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Abstract

Microcystins (MCs) released during cyanobacterial blooms induce immense toxic manifestations in animals and humans. The International Agency for Research on Cancer (IARC) categorized MC as a possible carcinogen. Research indicates that aside from the liver, MCs can negatively impact the intestine. Interestingly, less attention exists with respect to MCs effects on the intestine in spite of the organ being the focal site of the toxins’ uptake. Compiling data from in vivo and in vitro studies, the current review summarized available literature on the impact of MCs on intestinal health. In addition, the toxins’ uptake, accumulation, and various methods used to determine intestinal toxicity were elucidated.

Keywords

Microcystins Intestine Transport Toxicity and carcinogenicity Detection

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Yaw Massey, I., Osei, E., Ampon-Wireko, S., Sarponmaa Asante, L., Ayawine, A., Kwang, E., Ojo, L., & Yaw Opoku, S. (2023). A Review on the Uptake, Accumulation, Impact and Determinants of Microcystins on Intestinal Health. International Journal of Multidisciplinary Studies and Innovative Research, 11(3), 1448–1473. https://doi.org/10.53075/Ijmsirq/87645654465
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References

  1. Alosman, M., Massey, I. Y, & Yang Fei. (2020). The lethal effects and determinants of microcystin-LR on
  2. heart: a mini review. Toxin Reviews. doi: 10.1080/15569543.2019.171141
  3. Amrani, A., Nasri, H., Azzouz, A., Kadi, Y., & Bouaicha, N. (2014). Variation in Cyanobacterial Hepatotoxin
  4. (Microcystin) Content of Water Samples and Two Species of Fishes Collected from a Shallow Lake in Algeria. Archives of Environmental Contamination and Toxicology, 66, 379-389. doi: 10.1007/s00244-013-9993-2
  5. Bi, X. D., Dai, W., Wang, X. Y., Dong, S. J., Zhang, S. L., Zhang, D. J., & Wu, M. (2019). Microcystins
  6. distribution, bioaccumulation, and Microcystis genotype succession in a fish culture pond. Science of the Total Environment, 688, 380-388. doi: 10.1016/j.scitotenv.2019.06.156
  7. Botha, N., Gehringer, M. M., Downing, T. G., van de Venter, M., & Shephard, E. G. (2004a). The role of
  8. microcystin-LR in the induction of apoptosis and oxidative stress in CaCo2 cells. Toxicon, 43, 85-92. doi: 10.1016/j.toxicon.2003.10.025
  9. Botha, N., van de Venter, M., Downing, T. G., Shephard, E. G., & Gehringer, M. M. (2004b). The effect of
  10. intraperitoneally administered microcystin-LR on the gastrointestinal tract of Balb/c mice. Toxicon, 43, 251-254. doi: 10.1016/j.toxicon.2003.11.026
  11. Bouaicha, N., Miles, C. O., Beach, D. G., Labidi, Z., Djabri, A., Benayache, N. Y., & Nguyen-Quang, T.
  12. (2019). Structural Diversity, Characterization and Toxicology of Microcystins. Toxins, 11, 714. doi: 10.3390/toxins11120714
  13. Cao, L., Huang, F., Massey, I. Y., Wen, C., Zheng, S., Xu, S., & Yang, F. (2019). Effects of Microcystin-LR
  14. on the Microstructure and Inflammation-Related Factors of Jejunum in Mice. Toxins, 11, 482. doi: 10.3390/toxins11090482
  15. Chen, C., Liu, W. J., Wang, L., Li, J., Chen, Y. Y., Jin, J. N., Kawan, A., & Zhang, X. Z. (2016). Pathological
  16. damage and immunomodulatory effects of zebrafish exposed to microcystin-LR. Toxicon, 118, 13-20. doi: 10.1016/j.toxicon.2016.04.030
  17. Chia, M. A., Auta, Z. Z., Esson, A. E., Yisa, A. G., & Abolude, D. S. (2019). Assessment of microcystin
  18. contamination of Amaranthus hybridus, Brassica oleracea, and Lactuca sativa sold in markets: a case study of Zaria, Nigeria. Environmental Monitoring and Assessment, 191, 569. doi: 10.1007/s10661-019-7725-4
  19. Chorus, I., & Bartram, J. (1999). Toxic Cyanobacteria in Water: A guide to their public health consequences,
  20. monitoring and management. London: F & FN Spon.
  21. Djediat, C., Malecot, M., de Luze, A., Bernard, C., Puiseux-Dao, S., & Edery, M. (2010). Localization of
  22. microcystin-LR in medaka fish tissues after cyanotoxin gavage. Toxicon, 55, 531-535. doi: 10.1016/j.toxicon.2009.10.005
  23. Drobac, D., Tokodi, N., Lujic, J., Marinovic, Z., Subakov-Simic, G., Dulic, T., Vazic, T., Nybom, S.,
  24. Meriluoto, J., Codd, G. A., & Svircev, Z. (2016). Cyanobacteria and cyanotoxins in fishponds and their effects on fish tissue. Harmful Algae, 55, 66-76. doi: 10.1016/j.hal.2016.02.007
  25. Drozdzik, M., Groer, C., Penski, J., Lapczuk, J., Ostrowski, M., Lai, Y. R., Prasad, B., Unadkat, J. D.,
  26. Siegmund, W., & Oswald, S. (2014). Protein Abundance of Clinically Relevant Multidrug Transporters along the Entire Length of the Human Intestine. Molecular Pharmaceutics, 11, 3547-3555. doi: 10.1021/mp500330y
  27. Duan, Y. F., Xiong, D. L., Wang, Y., Dong, H. B., Huang, J. H., & Zhang, J. S. (2020). Effects of Microcystis
  28. aeruginosa and microcystin-LR on intestinal histology, immune response, and microbial community in Litopenaeus vannamei. Environmental Pollution, 265, 114774. doi: 10.1016/j.envpol.2020.114774
  29. Feng, H., Clara, T., Huang, F. Y., Wei, J., & Yang, F. (2019). Identification and characterization of the
  30. dominant Microcystis sp. cyanobacteria detected in Lake Dong Ting, China. Journal of Toxicology and Environmental Health-Part a-Current Issues, 82, 1143-1150. doi: 10.1080/15287394.2019.1700604
  31. Ferreira, M. F., Oliveira, V. M., Oliveira, R., da Cunha, P. V., Grisolia, C. K., & Pires, O. R. (2010).
  32. Histopathological effects of D-Leu(1) Microcystin-LR variants on liver, skeletal muscle and intestinal tract of Hypophthalmichthys molitrix (Valenciennes, 1844). Toxicon, 55, 1255-1262. doi: 10.1016/j.toxicon.2010.01.016
  33. Feurstein, D., Holst, K., Fischer, A., & Dietrich, D. R. (2009). Oatp-associated uptake and toxicity of
  34. microcystins in primary murine whole brain cells. Toxicol Appl Pharmacol, 234, 247-255. doi: 10.1016/j.taap.2008.10.011
  35. Filipic, M., Zegura, B., Sedmak, B., Žnidaršič, I., Milutinovic, A., & Suput, D. (2007). Subchronic exposure
  36. of rats to sublethal dose of microcystin-YR induces DNA damage in multiple organs. Radiology and Oncology, 41, 15-22. doi: 10.2478/v10019-007-0003-z
  37. Fischer, W. J., Altheimer, S., Cattori, V., Meier, P. J., Dietrich, D. R., & Hagenbuch, B. (2005). Organic anion
  38. transporting polypeptides expressed in liver and brain mediate uptake of microcystin. Toxicol Appl Pharmacol, 203, 257-263. doi: 10.1016/j.taap.2004.08.012
  39. Fischer, W. J., & Dietrich, D. R. (2000). Toxicity of the cyanobacterial cyclic heptapeptide toxins microcystin-
  40. LR and -RR in early life-stages of the African clawed frog (Xenopus laevis). Aquatic Toxicology, 49, 189-198. doi: 10.1016/s0166-445x(99)00079-x
  41. Francy, D. S., Brady, A. M. G., Stelzer, E. A., Cicale, J. R., Hackney, C., Dalby, H. D., Struffolino, P., &
  42. Dwyer, D. F. (2020). Predicting microcystin concentration action-level exceedances resulting from cyanobacterial blooms in selected lake sites in Ohio. Environmental Monitoring and Assessment, 192, 513. doi: 10.1007/s10661-020-08407-x
  43. Gaudin, J., Huet, S., Jarry, G., & Fessard, V. (2008). In vivo DNA damage induced by the cyanotoxin
  44. microcystin-LR: Comparison of intra-peritoneal and oral administrations by use of the comet assay. Mutation Research-Genetic Toxicology and Environmental Mutagenesis, 652, 65-71. doi: 10.1016/j.mrgentox.2007.10.024
  45. Greer, B., Meneely, J. P., & Elliott, C. T. (2018). Uptake and accumulation of Microcystin-LR based on
  46. exposure through drinking water: An animal model assessing the human health risk. Scientific Reports, 8. doi: 10.1038/s41598-018-23312-7
  47. Grube, M., Kock, K., Oswald, S., Draber, K., Meissner, K., Eckel, L., Bohm, M., Felix, S. B., Vogelgesang,
  48. S., Jedlitschky, G., Siegmund, W., Warzok, R., & Kroemer, H. K. (2006). Organic anion transporting polypeptide 2B1 is a high-affinity transporter for atorvastatin and is expressed in the human heart. Clinical Pharmacology & Therapeutics, 80, 607-620. doi: 10.1016/j.clpt.2006.09.010
  49. Guo, J., Wei, J., Huang, F., Massey, I.Y., Luo, J., & Yang, F. (2021). Optimization of microcystin
  50. biodegradation by bacterial community YFMCD4 using response surface method. Chemosphere, 274, 129897. doi: https://doi.org/10.1016/j.chemosphere.2021.129897
  51. Hahn, S., Ferschke, M., & Groeneveld, M. (2019). The Digestive Tract, Part 7: Large Intestine - Anatomy,
  52. Physiology and Microbiota. Ernahrungs Umschau, 66, M425-M431. doi: 10.4455/eu.2019.027
  53. Huguet, A., Henri, J., Petitpas, M., Hogeveen, K., & Fessard, V. (2013). Comparative Cytotoxicity, Oxidative
  54. Stress, and Cytokine Secretion Induced by Two Cyanotoxin Variants, Microcystin LR and RR, in Human Intestinal Caco-2 Cells. Journal of Biochemical and Molecular Toxicology, 27, 253-258. doi: 10.1002/jbt.21482
  55. IARC. (2010). Ingested Nitrate and Nitrite, and Cyanobacterial Peptide Toxins. World Health Organization,
  56. International Agency for Research on Cancer. Lyon, France.
  57. Ito, E., Kondo, F., & Harada, K. (2001). Intratracheal administration of microcystin-LR, and its distribution.
  58. Toxicon, 39, 265-271.
  59. Ito, E., Kondo, F., & Harada, K. I. (2000). First report on the distribution of orally administered microcystin-
  60. LR in mouse tissue using an immunostaining method. Toxicon, 38, 37-48. doi: http://dx.doi.org/10.1016/S0041-0101(99)00084-7
  61. Jia, J., Luo, W., Lu, Y., & Giesy, J. P. (2014). Bioaccumulation of microcystins (MCs) in four fish species
  62. from Lake Taihu, China: assessment of risks to humans. Sci Total Environ, 487, 224-232. doi: 10.1016/j.scitotenv.2014.04.037
  63. Jochimsen, E. M., Carmichael, W. W., An, J. S., Cardo, D. M., Cookson, S. T., Holmes, C. E., Antunes, M.
  64. B., de Melo Filho, D. A., Lyra, T. M., Barreto, V. S., Azevedo, S. M., &. Jarvis, W. R. (1998). Liver failure and death after exposure to microcystins at a hemodialysis center in Brazil. N Engl J Med, 338, 873-878. doi: 10.1056/nejm199803263381304
  65. Kastl, A. J., Terry, N. A., Wu, G. D., & Albenberg, L. G. (2020). The Structure and Function of the Human
  66. Small Intestinal Microbiota: Current Understanding and Future Directions. Cellular and Molecular Gastroenterology and Hepatology, 9, 33-45. doi: 10.1016/j.jcmgh.2019.07.006
  67. Li, J., Chen, C. Y., Zhang, T. Z., Liu, W. J., Wang, L., Chen, Y. Y., Wu, L., Hegazy, A. M., El-Sayed, A. F.,
  68. & Zhang, X. Z. (2019). mu Evaluation of microcystin-LR absorption using an in vivo intestine model and its effect on zebrafish intestine. Aquatic Toxicology, 206, 186-194. doi: 10.1016/j.aquatox.2018.11.014
  69. Li, X. Y., and Ma, J. G., 2017. Mitochondria and lysosomes play a key role in HepG2 cell apoptosis induced
  70. by microcystin-LR. Toxin Reviews, 36, 63-72. doi: 10.1080/15569543.2016.1230133
  71. Liu, P., Wei, J., Yang, K., Massey, I. Y., Guo, J., Zhang, C., & Yang, F. (2018). Isolation, molecular
  72. Identification and characterization of a unique toxic cyanobacterium Microcystis sp. found in Hunan Province, China. Journal of toxicology and environmental health. Part A, 81, 1142-1149. doi: 10.1080/15287394.2018.1532716
  73. MacKintosh, C., Beattie, K. A., Klumpp, S., Cohen, P., & Codd, G. A. (1990). Cyanobacterial microcystin-
  74. LR is a potent and specific inhibitor of protein phosphatases 1 and 2A from both mammals and higher plants. FEBS Lett, 264, 187-192.
  75. Massey, I. Y., Al osman, M., & Yang, F. (2020). An overview on cyanobacterial blooms and toxins
  76. Production: their occurrence and influencing factors. Toxin Reviews, 1-21. doi: 10.1080/15569543.2020.1843060
  77. Massey, I. Y., & Yang, F. (2020). A mini review on microcystins and bacterial degradation. Toxins, 12, 268.
  78. doi: 10.3390/toxins12040268
  79. Middendorp, S., Schneeberger, K., Wiegerinck, C. L., Mokry, M., Akkerman, R. D. L., van Wijngaarden, S.,
  80. Clevers, H., & Nieuwenhuis, E. E. S. (2014). Adult Stem Cells in the Small Intestine Are Intrinsically Programmed with Their Location-Specific Function. Stem Cells, 32, 1083-1091. doi: 10.1002/stem.1655
  81. Mohamed, Z., Ahmed, Z., Bakr, A., Hashem, M., & Alamri, S. (2020). Detection of free and bound
  82. microcystins in tilapia fish from Egyptian fishpond farms and its related public health risk assessment. Journal of Consumer Protection and Food Safety, 15, 37-47. doi: 10.1007/s00003-019-01254-0
  83. Ni, W. M., Zhang, J. Y., & Luo, Y. (2015). Microcystin accumulation in bighead carp (Aristichthys nobilis)
  84. during a Microcystis-dominated bloom and risk assessment of the dietary intake in a fish pond in China. Environmental Science and Pollution Research, 24, 8894-8902. doi: 10.1007/s11356-015-4974-9
  85. Oswald, S. (2019). Organic Anion Transporting Polypeptide (OATP) transporter expression, localization and
  86. function in the human intestine. Pharmacology & Therapeutics, 195, 39-53. doi: 10.1016/j.pharmthera.2018.10.007
  87. Pires, J. O. R., de Oliveira, N. B., Bosque, R. J., Nice, F. M. F., Aurelio da Silva, V. M., Martins, M., A. C.,
  88. Correia de Santana, C. J., & Castro, M. S. (2018). Histopathological Evaluation of the Exposure by Cyanobacteria Cultive Containing d-Leu(1) Microcystin-LR on Lithobates catesbeianus Tadpoles. Toxins, 10, 318. doi: 10.3390/toxins10080318
  89. Preeti, T., Hariharan, G., & Rajarajeswari, G. R. (2016). Histopathological and biochemical effects of
  90. cyanobacterial cells containing microcystin-LR on Tilapia fish. Water and Environment Journal, 30, 135-142. doi: 10.1111/wej.12169
  91. Qu, M., Nida, A., Kong, Y., Du, H. H., Xiao, G. S., & Wang, D. Y. (2019). Nanopolystyrene at predicted
  92. environmental concentration enhances microcystin-LR toxicity by inducing intestinal damage in Caenorhabditis elegans. Ecotoxicology and Environmental Safety, 183, 109568. doi: 10.1016/j.ecoenv.2019.109568
  93. Romo, S., Fernandez, F., Ouahid, Y., & Baron-Sola, A. (2012). Assessment of microcystins in lake water and
  94. fish (Mugilidae, Liza sp.) in the largest Spanish coastal lake. Environmental Monitoring and Assessment, 184, 939-949. doi: 10.1007/s10661-011-2011-0
  95. Sarkar, S., Kimono, D., Albadrani, M., Seth, R. K., Busbee, P., Alghetaa, H., Porter, D. E., Scott, G. I., Brooks,
  96. B., Nagarkatti, M., Nagarkatti, P., & Chatterjee, S. (2019). Environmental microcystin targets the microbiome and increases the risk of intestinal inflammatory pathology via NOX2 in underlying murine model of Nonalcoholic Fatty Liver Disease. Scientific Reports, 9. doi: 10.1038/s41598-019-45009-1
  97. Sedan, D., Laguens, M., Copparoni, G., Aranda, J. O., Giannuzzi, L., Marra, C. A., & Andrinolo, D. (2015).
  98. Hepatic and intestine alterations in mice after prolonged exposure to low oral doses of Microcystin-LR. Toxicon, 104, 26-33. doi: 10.1016/j.toxicon.2015.07.011
  99. Sivonen, K., & Jones, G. (1999). Cyanobacterial toxins. In: Chorus, I., Bartram, J. (Eds.), Toxic Cyanobacteria
  100. in Water. A Guide to Their Public Health Consequences, Monitoring and Management. E and FN Spon, London, 41-111.
  101. Su, R. C., Blomquist, T. M., Kleinhenz, A. L., Khalaf, F. K., Dube, P., Lad, A., Breidenbach, J. D.,
  102. Mohammed, C. J., Zhang, S., Baum, C. E., Malhotra, D., Kennedy, D. J., & Haller, S. T. (2019). Exposure to the Harmful Algal Bloom (HAB) Toxin Microcystin-LR (MC-LR) Prolongs and Increases Severity of Dextran Sulfate Sodium (DSS)-Induced Colitis. Toxins, 11, 371. doi: 10.3390/toxins11060371
  103. Su, R. C., Meyers, C. M., Warner, E. A., Garcia, J. A., Refsnider, J. M., Lad, A., Breidenbach, J. D.,
  104. Modyanov, N., Malhotra, D., Haller, S. T., & Kennedy, D. J. (2020). Harmful Algal Bloom Toxicity inLithobates catesbeianaTadpoles. Toxins, 12, 378. doi: 10.3390/toxins12060378
  105. Svircev, Z., Lalic, D., Bojadzija Savic, G., Tokodi, N., Drobac Backovic, D., Chen, L., Meriluoto, J., & Codd,
  106. G. A. (2019). Global geographical and historical overview of cyanotoxin distribution and cyanobacterial poisonings. Arch Toxicol., 93, 2429-2481. doi: 10.1007/s00204-019-02524-4
  107. Thakkar, N., Lockhart, A. C., & Lee, W. (2015). Role of Organic Anion-Transporting Polypeptides (OATPs)
  108. in Cancer Therapy. Aaps Journal, 17, 535-545. doi: 10.1208/s12248-015-9740-x
  109. Tokodi, N., Drobac, D., Meriluoto, J., Lujic, J., Marinovic, Z., Vazic, T., Vazic, T., Nybom, S., Simeunovic,
  110. J., Dulic, T., Lazic, G., Petrovic, T., Vukovic-Gacic, B., Sunjog, K., Kolarevic, S., Kracun-Kolarevic, M., Subakov-Simic, G., Miljanovic, B., Codd, G. A., & Svircev, Z. (2018). Cyanobacterial effects in Lake Ludos, Serbia - Is preservation of a degraded aquatic ecosystem justified? Science of the Total Environment, 635, 1047-1062. doi: 10.1016/j.scitotenv.2018.04.177
  111. Trinchet, I., Djediat, C., Huet, H., Dao, S. P., & Edery, M. (2011). Pathological modifications following sub-
  112. chronic exposure of medaka fish (Oryzias latipes) to microcystin-LR. Reproductive Toxicology, 32, 329-340. doi: 10.1016/j.reprotox.2011.07.006
  113. Vesterkvist, P. S. M., Misiorek, J. O., Spoof, L. E. M., Toivola, D. M., & Meriluoto, J. A. O. (2012).
  114. Comparative Cellular Toxicity of Hydrophilic and Hydrophobic Microcystins on Caco-2 Cells. Toxins, 4, 1008-1023. doi: 10.3390/toxins4111008
  115. Vishy, M. (2019). Anatomy of the caecum, appendix and colon. Basic Science, 28, 1-6. doi:
  116. DOI:https://doi.org/10.1016/j.mpsur.2019.10.017
  117. Volk, N., & Lacy, B. (2017). Anatomy and Physiology of the Small Bowel. Gastrointestinal endoscopy clinics
  118. of North America, 27, 1-13. doi: 10.1016/j.giec.2016.08.001
  119. Wei, J., Huang, F., Feng, H., Massey, I. Y., Clara, T., Long, D., Cao, Y., Luo, J., & Yang, F. (2021).
  120. Characterization and Mechanism of Linearized-Microcystinase Involved in Bacterial Degradation of Microcystins. Frontiers in Microbiology, 12, 646084. doi: 10.3389/fmicb.2021.646084
  121. Wen, C., Zheng, S. L., Yang, Y., Li, X. Y., Chen, J. H., Wang, X. Y., Feng, X. L., Yang, F. (2019). Effects of
  122. microcystins-LR on genotoxic responses in human intestinal epithelial cells (NCM460). Journal of Toxicology and Environmental Health-Part a-Current Issues, 82, 1113-1119 doi: 10.1080/15287394.2019.1698498
  123. WHO. (1998). Cyanobacterial toxins: Microcystin-LR. Guidelines for drinking water quality. World Health
  124. Organization, Geneva, Switzerland.
  125. Wu, J., Huang, H., Wang, R., Li, Y., Liu, H., Yuan, L., Wang, Y., Du, X., Zhuang, D., Cheng, X., & Zhang,
  126. H. (2018). Effects of MC-LR exposure on inflammation factors and apoptosis-related proteins in small intestine of mice. Life Science Journal, 15, 32-36. doi: doi:10.7537/marslsj150718.05
  127. Xia, H., Son, T., Wang, L., Jiang, L. S., Zhou, Q. T., Wang, W. M., Liu, L. G., Yang, P. H., Zhang, X. Z.
  128. (2018). Effects of dietary toxic cyanobacteria and ammonia exposure on immune function of blunt snout bream (Megalabrama amblycephala). Fish & Shellfish Immunology, 78, 383-391. doi: 10.1016/j.fsi.2018.04.023
  129. Xu, S., Yi, X., Liu, W., Zhang, C., Massey, I. Y., Yang, F., & Tian, L. (2020). A review of nephrotoxicity of
  130. microcystins. Toxins, 12, 693. doi: 10.3390/toxins12110693
  131. Yang, F., Huang, F., Feng, H., Wei, J., Massey, I. Y., Liang, G., Zhang, F., Yin, L., Kacew, S., Zhang, X., &
  132. Pu, Y. (2020). A complete route for biodegradation of potentially carcinogenic cyanotoxin microcystin-LR in a novel indigenous bacterium. Water Research, 174, 115638. doi: https://doi.org/10.1016/j.watres.2020.115638
  133. Yuan, J. L., Gu, Z. M., Zheng, Y., Zhang, Y. Y., Gao, J. C., Chen, S., & Wang, Z. Z. (2016). Accumulation
  134. and detoxification dynamics of microcystin-LR and antioxidant responses in male red swamp crayfish Procambarus clarkii. Aquatic Toxicology, 177, 8-18. doi: 10.1016/j.aquatox.2016.05.004
  135. Žegura, B., Volčič, M., Lah, T. T., & Filipič, M. (2008). Different sensitivities of human colon
  136. adenocarcinoma (CaCo-2), astrocytoma (IPDDC-A2) and lymphoblastoid (NCNC) cell lines to microcystin-LR induced reactive oxygen species and DNA damage. Toxicon, 52, 518-525. doi: http://doi.org/10.1016/j.toxicon.2008.06.026
  137. Zeller, P., Clement, M., & Fessard, V. (2011). Similar uptake profiles of microcystin-LR and -RR in an in
  138. vitro human intestinal model. Toxicology, 290, 7-13. doi: 10.1016/j.tox.2011.08.005
  139. Zhang, D., Xie, P., Liu, Y., Chen, J., & Liang, G. (2007b). Bioaccumulation of the hepatotoxic microcystins
  140. in various organs of a freshwater snail from a subtropical Chinese lake, Taihu Lake, with dense toxic Microcystis blooms. Environ Toxicol Chem, 26, 171-176.
  141. Zhang, H., Zhang, J., Hong, Y., & Chen, Y. (2007a). Evaluation of organ distribution of microcystins in the
  142. freshwater phytoplanktivorous fish Hypophthalmichthys molitrix. Journal of Zhejiang University-Science B, 8, 116-120. doi: 10.1631/jzus.2007.B0116
  143. Zhang, Y., Li, Z., Kholodkevich, S., Sharov, A., Feng, Y., Ren, N., & Sun, K. (2020). Microcystin-LR-induced
  144. changes of hepatopancreatic transcriptome, intestinal microbiota, and histopathology of freshwater crayfish (Procambarus clarkii). The Science of the total environment, 711, 134549. doi: 10.1016/j.scitotenv.2019.134549
  145. Zhou, Y., Xu, X. P., Yu, B. B., & Yu, G. (2017). Characterization of in vitro effects of microcystin-LR on
  146. intestinal epithelial cells. Environmental Toxicology, 32, 1539-1547. doi: 10.1002/tox.22375
  147. Zikova, A., Lorenz, C., Lutz, I., Pflugmacher, S., & Kloas, W. (2013). Physiological responses of Xenopus
  148. laevis tadpoles exposed to cyanobacterial biomass containing microcystin-LR. Aquatic Toxicology, 128, 25-33. doi: 10.1016/j.aquatox.2012.11.004