃度則維持在一穩定狀態。綜合以上結論,TC和SMX在小白菜的藥物動力學表現有著明顯的差異,小白菜吸收TC之能力遠大於吸收SMX,平均每克的菜可以吸收200 μg的TC和6.2 μg的SMX,且極可能具有代謝這些藥物的能力,釋放時則似乎有一個控制的機制或者藥物一旦與蔬菜結合,即不容易脫離。未來,應進一步探討TC和SMX在土耕小白菜的藥物動力學。

Veterinary antibiotics are increasingly being monitored in slurry, soils and surface waters as ground waters have been reported to have antibiotic concentrations ranging from several to hundreds of milligrams per liter. The most commonly detected antibiotics in soil and river in Taiwan are sulfonamides, tetracyclines and lincosamides, the concentrations range between 1570 to 111667 ng/L. Therefore, antibiotics uptake by plants in soil and water matrix becomes not only an environmental but also a human health concern. Our aims are to investigate the pharmacokinetic behaviors (uptake, distribution, metabolism and elimination) of tetracycline (TC) and sulfamethoxazole (SMX) in edible vegetable Brassica Chinensis L.. The vegetable was exposed to 100 μg/mL TC or SMX in cultivation water for up to 24 hrs, drug concentrations in roots, stems and leaves were quantified using optimized HPLC-UV method and the bioaccumulation factors (BAF) in various parts of the vegetable were calculated. The results showed evident differential uptake and distribution of the two antibiotics. TC concentration in the root was as high as 1200 μg/mL, indicating accumulation of the drug in the root (BAF=21 at 24 hr). TC concentration in the leaves was around 50-60 μg/mL while only 10-20 μg/mL was detected in the stem. SMX concentrations in the root and stem/leaves were approximately 30 and 10 μg/mL, respectively, representing BAFs of 0.3 and 0.1. The percentage uptake of TC and SMX by the vegetable were similar at 3 concentration levels (100, 10 and 1 μg/mL) indicating the appropriateness of the current model and the ability of Brassica Chinensis L. to uptake high amount of TC. TC was biotransformed to doxycycline in the leaves on day 5 after exposure while SMX was not metabolized to significant degree. Elimination of TC and SMX from the vegetable back into the cultivation water was noted mainly in the first 0.5 hrs (20-30% reduction) before it reached equilibrium. In conclusion, the pharmacokinetic behaviors of TC and SMX varies in Brassica Chinensis L., it could be significantly uptaken to different parts of the vegetable, being metabolized to different degree and released back to the environment through the root in a controlled manner.
URI: http://hdl.handle.net/11455/14420
其他識別: U0005-3008201312404300
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