微囊藻毒素对滤食性鱼类影响的毒理学实验和野外研究
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摘要
目前,尽管滤食性鱼类经常被暴露在高浓度的微囊藻毒素(MC)中,但MC对这类鱼影响的毒理学研究还很缺乏,滤食性鱼类高强度的抗毒机制也未阐明。本文以我国四大家鱼中的滤食性鱼类鲢、鳙为研究对象,开展了从室内的急性染毒实验到野外的围栏实验,研究MC在鲢、鳙的主要组织器官(肝、肾)中的累积及其引起的细胞和亚细胞结构上的病理变化,血清生化指标的变化和组织匀浆中抗氧化酶系的生化响应,来确定MC对鲢、鳙的毒害作用,以探讨鲢、鳙的抗毒机理及可能的解毒途径,为预防MC对水生动物和人类的危害提供实验依据。主要结果如下:
     1)室内鳙鱼急性毒性实验中,腹腔注射400和1000μg kg-1 bw剂量的MC粗提液,并注射后的1、3、12、24和48h取样,研究MC在肝中的累积和对肝的毒性效应。鳙肝中的MC用HPLC和LC/MS进行定性、定量检测,结果发现低剂量组在注射后12h肝中微囊藻毒素含量最高(2.89μg MCs g-1 DW),高剂量组在注射后3h肝中MC含量即达到最高值(5.43μg MCs g-1 DW),随后MC含量下降,然而肝脏的病理变化在注射后24h内呈时间依赖性的增长,并且肝细胞在低浓度MC作用下主要以细胞凋亡的形式死亡,而高浓度MC作用下主要以细胞坏死的形式死亡。显然,组织损伤相对毒素的累积具滞后性。与病理变化相一致的是,鳙鱼血清中的肝特征酶(ALT、AST、LDH)在注射后开始上升,并在24h达到峰值,之后逐渐恢复到对照组水平。研究中有两个新发现:MC导致的肝脏早期超微结构的变化是使细胞间隙增宽;注射后48h,在两个剂量组均观察到肝组织的恢复现象。另一方面,肝组织中ROS含量,抗氧化酶CAT、SOD,GPX、GR活性和脱毒酶GST活性在处理后均表现出一种先升后降的变化趋势,即在注射后3h逐渐上升达最大值,随后下降到对照组水平,表明CAT、SOD、GPX在清除ROS,抵抗MC的毒性伤害中发挥了关键的作用。尽管两剂量组肝中GSH的含量并未有显著的降低,但GST活性的增加
Little is known on the toxic effects of MC on the phytoplanktivorous fish that are frequently exposed to cyanobacterial toxins because of their habitat and feeding mode. The mechanisms implicated in the high resistance of such fishes to MC have not been elucidated yet. The purposes of this study were to examine, through both acute toxic experiment under laboratory conditions and field investigation in fish pen, the changes of MC concentration, histo- and ultrastructure of liver and kidney and serum biochemical parameters as well as biochemical responses of antioxidant and detoxification systems in the phytoplantivorous silver and bighead carps and to discuss the toxic effects of MC on these fish with comments on the possible mechanisms of high resistance and detoxification capacities in phytoplantivorous fish. The results were summarized as follows:
     1) Bighead carp were injected i.p. with extracted microcystins (mainly MC-RR and–LR) at two doses, 400 and 1000μg kg-1 bw, and the changes in extractable MC in liver, in the histo- and ultra-structure of hepatocytes, and in serum biochemical parameters as well as biochemical responses of antioxidant and detoxification systems were studied at 1, 3, 12, 24 and 48 hr after injection. Quantitative and qualitative determinations of MC in the liver were conducted by HPLC
引文
1. 陈刚,俞顺章,卫国荣,陈公超,徐小英,黄裕华,Harada K I,Ueno Y。肝癌高发区不同饮用水类型中微囊藻毒素含量调查。中华预防医学杂志,1996,30(1):6-9。
    2. 陈家长,胡庚东,张瑞涛。太湖微囊藻对哺乳动物毒性影响的研究。环境污染与防治,1996,18(3):4-5。
    3. 陈家长,胡庚东,张瑞涛。太湖微囊藻对鱼类毒性影响的研究。水产科技情报,1995,22(4):169-171。
    4. 狄留妹。微囊藻毒素对人体健康影响的研究。江苏预防医学,2002,13(3):5-6。
    5. 桂远明,吴垠,祝国芹,沈成刚。几种养殖鱼类越冬生理生化指标的变化—血液指标及代谢率。大连水产学院学报,1994,9(3):15-27。
    6. 何家菀,何振荣,余敏娟。微囊藻质粒与毒性。水生生物学报,1990,14(1):93-94。
    7. 何家菀,李络平,俞家禄。我国产毒微囊藻的新发现韦氏微囊藻及其毒性的初步研究。水生生物学报, 1996,20(2):192-194。
    8. 何家苑,何振荣,郭琼林。有毒铜绿微囊藻对鱼和溞的毒性??科学,1997,9(1):49-56。
    9. 何振荣,俞家禄,何家菀,张甫英,余敏娟。东湖蓝藻水华毒性的研究(II):季节变化及微囊藻的毒性。水生生物学报,1989,13(3):201-209。
    10. 雷腊梅,宋立荣。微囊藻毒素 LR 对小鼠的急性毒性研究。第一军医大学学报,2005,25(5):565-566。
    11. 雷腊梅,宋立荣。微囊藻及其毒素的分子生物学研究进展。自然科学进展,2002,12(4):350-355。
    12. 李效宇,刘永定,宋立荣,雷腊梅,王山杉。微囊藻毒素对大鳞副泥鳅胚胎和幼鱼的毒性效应。水生生物学报,2003,27(3):318-319。
    13. 李效宇,宋立荣,刘永定。微囊藻毒素的产生、检测和毒理学研究。 水生生物学报,1999,23(5):517-523。
    14. 连民,刘颖,俞顺章,陈传炜,周学富,周余春,丁宝国,王如鸿。饮水中微囊藻毒素对人群健康影响的横断面研究。中华流行病学杂志,2000,21(6):440。
    15. 林玉娣,俞顺章,徐明,杨坚波,陈艳,胡磊,沈炜。无锡太湖水域藻类毒素污染与人群健康关系研究。上海预防医学杂志,2003,15(9),435-437。
    16. 刘惠,王晓蓉,张景飞,沈骅。铜及其配合物对鲫鱼肝脏谷胱甘肽的影响。南京大学学报,2004,40(3):356-361。
    17. 刘建康,谢平。用鲢鳙直接控制微囊藻水华的围隔试验和湖泊实践。生态科学,2003,22(3):193-196。
    18. 米瑞芙,陶炳春,王晓梅,谢宝华。鲢鱼败血症血液生理生化指标的变化。淡水渔业,1993,23(4):16-19。
    19. 穆丽娜,陈传炜,俞顺章,刘建玲,吴亚英,朱文昌。太湖水体微囊藻毒素含量调查及处理方法研究。中国公共卫生,2000,16(9):803-804。
    20. 施玮,朱惠刚。微囊藻毒素毒理学研究综述。上海环境科学,2000,
    19(2):82-85。
    21. 宋立荣,雷腊梅,何振荣,刘永定。 滇池水华蓝藻铜绿微囊藻和绿色微囊藻的生长生理特性及毒素分析。水生生物学报,1999,23(5):402-407。
    22. 隋海霞,陈艳,严卫星,徐海滨。淡水湖泊中微囊藻毒素的污染。中国食品卫生杂志,2004,16(2):112-114。
    23. 孙露,沈萍萍,周莹,华子春。太湖微囊藻毒素对小鼠免疫功能的影响。中国药理学与毒理学杂志,2002,16(3):226-230。
    24. 王红兵,刘世杰。微囊藻毒素、佛波酯和苯巴比妥钠对细胞间隙通讯和细胞内Ca2+浓度的影响。北京大学学报(医学版),1998,30(6):121-125。
    25. 王红兵,宋伟民,朱惠刚。上海淀山湖、黄浦江水系浮游藻类及藻类毒素的动态研究。环境与健康杂志,1995a,12(5):1996-1999。
    26. 王红兵,朱惠刚。微囊藻粗毒素对大鼠肝细胞 DNA 合成和损伤的影响。上海环境科学,1995b,14:34-36。
    27. 武忠弼主编。超微病理诊断学。上海:上海科学技术出版社,2003, pp:279-280。
    28. 夏世钧,吴中亮。分子毒理学基础。武汉,湖北科学技术出版社,2000。
    29. 谢平著。鲢、鳙与藻类水华控制。第一章 鲢鳙的自然分布及向国外的引种历史。北京:科学出版社,2003,pp:1-12。
    30. 徐海滨,孙明,隋海霞,李建平,严卫星。江西鄱阳湖微囊藻毒素污染及其在鱼体内的动态研究。卫生研究,2003, 32(3):192-194。
    31. 徐镜波,袁晓凡,朗佩珍。过氧化氢酶活性及活性抑制的紫外分光光度测定。环境化学,1997,16(1):73-76。
    32. 徐立红,陈国胜,陈加平,许建明,张甬元。微囊藻毒素对鱼肝的毒性效应。水生生物学报,1998,22(4):378-379。
    33. 徐立红,张甬元。微囊藻分子致毒机理研究近况。水生生物学报,1993,17(4):365-375。
    34. 徐立红,周炳升,张甬元,徐盈,原田健一。微囊藻毒素环境行为的初步研究。水生生物学报,1997,21(1):85-89。
    35. 许秋瑾,高光,陈伟民。太湖微囊藻毒素年变化及其与浮游生物的关系。中国环境科学,2005,25(1):28-31。
    36. 杨清心。太湖水华成因及控制途径初探。湖泊科学,1996,8(1):67-74。
    37. 俞家禄,陈明惠,林坤二,余敏娟。武汉东湖蓝藻水华毒性的研究(I):淡水蓝藻水华毒性的检测。水生生物学报,1987,11(2):212-218。
    38. 翟良安,倪朝辉,叶雄平等。“浸螺杀”对鲤鱼生化和血液指标影响的研究。淡水渔业,1992(4):24-26。
    39. 张铣,刘毓谷主编。毒理学。北京:北京医科大学,中国协和医科大学联合出版社,1997。
    40. 张占英,连民,刘颖,卫国,俞顺章,张幼辰,陈传炜,康苏亚。微囊藻毒素 LR 对胎鼠的致畸和损伤作用。中华医学杂志,2002,82(5):345-347。
    41. 章宗涉,黄祥飞。淡水浮游生物研究方法。北京:科学出版社,1991。
    42. 赵会宏,刘志强,贝念湘,赵红琼。几种不同属性鱼类血液流变学性质的比较研究。新疆农业大学学报,2000,23(4):1-8。
    43. 周炳升,徐立红,张甬元,徐盈。微囊藻毒素 LR 对草鱼肝脏超微结构影响的研究。水生生物学报,1998,22(1):90-92。
    44. Aebi, H. Catalase in vitro. In: Methods in Enzymology, Vol. 105 (Packer L, editor). Orlando: Academic Press, 1984. pp 121-126.
    45. Andersen, R.J., Luu, H.A., Chen, D.Z.X., Holmes, C.F.B., Kent, M.L., Le Blanc, M., Taylor, F.J.R., Williams, D.E. Chemical and biological evidence links microcystins to salmon ‘net-pen liver disease’. Toxicon, 1993, 31:1315-1323.
    46. Anthony, R.A., Wayne, W.C. Evidence that microcystin is a thiotemplate product. J Phycol, 1996, 32:591-597.
    47. Arteel, G.E., Sies, H. The biochemistry of selenium and the glutathione system. Environ Toxicol Phar, 2001, 10:153-158.
    48. Baganz, M., Staaks, G., Steinberg, C. Impact of the cyanobacteria toxin, microcystin-LR on behavior of zebrafish, Danio rerio. Wat Res, 1998, 32(3):948-952.
    49. Bagu, J.R, Sykes, B.D., Craig, M.M., Holmes, C.F.B. A molecular basis for different interactions of marine toxins with protein phosphatase-1, molecular models for bound motuporin, microcystins, okadaic acid and calyculin A. J Biol Chem, 1997, 272:5087-5097.
    50. Bayer, W.F., Fridovich, J.L. Assaying for superoxide dismutase activity: some large consequences of minor changes in conditions. Anal Biochem, 1987, 161:559-566.
    51. Beattie, K. Application and performance assessment of an commercially-available ELISA pit for microcystis. 4th International conference of Toxic cyanobacteria, 1998, p 18.
    52. Bogé, G., Leydet, M., Houvet, D. The effects of hexavalent chromium on the activity of alkaline phosphatase in the intestines of rainbow trout (Oncorhynchus myhiss). Aquatic Toxicol, 1992, 23:247-260.
    53. Botes, D.P., Viljoen, C.C., Kruger, H., Wessels, P.L., Williams, D.H. Configuration assignments of the amino acid residues and the presence of N-methyldehydroalanine in toxins from the blue-green algae, Microcystis aeruginosa. Toxicon, 1982, 20:1037-1042.
    54. Braford, M.M. A rapid and sensitive method for the quantification of microgram quantities of protein using the principle of protein dye-binding. Anal Biochem, 1976, 72:248-254.
    55. Braunbeck, T. Cytological alterations in fish hepatocytes following in vivo and in vitro sublethal exposure to xenobiotics-structural biomarkers of environmental contamination. In: Braunbeck, T., Hinton, D.E., Streit, B. (Eds), Fish Ecotoxicology, Birkh?user, Basel, 1998,pp 61-40.
    56. Brooks, W.P., Winslow, G.M. Distribution of microcystis aeruginose peptide toxin and interaction with hepatic microsomes in mice. Pharmacol Toxicol, 1987, 60:187-191.
    57. Bury, N.R., McGeer, J.C., Eddy, F.B., Codd, G.A. Liver damage in brown trout, Salmo trutta L., and rainbow trout, Oncorhynchus mykiss (Walbaum), following admistration of the cyanobacterial hepatotoxin microcystin-LR via the dorsal aorta. J Fish Dis, 1997, 20:209-215.
    58. Carbis, C.R., Rawlin, G.T., Grant, P., Mitchell, G.F., Anderson, J.W., McCauley, I. A study of feral carp, Cyprinus carpio L. exposed to Microcystis aeruginosa at Lake Mokoan, Australia, and possible implications for fish health. J Fish Dis, 1997, 20:81-91.
    59. Carbis, C.R., Rawlin, G.T., Mitchell, G.F., Anderson, J.W., McCauley, I. The histopathology of carp, Cyprinus carpio L., exposed to microcystins by gavage, immersion and intraperitoneal administration. J Fish Dis, 1996, 19:199-207.
    60. Carbis, C.R., Simons, J.A., Mitchell, G.F., Anderson, J.W., McCauley, I. A biochemical profile for predicting the chronic exposure of sheep to microcystis aeruginosa, a hepatotoxic specie of blue-green alga. Res Vet Sci, 1994, 57(3):310-316.
    61. Carlberg, I., Mannervik, B. Purification and characterization of the flavoenzyme glutathione reductase from rat liver. J Biol Chem, 1975, 250:5475-5480.
    62. Carmichael, W.W. The toxins of cyanobacteria. Sci Am, 1994, 270:64-72.
    63. Carmichael, W.W. Toxic Microcystis and the Environment. In: Watanabe, M.F. (Ed). Toxic Microcystis. New York: CRC Press, 1996, pp 1-12.
    64. Carmichael, W.W., Beasley, V.R., Bunner, D.L., Naming of cyclic heptapeptide toxins of cyanobacteria (blue-green algae). Toxicon, 1998, 26:1213-1217
    65. Chorus, I., Bartram, J. Toxic cyanobacteria in water. A guide to public health consequences, monitoring and management. London: E & FN spon on behalf of WHO, 1999, pp:211-256.
    66. Codd, G.A, Morrison, L.F., Metcalf, J.S. Cyanobacterial toxins: risk management for health protection. Toxicol Appl Pharm, 2005, 203(3):264-272.
    67. Cousins, I.T., Bealing, D.J., James, H.A., Sutton, A. Biodegradation of microcystin-LR by indigenous mixed bacterial populations. Water Res, 1996, 30:481-484.
    68. Creasia, D.A. Acute inhalation toxicity of microcystin-LR with mice.Toxicon, 1990, 28:605.
    69. Dabholkar, A.S., Carmichael, W.W. Ultrastructural changes in the mouse liver induced by hepatotoxin from the freshwater cyanobacterium Microcystis aeruginosa strain 7820. Toxicon, 1987, 25(3):285-292.
    70. Dahlem, A.M. Structure/toxicity relationships and fate of low molecular weight peptide toxins from cyanobacterial. Ph. D. Thesis, University of Illinois, 1989:135-148.
    71. Dawson, R.M. The toxicology of microcystin. Toxicon, 1998, 36:953-962.
    72. Dewan, S., Wahab, M.A., Beveridge, M.C.M., Rahman, M.H., Sarkar, B.K. Food selection, electivity and dietary overlap among planktivorous Chinese and Indian major carp fry and fingerlings grown in extensively managed, rain-fed ponds in Bangladesh. Aquacult Fish Management, 1991, 22:277-294.
    73. Ding, W.X, Shen, H.M., Zhu, H.G., Ong, C.N. Genotoxicity of microcystic cyanobacteria extract of a water source in China. Mut Res, 1999, 442:69-77.
    74. Ding, W.X., Ong, C.N. Role of oxidative stress and mitochondrial changes in cyanobacteria-induced apoptosis and hepatotoxicity. FEMS Microbiol Lett, 2003, 220:1-7.
    75. Ding, W.X., Shen, H.M., Ong, C.N. Microcystic cyanobacteria extract induces cytoskeletal disruption and intracellular glutathione alteration in hepatocytes. Environ Health Perspect, 2000, 108:605-609.
    76. Ding, W.X., Shen, H.M., Zhu, H.G., Ong, C.N. Studies on oxidative damage induced by cyanobacteria extract in primary cultured rat hepatocytes. Environ Res, 1998, 78:12-18.
    77. Dittmann, E., Neilan, B.A., Erhard, M., von D?hren, H., B?rner, T. Insertional mutagenesis of a peptide synthetase gene that is responsiblefor hepatotoxin production in the cyanobactrium Microcystis aeruginosa PCC7806. Mol Microbiol, 1997, 26:779-787.
    78. Drotar, A., Phelps, P., Fall, R. Evidence for glutathione peroxidase activities in cultured plant cells. Plant Sci, 1985, 42: 35-40.
    79. Eriksson, J.E., Toivola, D., Meriluoto, J.A.O., Karaki, H., Han, Y., Hartshorne, D. Hepatocyte deformation induced by cyanobacterial toxins reflects inhibition of protein phosphatases. Biochem Biophys Res Commun, 1990, 173:1347-1353.
    80. Falconer, I.R. Mechanism of toxicity of cyclic peptide toxins from blue-green algae. In: Falconer, I.R. (Ed). Algal Toxins in Seafood and Drinking Water. London: Academic Press, 1993, pp 165-176.
    81. Falconer, I.R. Oral toxicity of a bloom of the cyanobacterium Microcystis aeruginosa administion to mice over periods up to 1 year. J Toxicol Environ Health, 1998, 24:291-305.
    82. Falconer, I.R., Hardy, S.J., Humpage, A.R., Froscio, S.M., Tozer, G.J., Hawkins, P.R. Hepatic and renal toxicity of the blue-green alga (cyanobacterium) clylindrospermopsis raciborslii in male swiss albino mice. Environ Toxicol, 1999, 14:143-150.
    83. Falconer, I.R., Yeung, D.S.K. Cytoskeletal changes in hepatocytes induced by Microcystis toxins and their relation to hyperphosphorylation of cell proteins. Chem Biol Interaction, 1992, 81:181-196.
    84. FAO, 1991. Fishery Statistics, Catches and Landing, FAO Yearbook. Food and Agriculture Organization of the United Nations, Rome.
    85. Filho, W. Fish antioxidant defenses. A comparative approach. Braz J Med Bio Res, 1996, 29:1735-1742.
    86. Fischer, W.J., Dietrich, D.R. Pathological and biochemical characterization of microcystin-induced hepatopancreas and kidney damage in carp (Cyprinus carpio). Toxicol Appl Pharmacol, 2000,164:73-81.
    87. Fischer, W.J., Hitzfeld, B.C., Tencalla, F., Eriksson, J.E., Mikhailov, A., Dietrich, D.R. Microcystin-LR toxicodynamics, induced pathology, and immuohistochemical location in livers of blue-green algae exposed rainbow trout (Oncorhynchus mykiss). Toxicol Sci, 2000, 54:365-373.
    88. Folmar, L.G. Effects of chemical contaminants on blood chemistry of teleost fish a bibliography and synopsis of selected effects. Environ Toxicol Chem, 1993, 12:337-375.
    89. Francis, G. Poisonous Australian Lake. Nature (London), 1878, 18:11-12.
    90. Garcia, B.O. Toxicity of the cyanobacterium, Microcystis aeruginosa strain 7820 to trout and tilapia: a clinical and histopathological study. M Sc Thesis, University of Stirling, Stirling, 1989.
    91. Gehringer, M.M., Shephard, E.G., Downing, T.G., Wiegand, C., Neilan, B.A. An investigation into the detoxification of microcysin-LR by the glutathione pathway in Balb/c mice. Int J Biochem Cell Biol, 2004, 36:931-941.
    92. Griffith, O. Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem, 1980, 106:207-212.
    93. Gupta, N., Pant, S.C., Vijayaraghavan, R., Lakshmana Rao, P.V. Comparative toxicity evaluation of cyanobacterial cyclic peptide toxin microcystin variants (LR, RR, YR) in mice. Toxicology, 2003, 188:285-296.
    94. Guzman, R.E., Solter, P.F. Hepatic oxidative stress following prolonged sublethal microcystin-LR exposure. Toxicol Pathol, 1999, 27:582-588.
    95. Habig, W.H., Pabst, M.J., Jakoby, W.B. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem,1974, 249:7130-7139.
    96. Harada, K.I. Chemistry and Detection of Microcystins. In: Watanabe, M.F., et al., (Eds), Toxic Microcystis. New York: CRC press, 1996a, pp 103-148.
    97. Harada, K.I., Murata, H., Qiang, Z., Suzuki, M., Kondo, F. Mass spectrometric screening method for microcystins in cyanobacteria. Toxicon, 1996b, 34:701-702.
    98. Harada, K.I., Suzuki, M., Dahlem, A.M., Beasley, V.R. Carmichael, W.W., Rinehart, K.L. Improved method for purification of toxic peptides produced by cyanobacteria. Toxicon, 1988, 26:433-439.
    99. Hermansky, S.J., Stohs, S, J., Eldeen, Z.M., Roche, V.F., Mereish, K.A. Evaluation of potential chemoprotectants against microcystin-LR hepatotoxicity in mice. J Appl Toxicol, 1991, 11:65-73.
    100. Hilmy, A.M., Shabana, M.B., Daabees, A.Y. Effects of cadmium toxicity upon the in vivo and in vitro activity of proteins and five enzymes in blood serum and tissue homogenates of Mugil cephalus. Comp Biochem Physiol C, 1985, 81:145-153.
    101. Hui, T.C., Wang, J.G., Zhu, Y.M. Effect of Cd on hepatic GSH metabolism in T. nilotics. Journal of Zhejiang University (Agric. & Life Sci.), 2001, 27:575-578. (in Chinese).
    102. Husain, K., Scott, B.R., Reddy, S.K., Somani, S.M. Chronic ethanol and nicotine interaction on rat tissue antioxidant defense system. Alcohol, 2001, 25:89-97.
    103. Hyenstrand, P., Blomqvist, P., Petterson, A. Factors determining cyanobacterial success in aquatic systems – a literature review. Arch Hydrobiol Spec Issues Adv Limnol, 1998, 15:41-62.
    104. Inokuchi, S., Sakai, T., Skirato, I., Tomino, Y., Koide, H. Ultrastructural changes in glomerular epithelial cells in acute puromycin aminonucleoside nephrosis: a study by high-resolutionscanning electron microscopy. Virchows Arch, 1993, 423: 111-119.
    105. Ito, E., Kondo, F., Terao, K., Harada, K.I. Neoplastic nodular formation in mouse liver induced by repeated intraperitoneal injections of microcystin-LR. Toxicon, 1997, 35(9):1453-1457.
    106. Jenkins, R.R., Goldfarb, A. Introduction: oxidant stress, aging and exercise. Med Sci Sports Exerc, 1993, 25:210-212.
    107. Jos, á., Pichardo, S., Prieto, A.I., Repetto, G., Vázquez, C.M., Moreno, I., Cameán, A.M. Toxic cyanobacterial cells containing microcystins induce oxidative stress in exposed tilapia fish (Oreochromis sp.) under laboratory conditions. Aquat Toxicol, 2005, 72:261-271.
    108. Kerr, J.F.R., Wyllie, A.H., Currie, A.R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer, 1972, 26:239-157.
    109. Keshavanath, P., Beveridge, M.C.M., Baird, D.J., Lawton, L.A., Nimmo, A., Codd, G.A. The functional grazing response of a phytoplanktivorous fish Oreochromis niloticus to mixtures of toxic and non-toxic strains of the cyanobacterium Microcystis aeruginosa. J Fish Biol, 1994, 45:123-129.
    110. Khan, S.A., Wickstrom, M.L., Haschek-Hock, W.M., Schaeffer, D.J., Ghosh, S., Beasley, B.R. Microcystin-LR-induced alterations in the cytoskeleton of cultured hepatocytes, kidney cells, and fibroblasts. Nat. Toxins, 1996, 4:217-220.
    111. Kleikauf, H., von D?hren, H. A non-ribosomal system of peptide biosynthesis. Eur J Biochem, 1996, 236:335-351.
    112. Kondo, F., Ikai, Y., Oka, H., Okumura, M., Ishikawa, N., Harada, K.I., Matsuura, K., Murata, H., Suzuki, M. Formation, characterization and toxicity of the glutathione and cysteine conjugates of toxic heptapeptide microcystin. Chem Res Toxicol, 1992, 5:591-596.
    113. Kondo, F., Matsumoto, H., Yamada, S., Ishikawa, N., Ito, E., Nagata,S., Ueno, Y., Suzuki, M., Harada, K. Detection and identification of metabolites of microcystins formed in vivo in mouse and rat livers. Chem Res Toxicol, 1996, 9:1355-1359.
    114. Kotak, B.J., Semalulu, S., Friytz, D.L., Prepas, E.E., Hrudey, S.E., Coppock, R.W. Hepatic and renal pathology of intraperitoneally administered microcystin-LR in rainbow trout (Oncorhynchus mykiss). Toxicon, 1996, 34:517-525.
    115. Lambert, T.W., Holmes, C.F.B., Hrudey, S.E. Microcystin class of toxins: health effects and safety of drinking water supplies. Environ Rev, 1994, 26:167-186.
    116. LeClaire, R.D., Parker, G.W., Franz, D.R. Hemodynamic and calorimetric changes induced by microcystin-LR in the rat. J Appl Toxicol, 1995, 15:303-311.
    117. Lee, S., Jang, M.H, Kim, H.S., Yoon, B.D., Oh, H.M. Variation of microcystin content of Microcystis aeruginosa relative to N:P ratio and growth stage. J Appl Microbiol, 2000, 89: 323-329.
    118. Li, X.Y., Chung, I.K., Kim, J.I., Lee, J.A. Subchronic oral toxicity of microcystin in common carp (Cyprinus carpio L.) exposed to Microcystis under laboratory conditions. Toxicon, 2004, 44:821-827.
    119. Li, X.Y., Liu, Y.D., Song, L.R. Cytological alterations in isolated hepatocytes from common carp (Cyprinus carpio L.) exposed to microcystin-LR. Environ Toxicol, 2001, 16:517-522.
    120. Li, X.Y., Liu, Y.D., Song, L.R., Liu, J. Responses of antioxidant systems in the hepatocytes of common carp (Cyprinus carpio L.) to the toxicity of microcystin-LR. Toxicon, 2003, 42:85-89.
    121. Liang, Y., Melack, J.M., Wang, J. Primary production and fish yields in Chinese ponds and lakes. Trans Am Fish Soc, 1981, 110:346-350.
    122. Lock, R.A.C., Balm, P.H.M. Wendelaar, B.S.E. Adapatation of fresh water fish to toxicants: stress mechanism indused by branchialmalfunction. In: Muller, R. & Lloyd, R., (Eds), Fishing, Sublethal and chronic effects of pollutants on fresh water fish. Oxford: News Books. 1994, pp 124-134.
    123. Maagd, P.G., Hendriks, A.J., Seinen, W., Sijm, D.T.H.M. pH-Dependent hydrophobicity of the cyanobacteria toxin microcystin-LR. Wat Res, 1999, 33(5):677-680.
    124. Magalh?es, V.F., Marinho, M.M., Domingos, P., Oliveira, A.C., Costa, S.M., Azevedo, L.O., Azevedo, S.M.F.O. Microcystins (cyanobacteria hepatotoxins) bioaccumulation in fish and crustaceans from Sepetiba Bay (Brasil, RJ). Toxicon, 2003, 42:289-295.
    125. Magalh?es, V.F., Soares, P.M., Azevedo, S.M.F.O. Microcystin contamination in fish from the Jacarepaguá Lagoon (Rio de Janeiro, Brazil): ecological implication and human health rish. Toxicon, 2001, 39:1077-1108.
    126. Malbrouck, C., Trausch, G., Devos, P., Kestemont, P. Hepatic accumulation and effects of microcystin-LR on juvenile goldfish Carassius auratus L. Comp Biochem Physiol C, 2003, 135:39-48.
    127. Malyarevskaya A. Influence of anthropogenic eutrophication: effects on fish in the form of blue-green algae mass development. Archiv fur hydrobiologie, 1983, 97(4):417-424.
    128. Matsunaga, H., Harada, K.I., Senma, M., Ito, Y., Yasuda, N., Ushida, S., Kimura, Y. Possible cause of unnatural mass death of wild birds in pond in Nishinomiya, Japan: sudden appearance of toxic cyanobacteria. Nat Toxins, 1999, 7(2):81-84.
    129. McDermott, C.M., Nho, C.W., Howard, W., Holton, B. The cyanobacterial toxin, microcystin-LR can induce apoptosis in a variety of cell types. Toxicon, 1998, 36:1981-1996.
    130. Meiβner, K., Dittmann, E., Borner, T. Toxic and non-toxic strains of the cyanobacterium Microcystis aeruginosa contain sequenceshomologous to peptide synthetase genes. FEMS Microbiol Lett, 1996, 135:295-303.
    131. Milutinovi?, A., Sedmak, B., Horvat-?nidar?i?, I., ?uput, D. Renal injuries induced by chronic intoxication with microcystins. Cell Mol Biol Lett, 2002, 7(1):139-141.
    132. Miura, G.A., Robinson, N.A., Geisbert, T.W., Bostian, K.A., White, J.D., Pace, J.G.. Comparison of in vivo and in vitro toxic effects of microcystin-LR in fasted rats. Toxicon, 1989, 27(11):1229-1240.
    133. Miura, G.A., Robinson, N.A., Lawrence, W.B., Pace, J.G. Hepatotoxicity of microcystin-LR in fed and fasted rats. Toxicon, 1991, 29(3):337-346.
    134. Mohamed, Z.A., Carmichael, W.W., Hussein, A.A. Estimation of microcystins in the freshwater fish Oreochromis niloticus in an Egyptian fish farm containing a Microcystis bloom. Environ Toxicol, 2003, 18:137-141.
    135. Nishiwaki-Matsushima, R., Ohta, T., Nishiwaki, S., Suganuma, M., Kohyama, K., Ishiwaka, T., Carmichael, W.W, Fujiki, H. Liver tumor promotion by the cyanobacterial cyclic peptide toxin microcystin-LR. J Cancer Res Clin Oncol, 1992, 118:420-424.
    136. Nizan, S., Dimentman, C., Shilo, M. Acute toxic effects of the cyanobacterium aeruginosa on Daphnia magna. Limnol Oceanogr, 1986, 31(3):497-502.
    137. Nobre, A.C., Jorge, A.C., Menezes, D.B., Fonteles, M.C., Monteiro, H.S. Effects of microcystin-LR in isolated perfused rat kidney. Braz J Med Biol Res, 1999, 32(8):985-988.
    138. Northcott, M.E., Beveridge, M.C.M., Ross, L.G. A laboratory investigation of the filtration and ingestion rates of the tilapia Oreochromis niloticus, feeding on two species of blue-green algae. Envir Biol Fishes, 1991, 31:75-85.
    139. Opuszynski, K., Shireman, J.V. Merbivorous Fishes-Culture and use for weed management. Florida: CRC press,1995.
    140. Orr, P.T., Jones, G.J. Relation ship between microcystin production and cell division rates in nitrogen-limited Microcystis aeruginosa cultures. Limnel Oceanogr, 1998, 43(7):1604-1614.
    141. ?zcan Oruc, E., üner, N. Effects of azinphosmethyl on some biochemical parameters in blood, muscle, and liver tissues of Cyprinus carpio (L.). Pestic Biochem Phys, 1998, 62:65-71.
    142. Packer, J.E. Oxidative stress, antioxidants, aging and disease. In: Gulter, R.G., Packer, L.B., Eratum, J., Mori, A. (Eds), Oxidtive stress and Aging. Birkhauser Verlag, Basle, 1995, pp 152-163.
    143. Paerl, H.W. A comparison of cyanobacterial bloom dynamics in freshwater, estuarine and marine environments. Phycologia, 1996, 35:25-35.
    144. Park, H.D., Namikoshi, M., Brittain, S.M., Carmichael, W.W., Murphy, T. [D-Leul]microcystin-LR, a new microcystin isolated from waterbloom in Canadian prairie lake. Toxicon, 2001, 39:855-862
    145. Pastore, A., Federici, G., Bertini, E., Piemonte, F. Analysis of glutathione: implication in redox and detoxification. Clinica Chimica Acta, 2003, 333:19-39.
    146. Penaloza, R., Rojas, M., Vila, I., Zambrano, F. Toxicity of a soluble peptide from Microcystis sp. To zooplankton and fish. Freshwat Biol, 1990, 24:233-240.
    147. Pflugmacher, S. Promotion of oxidative stress in the aquatic macrophyte Ceratophyllum demersum during biotransformation of the cyanobacterial toxin microcystin-LR. Aquat Toxicol, 2004, 70:169-178.
    148. Pflugmacher, S., Wiegand, C., Oberemm, A., Beattie, K.A., Krause, E., Codd, G.A., Steinberg, C.E.W. Identification of an enzymaticallyformed glutathione conjugate of the cyanobacterial hepatotoxin microcystin-LR: the first step of detoxication. Biochim Biophys Acta, 1998, 1425:527-533.
    149. Phillips, M.J., Roberts, R.J., Stewart, J.A. The toxicity of the cyanobacterium Microcystis aeruginosa to rainbow trout, Salmo gairdneri. J Fish Dis, 1985, 8:339-344.
    150. Pietsch, C., Wiegan, C., Ame, M.V., Nicklisch, A., Wunderlin, D., Pflugmacher, S. The effects of a cyanobacterial crude extract on different aquatic organism: evidence for cyanobacterial toxin modulating factors. Environ Toxicol, 2001, 16:535-542.
    151. Pinho, G.L.L., Rosa, C.M.D., Yunes, J.S., Luquet, C.M., Bianchini, A., Monserrat, J.M. Toxic effects of microcystins in the hepatopancreas of the estuarine crab Chasmagnathus granulatus (Decapoda, Grapsidae). Comp Biochem Physiol C, 2003, 135:459-468.
    152. Poon, G.K., Griggs, L.J., Edwards, C., Beattie, K.A., Codd, G.A. Liquid chromatography-electrospray ionization-mass spectrometry of cyanobacterial toxin. J Chromatorgr, 1993, 628:215.
    153. Pouria, S., de Andrade, A., Barbosa, J., Cavalcanti, R.J., Barreto, V.T.S., Ward, C.J., Preiser, W., Poon, G.K., Neild, G.H., Codd, G.A. Fatal microcystin intoxication in haemodialysis unit in Caruaru, Brazil. The Lancet, 1998, 352:21-26.
    154. Puschner, B., Galey, F.D., Johnson, B., Dickie, C.W., Vondy, M., Francis, T., Holstege, D.M. Blue-green algae toxicosis in cattle. J Am Vet Med Assoc, 1998, 213(11):1605-1607.
    155. R?bergh, C.M.I., Bylund, G., Eriksson, J.E. Histopathological effects of microcystin-LR, a cyclic peptide toxin from the cyanobacterium (blue-green algae) Microcystis aeruginosa, on common carp (Cyprinus carpio L.). Aquat Toxicol, 1991, 20:131-146.
    156. Richard, J.W., Pleter, G.T. Environmental factors affecting theproduction of peptide toxins in floating scums of the cyanobacterium Microcystis aeruginosa in a hypertrophic African reservoir. Environ Sci Technol, 1990, 24:1413-1418.
    157. Rivasseau, C., Martins, S., Hennion, M.-C. Determination of some physiochemical parameters of microcystins (cyanobacterial toxins) and trace level analysis in environmental samples using liquid chromatography. J Chromatogr, 1998, 799(1-2):155-169.
    158. Robinson, N.A., Pace, J.G., Matson, C.F., Miura, G.A., Lawrence, W.B. Tissue distribution, excretion and hepatic biotransformation of microcystin-LR in mice. J Pharmacol Exp Ther, 1991, 256(1):176-182.
    159. Runnegar, M.T.C., Berndt, N., Kong, S.-M., Lee, E.Y.C., Zhang, L. In vivo and in vitro binding of microcystin to protein phosphatases 1 and 2A. Biochem Biophys Res Commun, 1995, 216:162-169.
    160. Sahin, A., Tencalla, F.G., Dietrich, D.R., Naegeli, H. Biliary excretion of biochemically active cyanobacteria (blue-green algae) Hepatotoxins in fish. Toxicology, 1996, 106:123-130.
    161. Sano, T., Nohara, F., Shiraishi, F., Kaya, K. A method for micro-detection of microcystin content in waterbloom of cyanobacteria (blue-green algae). Int J Environ Anal Chem, 1992, 49:163-170.
    162. Sekijima, M., Tsutsumi, T., Yoshida, T., Harada, T., Tashiro, F., Chen, G., Yu, S.Z, Ueno, Y. Enhancement of glutathione S-transferase placental-form positive liver cell foci development by microcystin-LR in aflatoxin B1-initiated rats. Carcinogenesis, 1999, 20(1):161-165.
    163. Shen, P.P., Shi, Q., Hua, Z.C., Kong, F.X., Wang, Z.G., Zhuang, S.X., Chen, D.C. Analysis of microcystins in cyanobacteria blooms and surface water samples from Meiliang Bay, Taihu Lake, China. Environ Inter, 2003, 29:641-647.
    164. Sivonen, K. Effects of light temperature, nitrate, orthophosphate, and bacteria on growth of and hepatotoxin production by Oscillatoriaagardhii strains. Appl Environ Microbil, 1990, 56:2658-2666.
    165. Slauson, D.O., Cooper, B.J. 1982. Mechanism of Disease: A textbook of comparative general pathology. Williams and Wilkins, Baltimore, MD.
    166. Solter, P.F., Wollenberg, G.K., Huang, X., Chu, F.S., Runnegar, M.T. Prolonged sublethal exposure to the protein phosphatase inhibitor microcystin-LR results in multiple dose-dependent hepatotoxic effects. Toxicol Sci, 1998, 44:87-96.
    167. Song, L., Sano, T., Li, R., Watanabe, M.M., Liu, Y., Kaya. Microcystin production of Microcystis viridis (cyanobacteria) under different culture conditions. Phycol Res, 1998, 46:19-23.
    168. Stein, J.E., Collier, T.K., Reichert, W.L., Casillas, E., Hom, T., Varanasi, U. Bioindicators of contaminant exposure and sublethal effects: studies with benthic fish in Puget sound, Washinton. Environ Toxicol Chem, 1992, 11:701-714.
    169. Stotts, R.R., Namikoshi, M., Haschek, W.M., Rinehart, K.L., Carmichael, W.W., Dahlem, A.M., Beasley, V.R. Structural modifications imparting reduced toxicity in Microcystins from Microcystis Spp. Toxicon, 1993, 31:783-789.
    170. Suchy, F.J. Hepatocellular transport of bile acids. Semin Liver Dis, 1993, 13(3):235-247.
    171. Takenaka, S. Covalent glutathione conjugation to cyanobacterial hepatotoxin microystin-LR by F344 rat cytosolic and microsomal glutathione S-transferases. Environ Toxicol Phar, 2001,9:135-139.
    172. Tang, Y. Evaluation of balance between fishes and available fish foods in multispecies fish culture ponds in Taiwan. Trans Am Fish Soc, 1981, 99:708-717.
    173. Tencalla F, Dietrich D. Biochemical characterization of microcystin toxicity in rainbow trout (Oncorhynchus Mykiss). Toxicon, 1997,35:583-595.
    174. Tsuji, K., Watanuki, T., Kondo, F., Watanabe, M.F., Suzuki, S., Nakazawa, H., Suzuki, M., Uchida, H., Harada, K.I. Stability of microcystins from cyanobacteria-II: effect of UV light on decomposition and isomerization. Toxicon, 1995, 33:1619-1631.
    175. Ueno, Y., Nagata, S., Tsutsumi, T., Hasegawa, A., Watanabe, M.F., Park, H.D., Chen, G.C., Chen, G., Yu, S.-Z. Detection of microcystins, a blue-green algal hepatotoxin, in drinking water sampled in Haimen and Fusui, endemic areas of primary liver cancer in China, by highly sensitive immunoassay. Carcinogenesis, 1996, 17:1317-1321.
    176. Vajcova, V., Navratil, S., Palikova, M. The effect of intraperitoneally applied pure microcystin-LR on haematological and morphological indices of silver carp (Hypophthalmichthys molitrix Val.). Acta Veterinaria Brno, 1998, 67(4):281-287.
    177. Watanabe, M.F., Oishi, S., Harada, K.I., Matsuurak, K., Kawai, H., Suzuki, M. Toxins contained in Microcystis specis of cyanobacteria (blue-green alga). Toxicon, 1988, 26:1017-1025.
    178. WHO. Guidelines for Drinking-water Quality, Second ed., Addendum to vol. 2, Health Criteria and Other Supporting Information. Geneva: World Health Organization, 1998, pp 95-110.
    179. Wickstrom, M., Haschek, W., Henningsen, G., Miller, L.A., Wyman, J., Beasley, V.R. Sequential ultrastructural and biochemical changes induced by Microcystin-LR in isolated perfused rat livers. Natural toxins, 1996, 4:195-205.
    180. Wickstrom, M.L., Khan, S.A., Haschek, W.M., Wyman, J.F., Eriksson, J.E., Schaeffer, D.J., Beasley, V.R. Alterations in microtubules, intermediate filaments, and microfilaments induced by microcystin-LR in cultured cells. Toxicol Pathol, 1995, 23:325-337.
    181. Wiegand, C., Pflugmacher, S., Oberemm, A., Meems, N., Beattie, K.A.,Steinberg, C.E.W., Codd, G.A. Uptake and effects of microcystin-LR on detoxication enzymes of early life stages of the zebra fish (Diano rerio). Environ Toxicol, 1999, 14(1):89-95.
    182. Willams, D.E., Dawe, S.C., Kent, M.L., Andersen, R.J., Craig, M., Holmes, C.F.B. Bioaccumulation and clearance of microcytins from salt water mussels, Mytilus edulis, and in vivo evidence for covalently bound microcystins in mussel tissues. Toxicon, 1997, 35:1617-1625.
    183. Williams, D.E., kent, M.L., Andersen, R.J., Klix, H., Holmes, C.F.B. Tissue distribution and clearance of tritium-labeled dihydromicrocystin-LR epimers administered to Atlantic salmon via intraperitoneal injection. Toxin, 1995, 33(2):125-131.
    184. Wyllie, A.H., Kerr, J.F.R., Currie, A.R. Cell death: the significance of apoptosis. Int. Rev. Cytol., 1980, 68:251-305.
    185. Xie, L.Q., Xie, P., Guo, L.G., Li, L., Yuichi, M., Park, H.D. Organ distribution and bioaccumulation of microcystins in freshwater fish at different trophic levels from the eutrophic lake Chaohu, China. Environ Toxicol, 2005, 20:293-300.
    186. Xie, L.Q., Xie, P., Ozawa, K., Honma, T., Yokoyama, A., Park, H.D. Dynamics of microcystins-LR and –RR in the phytoplanktivorous silver carp in a sub-chronic toxicity experiment. Environ Pollu, 2004, 127:431-439.
    187. Xie, P., Liu, J.K. Practical success of biomanipulation using filter-feeding fish to control cyanobacteria blooms: synthesis of decades of research and application in a subtropical hypereutrophic lake. Sci World J, 2001, 1:337-356.
    188. Yoshida, T., Makita, Y., Nagata, S., Tsutsumi, T., Yoshida, F., Sekijima, M., Tamura, S., Ueno, Y. Acute oral toxicity of microcytstin-LR, a cyanobacterial hepatotoxin, in mice. Nat Toxin, 1997, 5:91-95.
    189. Zambrano, F., Canelo, E. Effects of microcystin-LR on the partialreactions of the Na super (+)-K super (+) pump of the gill of carp (Cyprinus carpil Linneo). Toxicon, 1996, 34(4):451-458.
    190. Z?gura, B., Sedmark, B., Filipi?, M. Microcystin-LR induces oxidative DNA damage in human hepatoma cell line HepG2. Toxicon, 2003, 41:41-48.
    191. Zimba, P.V., Khoo, L., Gaunt, P.S., Bittain, S., Carmichael, W.W. Confirmation of catfish, Ictalurus punctatus (Rafinesque) mortality from Microcystis toxins. J Fish Dis, 2001, 24:41-47.

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