Oxidative stress generation by microcystins in aquatic animals: Why and how

Environment International

Volumn 36, Issue 2, 2010, Pages 226-235

  Amado, L L ^a,b   Monserrat, J M ^a,b  

^a Curso de Pos graduacao em Ciencias Fisiologicas Fisiologia Animal Comparada   (Brazil)

^b FEDERAL UNIVERSITY OF RIO GRANDE   (Brazil)

Author keywords

Aquatic organisms; Hyperphosphorylation; Microcystins toxicity; Oxidative stress; Phosphorylation of antioxidant enzymes

Indexed keywords

ANIMALS; ANTIOXIDANTS; ENZYMES; METABOLITES; MICROWAVE INTEGRATED CIRCUITS; OXIDATIVE STRESS; TOXICITY;

ANTIOXIDANT ENZYME; CELLULAR ENVIRONMENT; HYPERPHOSPHORYLATED; HYPERPHOSPHORYLATION; MECHANISTIC ASPECTS; MICROCYSTINS TOXICITY; REACTIVE OXYGEN SPECIES; STRESS GENERATION;

AQUATIC ORGANISMS;

GLUTATHIONE TRANSFERASE; MICROCYSTIN; REACTIVE OXYGEN METABOLITE;

ANTIOXIDANT; AQUATIC ORGANISM; CYANOBACTERIUM; ENZYME ACTIVITY; INHIBITION; POLLUTION EFFECT; POLLUTION EXPOSURE; TOXICITY; TOXIN;

AQUATIC SPECIES; CHEMICAL ANALYSIS; CHEMOPROPHYLAXIS; CONCENTRATION (PARAMETERS); CYANOBACTERIUM; CYTOTOXICITY; ENVIRONMENTAL EXPOSURE; ENZYME ACTIVITY; NONHUMAN; NUCLEOTIDE SEQUENCE; OXIDATIVE STRESS; PRIORITY JOURNAL; REVIEW; SYNTHESIS;

ANIMALIA; CYANOBACTERIA;

EID: 73249127370     PISSN: 01604120     EISSN: 18736750     Source Type: Journal    
DOI: 10.1016/j.envint.2009.10.010     Document Type: Review

References (122)

1. Amado L.L., Garcia M.L., Ramos P.B., Freitas R.F., Zafalon B., Ferreira J.L.R., et al. A method to measure total antioxidant capacity against peroxyl radicals in aquatic organisms: application to evaluate microcystins toxicity. Sci Total Environ 407 (2009) 2115-2123
2. Amorim Á., and Vasconcelos V. Dynamics of microcystins in the mussel Mytilus galloprovincialis. Toxicon 37 (1999) 1041-1052
3. Aon M.A., Cortassa S., Maack C., and O'Rourke B. Sequential opening of mitochondrial ion channels as a function of glutathione redox thiol status. J Biol Chem 282 (2007) 21889-21900
4. Atencio L., Moreno I., Jos A., Pichardo S., Moyano R., Blanco A., et al. Dose-dependent antioxidant responses and pathological changes in tenca (Tinca tinca) after acute oral exposure to Microcystis under laboratory conditions. Toxicon 52 (2008) 1-12
5. Baganz D., Staaks G., Pflugmacher S., and Steinberg C.E.W. Comparative study of microcystin-LR-induced behavioral changes of two fish species, Danio rerio and Leucaspius delineatus. Environ Toxicol 19 (2004) 564-570
6. Best J.H., Eddy F.B., and Codd G.A. Effects of purified microcystin-LR and cell extracts of Microcystis strains PCC 7813 and CYA 43 on cardiac function in brown trout (Salmo trutta) alevins. Fish Physiol Biochem 24 (2001) 171-178
7. Best J.H., Pflugmacher S., Wiegand C., Eddy F.B., Metcalf J.S., and Codd G.A. Effects of enteric bacterial and cyanobacterial lipopolysaccharides, and of microcystin-LR, on glutathione S-transferase activities in zebra fish (Danio rerio). Aquat Toxicol 60 (2002) 223-231
8. Bláha L., Kopp R., Imková K., and Mares J. Oxidative stress biomarkers are modulated in silver carp (Hypophthalmichthys molitrix Val.) exposed to microcystin-producing cyanobacterial water bloom. Acta vet Brno 73 (2004) 477-482
9. Blom N., Gammeltoft S., and Brunak S. Sequence- and structure-based prediction of eukaryotic protein phosphorylation sites. J Mol Biol 294 (1999) 1351-1362
10. Bury N.R., Eddy F.B., and Codd G.A. The effects of the cyanobacterium Microcystis aeruginosa, the cyanobacterial hepatotoxin microcystin-LR, and ammonia on growth rate and ionic regulation of brown trout. J Fish Biol 46 (1995) 1042-1054
11. + ATPase in tilapia gills. J Exp Biol 199 (1996) 1319-1326
12. Burýsková B., Hilscherová K., Babica P., Vrsková D., Marsálek B., and Bláha L. Toxicity of complex cyanobacterial samples and their fractions in Xenopus laevis embryos and the role of microcystins. Aquat Toxicol 80 (2006) 346-354
13. Cao C., Leng Y., Huang W., Liu X., and Kufe D. Glutathione peroxidase 1 is regulated by the c-abl and arg tyrosine kinases. J Biol Chem 278 (2003) 39609-39614
14. Cao C., Leng Y., and Kufe D. Catalase activity is regulated by c-abl and arg in the oxidative stress response. J Biol Chem 278 (2003) 29667-29675
15. Carmichael W. A world overview - one-hundred twenty-seven years of research on toxic cyanobacteria - where do we go from here?. In: Kenneth Hudnell H. (Ed). Proceedings of the interagency, international symposium on cyanobacterial harmful algal blooms. Advances in Experimental Medicine and Biology (2007) 95-115
16. Cazenave J., Wunderlin D.A., Bistoni M.d.l.Á., Amé M.V., Krause E., Pflugmacher S., et al. Uptake, tissue distribution and accumulation of microcystin-RR in Corydoras paleatus, Jenynsia multidentata and Odontesthes bonariensis: a field and laboratory study. Aquat Toxicol 75 (2005) 178-190
17. Cazenave J., Bistoni M.d.l.A., Zwirnmann E., Wunderlin D.A., and Wiegand C. Attenuating effects of natural organic matter on microcystin toxicity in zebra fish (Danio rerio) embryos - benefits and costs of microcystin detoxication. Environ Toxicol 21 (2006) 22-32
18. Cazenave J., Bistoni M.d.l.A., Pesce S.F., and Wunderlin D.A. Differential detoxification and antioxidant response in diverse organs of Corydoras paleatus experimentally exposed to microcystin-RR. Aquat Toxicol 76 (2006) 1-12
19. Cazenave J., Nores M.L., Miceli M., Díaz M.P., Wunderlin D.A., and Bistoni M.A. Changes in the swimming activity and the glutathione S-transferase activity of Jenynsia multidentata fed with microcystin-RR. Water Res 42 (2008) 1299-1307
20. Chang T.-S., Jeong W., Choi S.Y., Yu S., Kang S.W., and Rhee S.G. Regulation of peroxiredoxin 1 activity by cdc2-mediated phosphorylation. J Biol Chem 277 (2002) 25370-25376
21. Chen J., and Xie P. Tissue distributions and seasonal dynamics of the hepatotoxic microcystins-LR and -RR in two freshwater shrimps, Palaemon modestus and Macrobrachium nipponensis, from a large shallow, eutrophic lake of the subtropical China. Toxicon 45 (2005) 615-625
22. Chen J., Xie P., Zhang D., Ke Z., and Yang H. In situ studies on the bioaccumulation of microcystins in the phytoplanktivorous silver carp (Hypophthalmichthys molitrix) stocked in Lake Taihu with dense toxic Microcystis blooms. Aquaculture 261 (2006) 1026-1038
23. Chen Y.-M., Lee T.-H., Lee S.-J., Huang H.-B., Huang R., and Chou H.-N. Comparison of protein phosphatase inhibition activities and mouse toxicities of microcystins. Toxicon 47 (2006) 742-746
24. Chen J., Zhang D., Xie P., Wang Q., and Ma Z. Simultaneous determination of microcystin contaminations in various vertebrates (fish, turtle, duck and water bird) from a large eutrophic Chinese lake, Lake Taihu, with toxic Microcystis blooms. Sci Total Environ 407 (2009) 3317-3322
25. Chernyak B.V. Redox, regulation of the mitochondrial permeability transition pore. Biosci Rep 17 (1997) 293-302
26. Chorus I., and Bartram J. Toxic cyanobacteria in water: a guide to public health significance, monitoring and management (1999), WHO, E and FN Spon/Chapman and Hall, London 416 pp
27. Contardo-Jara V., Pflugmacher S., and Wiegand C. Multi-xenobiotic-resistance a possible explanation for the insensitivity of bivalves towards cyanobacterial toxins. Toxicon 52 (2008) 936-943
28. Csar X.F., Wilson N.J., Strike P., Sparrow L., McMahon K.A., Ward A.C., et al. Copper/zinc superoxide dismutase is phosphorylated and modulated specifically by granulocyte-colony stimulating factor in myeloid cells. Proteomics 1 (2001) 435-443
29. Dawson R.M. The toxicology of microcystins. Toxicon 36 (1998) 953-962
30. de Figueiredo D.R., Azeiteiro U.M., Esteves S.M., Gonçalves F.J.M., and Pereira M.J. Microcystin-producing blooms - a serious global public health issue. Ecotoxicol Environ Saf 59 (2004) 151-163
31. DeMott W., and Dhawale S. Inhibition of in vitro protein phosphatase activity in three zooplankton species by microcystin-LR, a toxin from cyanobacteria. Arch Hydrobiol 34 (1995) 417-424
32. Dewes L.J., Sandrini J.Z., Monserrat J.M., and Yunes J.S. Biochemical and physiological responses after exposure to microcystins in the crab Chasmagnathus granulates (Decapoda, Brachyura). Ecotoxicol Environ Saf 65 (2006) 201-208
33. Dickinson D.A., and Forman H.J. Cellular glutathione and thiols metabolism. Biochem Pharmacol 64 (2002) 1019-1026
34. Ding W.-X., and Ong C.N. Role of oxidative stress and mitochondrial changes in cyanobacteria-induced apoptosis and hepatotoxicity. FEMS Microbiol Lett 220 (2003) 1-7
35. Ding W.-X., Shen H.-M., and Ong C.-N. Critical role of reactive oxygen species and mitochondrial permeability transition in microcystin-induced rapid apoptosis in rat hepatocytes. Hepatology 32 (2000) 547-555
36. Ding W.-X., Shen H.M., and Ong C.-N. Microcystic cyanobacteria extract induces cytoskeletal disruption and intracellular glutathione alteration in hepatocytes. Environ Health Perspect 108 (2000) 605-609
37. Ding W.-X., Shen H.-M., and Ong C.-N. Critical role of reactive oxygen species formation in microcystin-induced cytoskeleton disruption in primary cultured hepatocytes. J Toxicol Environ Health 64 (2001) 507-519
38. Ding W.-X., Shen H.-M., and Ong C.-N. Calpain activation after mitochondrial permeability transition in microcystin-induced cell death in rat hepatocytes. Biochem Biophys Res Commun 291 (2002) 321-331
39. Eriksson J.E., Meriluoto J.A.O., and Lindholm T. Accumulation of a peptide toxin from the cyanobacterium Oscillatoria agardhii in the freshwater mussel Anadonta cygnea. Hydrobiologia 183 (1989) 211-216
40. Fischer W.J., and Dietrich D.R. Toxicity of the cyanobacterial cyclic heptapeptide toxins microcystin-LR and -RR in early life-stages of the African clawed frog (Xenopus laevis). Aquat Toxicol 49 (2000) 189-198
41. Fischer W.J., and Dietrich D.R. Pathological and biochemical characterization of microcystin-induced hepatopancreas and kidney damage in carp (Cyprinus carpio). Toxicol Appl Pharmacol 164 (2000) 73-81
42. Fischer W.J., Hitzfeld B.C., Tencalla F., Eriksson J.E., Mikhailov A., and Dietrich D.R. Microcystin-LR toxicodynamics, induced pathology, and immunohistochemical localization in livers of blue-green algae exposed rainbow trout (Oncorhynchus mykiss). Toxicol Sci 54 (2000) 365-373
43. Fischer W.J., Altheimer S., Cattori V., Meier P.J., Dietrich D.R., and Hagenbuch B. Organic anion transporting polypeptides expressed in liver and brain mediate uptake of microcystin. Toxicol Appl Pharmacol 203 (2005) 257-263
44. Gaete V., Canelo E., Lagos N., and Zambrano F. Inhibitory effects of Microcystis aeruginosa toxin on ion pumps of the gill of freshwater fish. Toxicon 32 (1994) 121-127
45. Gehringer M.M., Shephard E.G., Downing T.G., Wiegand C., and Neilan B.A. An investigation into the detoxification of microcystin-LR by the glutathione pathway in Balb/c mice. Int J Biochem Cell Biol 36 (2004) 931-941
46. Guo G.L., and Klaassen C.D. Protein kinase C suppresses rat organic anion transporting polypeptide 1- and 2-mediated uptake. J Pharmacol Exp Ther 299 (2001) 551-557
47. Hagenbuch B., and Meier P.J. The superfamily of organic anion transporting polypeptides. Biochim Biophys Acta 1609 (2003) 1-18
48. In: Halliwell B., and Gutteridge J.M.C. (Eds). Free radicals in biology and medicine. Fourth ed (2007), Oxford University Press, New York
49. Heinze R. Toxicity of the cyanobacterial toxin microcystin-LR to rats after 28 days intake with the drinking water. Environ Toxicol 14 (1999) 57-60
50. Hermes-Lima M. Oxygen in biology and biochemistry: role of free radicals. In: Storey K.B. (Ed). Functional metabolism: regulation and adaptation (2004), John Wiley and Sons, New York 319-368
51. Hernández J.M., López-Rodas V., and Costas E. Microcystins from tap water could be a risk factor for liver and colorectal cancer: a risk intensified by global change. Med Hypotheses 72 (2009) 539-540
52. Hofmann B., Hecht H.J., and Flohé L. Peroxiredoxins. Biol Chem. 383 (2002) 347-364
53. Hu Z., Chen H., Pang C., and Lin Q. The expression of p53 and p16 in the course of microcystin-LR inducing of liver tumor. Chin Ger J Clin Oncol 7 (2008) P690-P693
54. Huang H.-C., Nguyen T., and Pickett C.B. Phosphorylation of Nrf2 at Ser-40 by protein kinase C regulates antioxidant response element-mediated transcription. J Biol Chem 277 (2002) 42769-42774
55. Ibelings B.W., and Chorus I. Accumulation of cyanobacterial toxins in freshwater "seafood" and its consequences for public health: a review. Environ Pollut 150 (2007) 177-192
56. Jones D.P. Redefining oxidative stress. Antioxid Redox Signal 8 (2006) 1865-1879
57. Jos Á., Pichardo S., Prieto A.I., Repetto G., Vázquez C.M., Morenoa I., et al. Toxic cyanobacterial cells containing microcystins induce oxidative stress in exposed tilapia fish (Oreochromis sp.) under laboratory conditions. Aquat Toxicol 72 (2005) 261-271
58. Juhel G., Davenport J., O'Halloran J., Culloty S., Ramsay R., James K., et al. Pseudodiarrhoea in zebra mussels Dreissena polymorpha (Pallas) exposed to microcystins. J Exp Biol 209 (2006) 810-816
59. Kamjunke N., Mendonca R., Hardewig I., and Mehner T. Assimilation of different cyanobacteria as food and the consequences for internal energy stores of juvenile roach. J Fish Biol 60 (2002) 731-738
60. Kobayashi M., Li L., Iwamoto N., Nakajima-Takagi Y., Kaneko H., Nakayama Y., et al. The antioxidant defense system Keap1-Nrf2 comprises a multiple sensing mechanism for responding to a wide range of chemical compounds. Mol Cell Biol 29 (2009) 493-502
61. Kwak M.-K., Wakabayashi N., and Kensler T.W. Chemoprevention through the Keap1-Nrf2 signaling pathway by phase 2 enzyme inducers. Mutat Res 555 (2004) 133-148
62. Leão J.C., Geracitano L.A., Monserrat J.M., Amado L.L., and Yunes J.S. Microcystin-induced oxidative stress in Laeonereis acuta (Polychaeta, Nereididae). Mar Environ Res 66 (2008) 92-94
63. Lee J., and Surh Y. Nrf2 as a novel molecular target for chemoprevention. Cancer Lett 224 (2005) 171-184
64. Li X., Liu Y., Song L., and Liu J. Responses of antioxidant systems in the hepatocytes of common carp (Cyprinus carpio L.) to the toxicity of microcystin-LR. Toxicon 42 (2003) 85-89
65. Li X.-Y., Chung I.-K., Kim J.-I., and Lee J.-A. Subchronic oral toxicity of microcystin in common carp (Cyprinus carpio L.) exposed to Microcystis under laboratory conditions. Toxicon 44 (2004) 821-827
66. Li X.-Y., Chung I.-K., Kim J.-I., and Lee J.-A. Oral exposure to Microcystis increases activity-augmented antioxidant enzymes in the liver of loach (Misgurnus mizolepis) and has no effect on lipid peroxidation. Comp Biochem Physiol C 141 (2005) 292-296
67. Li D., Xie P., and Zhang X. Changes in plasma thyroid hormones and cortisol levels in crucian carp (Carassius auratus) exposed to the extracted microcystins. Chemosphere 74 (2008) 13-18
68. Li G., Xie P., Fu J., Hao L., Xiong Q., and Li H. Microcystin-induced variations in transcription of GSTs in an omnivorous freshwater fish, goldfish. Aquat Toxicol 88 (2008) 75-80
69. Li H., Xie P., Li G., Hao L., and Xiong Q. In vivo study on the effects of microcystin extracts on the expression profiles of proto-oncogenes (c-fos, c-jun and c-myc) in liver, kidney and testis of male Wistar rats injected i.v. with toxins. Toxicon 53 (2009) 169-175
70. Lo H.-W.L., Antoun G.R., and Ali-Osman F. The human glutathione S-transferase P1 protein is phosphorylated and its metabolic function enhanced by the Ser/Thr protein kinases, cAMP-dependent protein kinase and protein kinase C, in glioblastoma cells. Cancer Res 64 (2004) 9131-9138
71. Maher P. The effects of stress and aging on glutathione metabolism. Ageing Res Rev 4 (2005) 288-314
72. Malbrouck C., and Kestemont P. Effects of microcystins on fish. Environ Toxicol Chem 25 (2006) 72-86
73. Martins J.C., and Vasconcelos V.M. Microcystin dynamics in aquatic organisms. J Toxicol Environ Health 12 (2009) 65-82
74. Meier-Abt F., Hammann-Hänni A., Stieger B., Ballatori N., and Boyer J.L. The organic anion transport polypeptide 1d1 (Oatp1d1) mediates hepatocellular uptake of phalloidin and microcystin into skate liver. Toxicol Appl Pharmacol 218 (2007) 274-279
75. Meister A. Mitochondrial changes associated with glutathione deficiency. Biochim Biophys Acta 1271 (1995) 35-42
76. Metcalf J.S., Beattie K.A., Pflugmacher S., and Codd G.A. Immuno-crossreactivity and toxicity assessment of conjugation products of the cyanobacterial toxin, microcystin-LR. FEMS Microbiol Lett 189 (2000) 155-158
77. Mikhailov A., Härmälä-Braskén A.-S., Hellman J., Meriluoto J., and Eriksson J.E. Identification of ATP-synthase as a novel intracellular target for microcystin-LR. Chem Biol Interact 142 (2003) 223-237
78. Milutinovi A., Zivin M., Zorc-Pleskovic R., Sedmak B., and Suputa D. Nephrotoxic effects of chronic administration of microcystins -LR and -YR. Toxicon 42 (2003) 281-288
79. Miyazaki H., Sekine T., and Endou H. The multispecific organic anion transporter family: properties and pharmacological significance. Trends Pharmacol Sci 25 (2004) 654-662
80. Mohamed Z.A. Accumulation of cyanobacterial hepatotoxins by Daphnia in some Egyptian irrigation canals. Ecotoxicol Environ Saf 50 (2001) 4-8
81. Monserrat J.M., Lima J.V., Ferreira J.L.R., Acosta D., Garcia M.L., Ramos P.B., et al. Modulation of antioxidant and detoxification responses mediated by lipoic acid in the fish Corydoras paleatus (Callychthyidae). Comp Biochem Physiol C 148 (2008) 287-292
82. Oberemm A., Fastner J., and Steinberg C.E.W. Effects of microcystin-LR and cyanobacterial crude extracts on embryo-larval development of zebrafish (Danio rerio). Water Res 31 (1997) 2918-2921
83. Oberemm A., Becker J., Codd G.A., and Steinberg C. Effects of cyanobacterial toxins and aqueous crude extracts of cyanobacteria on the development of fish and amphibians. Environ Toxicol 14 (1999) 77-88
84. Okamura T., Singh S., Buolamwini J., Haystead T.A., Friedman H.S., Bigner D.D., et al. Tyrosine phosphorylation of the human glutathione S-transferase p1 by epidermal growth factor receptor. J Biol Chem M808153200 (2009)
85. Packer L., Witt E.H., and Tritschler H.J. Alpha-lipoic acid as a biological antioxidant. Free Radic Biol Med 19 (1995) 227-250
86. Pflugmacher S., Wiegand C., Oberemm A., Beattie K.A., Krause E., Codd G.A., et al. Identification of an enzimatically formed glutathione conjugate of the cyanobacterial hepatoxin microcystin-LR: the first step of detoxication. Biochim Biophys Acta 1425 (1998) 527-533
87. Pietsch C., Wiegand C., Amé M.V., Nicklisch A., Wunderlin D., and Pflugmacher S. The effects of a cyanobacterial crude extract on different aquatic organisms: evidence for cyanobacterial toxin modulating factors. Environ Toxicol 16 (2001) 535-542
88. Pinho G.L.L., Moura da Rosa C., Yunes J.S., Luquet C.M., Bianchini A., and Monserrat J.M. Toxic effects of microcystins in the hepatopancreas of the estuarine crab Chasmagnathus granulatus (Decapoda, Grapsidae). Comp Biochem Physiol C 135 (2003) 459-468
89. Pinho G.L.L., Moura da Rosa C., Maciel F.E., Bianchini A., Yunes J.S., Proença L.A.O., et al. Antioxidant responses and oxidative stress after microcystin exposure in the hepatopancreas of an estuarine crab species. Ecotoxicol Environ Saf 61 (2005) 353-360
90. Pires L.M.D., Kusserow R., and Van Donk E. Influence of toxic and non-toxic phytoplankton on feeding and survival of Dreissena polymorpha (Pallas) larvae. Hydrobiologia 491 (2003) 193-200
91. Prieto A.I., Jos A., Pichardo S., Moreno I., and Cameán A.M. Differential oxidative stress responses to microcystins LR and RR in intraperitoneally exposed tilapia fish (Oreochromis sp.). Aquat Toxicol 77 (2006) 314-321
92. Prieto A.I., Pichardo S., Jos Á., Moreno I., and Cameán A.M. Time-dependent oxidative stress responses after acute exposure to toxic cyanobacterial cells containing microcystins in tilapiafish (Oreochromis niloticus) under laboratory conditions. Aquat Toxicol 84 (2007) 337-345
93. Qiu T., Xie P., Guo L., and Zhang D. Plasma biochemical responses of the planktivorous filter-feeding silver carp (Hypophthalmichthys molitrix) and bighead carp (Aristichthys nobilis) to prolonged toxic cyanobacterial blooms in natural waters. Environ Toxicol Pharmacol 27 (2009) 350-356
94. 2: regulation of peroxiredoxin, catalase, and glutathione peroxidase via post-translational modification. Antioxid Redox Signal 7 (2005) 619-626
95. Rosa C.E., de Souza M.S., Yunes J.S., Proença L.A.O., Nery L.E.M., and Monserrat J.M. Cyanobacterial blooms in estuarine ecosystems: characteristics and effects on Laeonereis acuta (Polychaeta, Nereididae). Mar Pollut Bull 50 (2005) 956-964
96. Runnegar M.T.C., Andrews J., Gerdes R.G., and Falconer I.R. Injury to hepatocytes induced by a peptide toxin from the cyanobacterium Microcystis aeruginosa. Toxicon 25 (1987) 1235-1239
97. Runnegar M., Berndt N., and Kaplowitz N. Microcystin uptake and inhibition of protein phosphatases: effects of chemoprotectants and self-inhibition in relation to known hepatic transporters. Toxicol Appl Pharmacol 134 (1995) 264-272
98. Sauvant C., Hesse D., Holzinger H., Evans K.K., Dantzler W.H., and Gekle M. Action of EGF and PGE2 on basolateral organic anion uptake in rabbit proximal renal tubules and hOAT1 expressed in human kidney epithelial cells. Am J Physiol Renal Physiol 286 (2004) F774-F783
99. Seki H., Takahashi M., Hara Y., and Ichimura S. Dynamics of dissolved oxygen during algal bloom in lake Kasumigaura, Japan. Water Res 14 (1980) 179-183
100. Shila S., Kokilavani V., Subathra M., and Panneerselvam C. Brain regional responses in antioxidant system to [alpha]-lipoic acid in arsenic intoxicated rat. Toxicology 210 (2005) 25-36
101. Soares R.M., Magalhães V.F., and Azevedo S.M.F.O. Accumulation and depuration of microcystins (cyanobacteria hepatotoxins) in Tilapia rendalli (Cichlidae) under laboratory conditions. Aquat Toxicol 70 (2004) 1-10
102. Suh J.H., Shenvi S.V., Dixon B.M., Liu H., Jaiswal A.K., Liu R.-M., et al. Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Proc Natl Acad Sci 101 (2004) 3381-3386
103. Sun W.-M., Huang Z.-Z., and Lu S.C. Regulation of γ-glutamylcysteine synthetase by protein phosphorylation. Biochem J 320 (1996) 321-328
104. Svrcek C., and Smith D.W. Cyanobacteria toxins and the current state of knowledge on water treatment options: a review. J Environ Eng Sci 3 (2004) 155-185
105. Toroser D., Yarian C.S., Orr W.C., and Sohal R.S. Mechanisms of γ-glutamylcysteine ligase regulation. Biochim Biophys Acta 1760 (2006) 233-244
106. Uwai Y., Okuda M., Takami K., Hashimoto Y., and Inui K.-I. Functional characterization of the rat multispecific organic anion transporter OAT1 mediating basolateral uptake of anionic drugs in the kidney. FEBS Lett 438 (1998) 321-324
107. Vinagre T.M., Alciati J.C., Regoli F., Bocchetti R., Yunes J.S., Bianchini A., et al. Effect of hepatotoxins (microcystin) on ion-regulation and antioxidant system in gills of Chasmagnathus granulatus (Decapoda, Grapsidae). Comp Biochem Physiol C 135 (2003) 67-75
108. Votto A.P.S., Renon V.P., Yunes J.S., Rumjanek V.M., Marques Capella M.A., Moura Neto V., et al. Sensitivity to microcystins: a comparative study in human cell lines with and without multidrug resistance phenotype. Cell Biol Int 31 (2007) 1359-1366
109. White C.C., Viernes H., Krejsa C.M., Botta D., and Kavanagh T.J. Fluorescence-based microtiter plate assay for glutamate-cysteine ligase activity. Anal Biochem 318 (2003) 175-180
110. Wiegand C., and Pflugmacher S. Ecotoxicological effects of selected cyanobacterial secondary metabolites a short review. Toxicol Appl Pharmacol 203 (2005) 201-218
111. Wiegand C., Pflugmacher S., Oberemm A., Meems N., Beattie K.A., Steinberg C.E.W., et al. Uptake and effects of microcystin-LR on detoxication enzymes of early life stages of the zebra fish (Danio rerio). Environ Toxicol 14 (1999) 89-95
112. Winston G.W., Regoli F., Dugas Jr. A.J., Fong J.H., and Blanchard K.A. A rapid gas chromatographic assay for determining oxyradical scavenging capacity of antioxidants and biological fluids. Free Radic Biol Med 24 (1998) 480-493
113. Wolff N.A., Thies K., Kuhnke N., Reid G., Friedrich B., Lang F., et al. Protein kinase C activation downregulates human organic anion transporter 1-mediated transport through carrier internalization. J Am Soc Nephrol 14 (2003) 1959-1968
114. Xie L., Xie P., Ozawa K., Honma T., Yokoyama A., and Park H.-D. Dynamics of microcystins-LR and -RR in the phytoplanktivorous silver carp in a sub-chronic toxicity experiment. Environ Pollut 127 (2004) 431-439
115. You G., Kuze K., Kohanski R.A., Amsler K., and Henderson S. Regulation of mOAT-mediated organic anion transport by okadaic acid and protein kinase C in LLC-PK1 cells. J Biol Chem 275 (2000) 10278-10284
116. Zegura B., Sedmak B., and Filipic M. Microcystin-LR induces oxidative DNA damage in human hepatoma cell line HepG2. Toxicon 41 (2003) 41-48
117. Zegura B., Zajc I., Lah T.T., and Filipic M. Patterns of microcystin-LR induced alteration of the expression of genes involved in response to DNA damage and apoptosis. Toxicon 51 (2008) 615-623
118. Zhang J., Zhang H., and Chen Y. Sensitive apoptosis induced by microcystins in the crucian carp (Carassius auratus) lymphocytes in vitro. Toxicol In Vitro 20 (2006) 560-566
119. 2+, mitochondria membrane potential, reactive oxygen species, and intracellular ATP on the mechanism of microcystin-LR induced apoptosis in Carassius auratus lymphocytes in vitro. Environ Toxicol 22 (2007) 559-564
120. Zhang H., Zhang J., Chen Y., and Zhu Y. Microcystin-RR induces apoptosis in fish lymphocytes by generating reactive oxygen species and causing mitochondrial damage. Fish Physiol Biochem 34 (2008) 307-312
121. Zhang D., Xie P., Liu Y., and Qiu T. Transfer, distribution and bioaccumulation of microcystins in the aquatic food web in Lake Taihu, China, with potential risks to human health. Sci Total Environ 407 (2009) 2191-2199
122. Zhao M., Xie S., Zhu X., Yang Y., Gan N., and Song L. Effect of dietary cyanobacteria on growth and accumulation of microcystins in Nile tilapia (Oreochromis niloticus). Aquaculture 261 (2006) 960-966