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1

González-Blanco, Carlos, Felipe Augusto Dörr, Renata Albuquerque, Janice Onuki i Ernani Pinto. "Alternative Isolation Protocol for Desulfo and Zwitterionic Cylindrospermopsin Alkaloids and Comparison of Their Toxicity in HepG2 Cells". Molecules 25, nr 13 (2.07.2020): 3027. http://dx.doi.org/10.3390/molecules25133027.

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The term cylindrospermopsins (CYNs) refers to a structurally related class of cyanobacterial metabolites comprised of a tricyclic guanidine group and a hydroxymethyluracil moiety. Most reports in environmental aquatic samples refer to cylindrospermopsin (CYN), and reports on other CYN alkaloids are scarce, due, in part, to a lack of versatile isolation protocols. Thus, using commercially available solid phase extraction (SPE) cartridges, we optimized an isolation protocol for the complete recovery of CYN, 7-deoxy-cylindrospermopsin (7D-CYN) and 7-deoxy-desulfo-cylindrospermopsin (7D-desulfo-CYN) from the same aliquot. The isolation protocol was adaptable depending on the nature of the sample (solid biomass, culture broth or environmental water sample) and tolerates up to 4 L of dense culture broth or 400 mg of lyophilized biomass. To quantitate the CYN alkaloids, we validated an LC-DAD-MS2 method, which takes advantage of the UV absorption of the uracil group (λ 262 nm). Using electrospray ionization (ESI) in a positive ion mode, the high-resolution MS1 data confirms the presence of the protonated alkaloids, and the MS2 fragment assignment is reported as complementary proof of the molecular structure of the CYNs. We isolated three CYN alkaloids with different water solubility using the same lyophilized sample, with a purity that ranged from 95% to 99%. The biological activity of the purified CYNs, along with a synthetic degradation product of CYN (desulfo-cylindrospermopsin), was evaluated by assessing necrosis and apoptosis in vitro using flow cytometry. CYN’s lethal potency in HepG2 cells was greater than the other analogs, due to the presence of all four functional groups: guanidine, uracil, C-7 hydroxyl and the sulfate residue.
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2

Chichova, Mariela, Oskan Tasinov, Milena Shkodrova, Milena Mishonova, Iliyana Sazdova, Bilyana Ilieva, Dilyana Doncheva-Stoimenova i in. "New Data on Cylindrospermopsin Toxicity". Toxins 13, nr 1 (8.01.2021): 41. http://dx.doi.org/10.3390/toxins13010041.

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Cylindrospermopsin (CYN) is a widely spread cyanotoxin that can occur in fresh water and food. This research aims to investigate CYN toxicity by studying the effects of drinking 0.25 nM of CYN-contaminated water from a natural source, and of the direct application of moderate concentrations of CYN on different animal targets. The chosen structures and activities are rat mitochondria inner membrane permeability, mitochondrial ATP synthase (ATPase) and rat liver diamine oxidase (DAO) activities (EC 1.4.3.22.), the force of the contraction of an excised frog heart preparation with functional innervation, and the viability of a human intestinal epithelial cell line (HIEC-6). The oral exposure to CYN decreased the reverse (hydrolase) activity of rat liver ATPase whereas its short-term, in vitro application was without significant effect on this organelle, DAO activity, heart contractions, and their neuronal regulation. The application of CYN reduced HIEC-6 cells’ viability dose dependently. It was concluded that CYN is moderately toxic for the human intestinal epithelial cells, where the regeneration of the epithelial layer can be suppressed by CYN. This result suggests that CYN may provoke pathological changes in the human gastrointestinal tract.
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3

Chichova, Mariela, Oskan Tasinov, Milena Shkodrova, Milena Mishonova, Iliyana Sazdova, Bilyana Ilieva, Dilyana Doncheva-Stoimenova i in. "New Data on Cylindrospermopsin Toxicity". Toxins 13, nr 1 (8.01.2021): 41. http://dx.doi.org/10.3390/toxins13010041.

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Cylindrospermopsin (CYN) is a widely spread cyanotoxin that can occur in fresh water and food. This research aims to investigate CYN toxicity by studying the effects of drinking 0.25 nM of CYN-contaminated water from a natural source, and of the direct application of moderate concentrations of CYN on different animal targets. The chosen structures and activities are rat mitochondria inner membrane permeability, mitochondrial ATP synthase (ATPase) and rat liver diamine oxidase (DAO) activities (EC 1.4.3.22.), the force of the contraction of an excised frog heart preparation with functional innervation, and the viability of a human intestinal epithelial cell line (HIEC-6). The oral exposure to CYN decreased the reverse (hydrolase) activity of rat liver ATPase whereas its short-term, in vitro application was without significant effect on this organelle, DAO activity, heart contractions, and their neuronal regulation. The application of CYN reduced HIEC-6 cells’ viability dose dependently. It was concluded that CYN is moderately toxic for the human intestinal epithelial cells, where the regeneration of the epithelial layer can be suppressed by CYN. This result suggests that CYN may provoke pathological changes in the human gastrointestinal tract.
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4

Seawright, Alan, Ross Norris, Glen Shaw, Michael Moore i Vanessa Burgess. "Toxicity of the cyanobacterial toxin, cylindrospermopsin in mammals". Toxicology 148, nr 1 (lipiec 2000): 75–76. http://dx.doi.org/10.1016/s0300-483x(00)90314-7.

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5

Shaw, G., i P. K. S. Lam. "Health aspects of freshwater cyanobacterial toxins". Water Supply 7, nr 2 (1.07.2007): 193–203. http://dx.doi.org/10.2166/ws.2007.054.

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Cyanobacterial (blue-green algal) toxins are known to cause poisoning in humans, livestock and wild animals. Based on their toxic mechanisms, cyanobacterial toxins are generally categorized as neurotoxins, hepatotoxins or cytotoxins. The acute oral toxicities of these toxins vary substantially, with the saxitoxins being the most toxic having an LD50 of 60 μg/kg. By comparison, the acute oral LD50 for microcystin LR (the most toxic congener) and cylindrospermopsin are approximately 5,000 to 10,000 μg/kg and 6,000 μg/kg over 5 days, respectively. There are well known adverse health issues of cyanobacterial toxin poisonings. The most serious health consequences have occurred in Brazil with the reported deaths of people from gastrointestinal symptoms associated with exposure to microcystins and cylindrospermopsin. Increased number of symptoms has also been reported via exposure to cyanobacterial toxins through water-based recreational activities. Toxins may also be present in drinking water and thus guideline values are necessary to protect the health of the population. Guideline values are available for microcystins but not for saxitoxins, cylindrospermopsin or deoxycylindrospermopsin. Considerable research is being undertaken currently on more fully understanding the mechanisms of toxicity of cylindrospermopsin to enable relevant guidelines to be established.
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6

Pierangelini, Mattia, Rati Sinha, Anusuya Willis, Michele A. Burford, Philip T. Orr, John Beardall i Brett A. Neilan. "Constitutive Cylindrospermopsin Pool Size in Cylindrospermopsis raciborskii under Different Light and CO2Partial Pressure Conditions". Applied and Environmental Microbiology 81, nr 9 (27.02.2015): 3069–76. http://dx.doi.org/10.1128/aem.03556-14.

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ABSTRACTCylindrospermopsin (CYN) and 7-deoxy-cylindrospermopsin (dCYN) are potent hepatotoxic alkaloids produced by numerous species of cyanobacteria, including the freshwaterCylindrospermopsis raciborskii.C. raciborskiiis an invasive cyanobacterium, and the study of how environmental parameters drive CYN production has received significant interest from water managers and health authorities. Light and CO2affect cell growth and physiology in photoautotrophs, and these are potential regulators of cyanotoxin biosynthesis. In this study, we investigated how light and CO2affect CYN and dCYN pool size as well as the expression of the key genes,cyrAandcyrK, involved in CYN biosynthesis in a toxicC. raciborskiistrain. For cells growing at different light intensities (10 and 100 μmol photons m−2s−1), we observed that the rate of CYN pool size production (μCYN) was coupled to the cell division rate (μc) during batch culture. This indicated that CYN pool size under our experimental conditions is constant and cell quotas of CYN (QCYN) and dCYN (QdCYN) are fixed. Moreover, a lack of correlation between expression ofcyrAand total CYN cell quotas (QCYNs) suggests that the CYN biosynthesis is regulated posttranscriptionally. Under elevated CO2(1,300 ppm), we observed minor effects on QCYNand no effects on expression ofcyrAandcyrK. We conclude that the CYN pool size is constitutive and not affected by light and CO2conditions. Thus,C. raciborskiibloom toxicity is determined by the absolute abundance ofC. raciborskiicells within the water column and the relative abundance of toxic and nontoxic strains.
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7

Falfushynska, Halina, Nadiia Kasianchuk, Eduard Siemens, Eliana Henao i Piotr Rzymski. "A Review of Common Cyanotoxins and Their Effects on Fish". Toxics 11, nr 2 (25.01.2023): 118. http://dx.doi.org/10.3390/toxics11020118.

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Global warming and human-induced eutrophication drive the occurrence of various cyanotoxins in aquatic environments. These metabolites reveal diversified mechanisms of action, encompassing cyto-, neuro-, hepato-, nephro-, and neurotoxicity, and pose a threat to aquatic biota and human health. In the present paper, we review data on the occurrence of the most studied cyanotoxins, microcystins, nodularins, cylindrospermopsin, anatoxins, and saxitoxins, in the aquatic environment, as well as their potential bioaccumulation and toxicity in fish. Microcystins are the most studied among all known cyanotoxins, although other toxic cyanobacterial metabolites are also commonly identified in aquatic environments and can reveal high toxicity in fish. Except for primary toxicity signs, cyanotoxins adversely affect the antioxidant system and anti-/pro-oxidant balance. Cyanotoxins also negatively impact the mitochondrial and endoplasmic reticulum by increasing intracellular reactive oxygen species. Furthermore, fish exposed to microcystins and cylindrospermopsin exhibit various immunomodulatory, inflammatory, and endocrine responses. Even though cyanotoxins exert a complex pressure on fish, numerous aspects are yet to be the subject of in-depth investigation. Metabolites other than microcystins should be studied more thoroughly to understand the long-term effects in fish and provide a robust background for monitoring and management actions.
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8

Chernoff, N., D. J. Hill, I. Chorus, D. L. Diggs, H. Huang, D. King, J. R. Lang i in. "Cylindrospermopsin toxicity in mice following a 90-d oral exposure". Journal of Toxicology and Environmental Health, Part A 81, nr 13 (25.04.2018): 549–66. http://dx.doi.org/10.1080/15287394.2018.1460787.

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9

Evans, Daniel M., Jack Hughes, Leigh F. Jones, Patrick J. Murphy, Halina Falfushynska, Oksana Horyn, Inna M. Sokolova, Jeppe Christensen, Simon J. Coles i Piotr Rzymski. "Elucidating cylindrospermopsin toxicity via synthetic analogues: An in vitro approach". Chemosphere 234 (listopad 2019): 139–47. http://dx.doi.org/10.1016/j.chemosphere.2019.06.021.

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10

Aklakur, Md, Subham Bakli, Ashutosh D. Deo, D. K. Singh i G. H. Pailan. "Cyanobacteria toxicity in aquaculture system and its impact on fish physiology". Journal of Aquaculture & Marine Biology 12, nr 1 (2023): 28–33. http://dx.doi.org/10.15406/jamb.2023.12.00353.

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Algae and some Cyanobacteria, being a core part of primary production, act as a food organism for many fishes and other aquatic organisms. But they can also be responsible for fish kill or illness. Review on Cyanobacteria effect on fish growth, survival, and recruitment is the need of the hour. The mechanisms of toxicity of cyanotoxins and their toxic metabolites in fish have been scarcely covered. The effects may be sublethal on growth, physiology, survival, recruitment, and in long run, it may have a role in the fish’s adaptive response to abiotic and other biotic stressors. Around 46 species from genera of Microcystis, Cylindrospermopsis, Synechococcus, Anabaena, Lyngbya, Oscillatoria, etc. have been shown to cause toxic effects in aquatic system. The bloom of these cyanobacteria is primarily associated with altered temperature and nutrient load in water bodies due to effluents from municipal discharge and aquaculture. Their acute or chronic toxic effects may vary depending on the species, type of toxin produced, and concentration. The various cyanotoxins are grouped as hepatotoxins like microcystin, nodularin cylindrospermopsin, neurotoxins; like anatoxins, homoanatoxins, dermatotoxins; like aplysiatoxin, debromoaplysiatoxins, lyngbyatoxins, and pyrogenic component; like lipopolysaccharides (LPS). The concentration of the specific cyanotoxin in the fish body and the water along with other factors such as the length of exposure, fish metabolic processes, water parameters like dissolved oxygen and temperature, are likely to impact cyanotoxin toxicity in freshwater fish. The impact of such toxicity may be reflected on the individual species level, ecosystem level, and even at the culture system level.
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11

Berry, John P., Patrick D. L. Gibbs, Michael C. Schmale i Martin L. Saker. "Toxicity of cylindrospermopsin, and other apparent metabolites from Cylindrospermopsis raciborskii and Aphanizomenon ovalisporum, to the zebrafish (Danio rerio) embryo". Toxicon 53, nr 2 (luty 2009): 289–99. http://dx.doi.org/10.1016/j.toxicon.2008.11.016.

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12

Fastner, J., R. Heinze, A. R. Humpage, U. Mischke, G. K. Eaglesham i I. Chorus. "Cylindrospermopsin occurrence in two German lakes and preliminary assessment of toxicity and toxin production of Cylindrospermopsis raciborskii (Cyanobacteria) isolates". Toxicon 42, nr 3 (wrzesień 2003): 313–21. http://dx.doi.org/10.1016/s0041-0101(03)00150-8.

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13

Banker, R., S. Carmeli, M. Werman, B. Teltsch, R. Porat i A. Sukenik. "Uracil Moiety is Required for Toxicity of the Cyanobacterial Hepatotoxin Cylindrospermopsin". Journal of Toxicology and Environmental Health, Part A 62, nr 4 (23.02.2001): 281–88. http://dx.doi.org/10.1080/009841001459432.

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14

Adamski, Michal, Paweł Żmudzki, Jan Bialczyk, Ariel Kaminski, Ewelina Chrapusta-Srebrny, Beata Bober i Kornelia Duchnik. "Decomposition products of cylindrospermopsin – a cyanotoxin produced by Raphidiopsis raciborskii (Woloszynska)". Oceanological and Hydrobiological Studies 48, nr 3 (25.09.2019): 227–35. http://dx.doi.org/10.2478/ohs-2019-0020.

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Abstract Toxins produced by cyanobacteria (cyanotoxins) and released into water have become a serious problem worldwide due to the increasing morbidity and mortality of living organisms they have caused. The ability to synthesize the cytotoxic alkaloid cylindrospermopsin (CYN) has been demonstrated in several freshwater species of cyanobacteria. CYN is highly chemically stable under environmental factors and decomposes only under alkaline conditions, where it forms derivatives. The toxicity potential of the decomposition products formed at pH 10 combined with high temperature (100°C) or UV-B irradiation (36 μmol m−2 s−1) has been research based on the crustacean Thamnocephalus platyurus (Thamnotoxkit FTM) and bacteria Vibrio fischeri (Deltatox® II) bioassays. This paper is a continuation and completion of our previous experiments and the obtained results showed that the applied conditions contributed to the decomposition of the CYN molecule to non-toxic products and its structural modifications by separating the uracil ring or/and the sulfate group from the tricyclic guanidine moiety, leading to a reduction in its toxicity. To the best of our knowledge, this is the first report describing the toxicity of CYN decomposition products formed under alkaline conditions combined with boiling temperature or UV-B irradiation.
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15

Chong, M. W. K., B. S. F. Wong, P. K. S. Lam, G. R. Shaw i A. A. Seawright. "Toxicity and uptake mechanism of cylindrospermopsin and lophyrotomin in primary rat hepatocytes". Toxicon 40, nr 2 (luty 2002): 205–11. http://dx.doi.org/10.1016/s0041-0101(01)00228-8.

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Poniedziałek, Barbara, Piotr Rzymski i Krzysztof Wiktorowicz. "Toxicity of cylindrospermopsin in human lymphocytes: Proliferation, viability and cell cycle studies". Toxicology in Vitro 28, nr 5 (sierpień 2014): 968–74. http://dx.doi.org/10.1016/j.tiv.2014.04.015.

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Almeida, Cristhiano Sibaldo de, Andrea Caroline Costa de Arruda, Erika Caldas de Queiroz, Haline Tereza Matias de Lima Costa, Patrícia Fernandes Barbosa, Telma Maria Araújo Moura Lemos, Cláudia Nunes Oliveira, Ernani Pinto, Aline Schwarz i Paula Kujbida. "Oral exposure to cylindrospermopsin in pregnant rats: Reproduction and foetal toxicity studies". Toxicon 74 (listopad 2013): 127–29. http://dx.doi.org/10.1016/j.toxicon.2013.08.051.

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Diez-Quijada, Leticia, Maria del Monte Benítez-González, María Puerto, Angeles Jos i Ana M. Cameán. "Immunotoxic Effects Induced by Microcystins and Cylindrospermopsin: A Review". Toxins 13, nr 10 (8.10.2021): 711. http://dx.doi.org/10.3390/toxins13100711.

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Cyanotoxin occurrence is gaining importance due to anthropogenic activities, climate change and eutrophication. Among them, Microcystins (MCs) and Cylindrospermopsin (CYN) are the most frequently studied due to their ubiquity and toxicity. Although MCs are primary classified as hepatotoxins and CYN as a cytotoxin, they have been shown to induce deleterious effects in a wide range of organs. However, their effects on the immune system are as yet scarcely investigated. Thus, to know the impact of cyanotoxins on the immune system, due to its importance in organisms’ homeostasis, is considered of interest. A review of the scientific literature dealing with the immunotoxicity of MCs and CYN has been performed, and both in vitro and in vivo studies have been considered. Results have confirmed the scarcity of reports on the topic, particularly for CYN. Decreased cell viability, apoptosis or altered functions of immune cells, and changed levels and mRNA expression of cytokines are among the most common effects reported. Underlying mechanisms, however, are still not yet fully elucidated. Further research is needed in order to have a full picture of cyanotoxin immunotoxicity.
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Diez-Quijada, Leticia, María Puerto, Daniel Gutiérrez-Praena, Maria V. Turkina, Alexandre Campos, Vitor Vasconcelos, Ana M. Cameán i Ángeles Jos. "In Vitro Toxicity Evaluation of Cyanotoxins Cylindrospermopsin and Microcystin-LR on Human Kidney HEK293 Cells". Toxins 14, nr 7 (23.06.2022): 429. http://dx.doi.org/10.3390/toxins14070429.

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Cyanotoxins are secondary metabolites produced by different types of cyanobacteria. Among them, Cylindrospermopsin (CYN) and Microcystins (MCs) stand out due to their wide geographical distribution and toxicity in various organs, including the kidney, which is involved in their distribution and elimination. However, the renal toxicity caused by CYN and MCs has hardly been studied. The aim of this work was to assess the cytotoxicity effects caused by CYN and MC-LR in the renal cell line HEK293, and for the first time, the influence of CYN on the gene expression of selected genes in these cells by quantitative real-time PCR (qRT-PCR). CYN caused an upregulation in the gene expression after exposure to the highest concentration (5 µg/mL) and the longest time of exposure (24 h). Moreover, shotgun proteomic analysis was used to assess the molecular responses of HEK293 cells after exposure to the individuals and combinations of CYN + MC-LR. The simultaneous exposure to both cyanotoxins caused a greater number of alterations in protein expression compared to single toxins, causing changes in the cellular, lipid and protein metabolism and in protein synthesis and transport. Further studies are needed to complete the toxicity molecular mechanisms of both CYN and MC-LR at the renal level.
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Poniedziałek, Barbara, Piotr Rzymski i Jacek Karczewski. "The role of the enzymatic antioxidant system in cylindrospermopsin-induced toxicity in human lymphocytes". Toxicology in Vitro 29, nr 5 (sierpień 2015): 926–32. http://dx.doi.org/10.1016/j.tiv.2015.03.023.

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Martínez-Ruiz, Erika Berenice, Myriel Cooper, Munir A. Al-Zeer, Jens Kurreck, Lorenz Adrian i Ulrich Szewzyk. "Manganese-oxidizing bacteria form multiple cylindrospermopsin transformation products with reduced human liver cell toxicity". Science of The Total Environment 729 (sierpień 2020): 138924. http://dx.doi.org/10.1016/j.scitotenv.2020.138924.

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Froscio, Suzanne M., Andrew R. Humpage, Philip C. Burcham i Ian R. Falconer. "Cylindrospermopsin-induced protein synthesis inhibition and its dissociation from acute toxicity in mouse hepatocytes". Environmental Toxicology 18, nr 4 (2003): 243–51. http://dx.doi.org/10.1002/tox.10121.

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BITTENCOURT-OLIVEIRA, MARIA DO CARMO, VIVIANE PICCIN-SANTOS, ARIADNE N. MOURA, NÍSIA K. C. ARAGÃO-TAVARES i MICHELINE K. CORDEIRO-ARAÚJO. "Cyanobacteria, microcystins and cylindrospermopsin in public drinking supply reservoirs of Brazil". Anais da Academia Brasileira de Ciências 86, nr 1 (marzec 2014): 297–310. http://dx.doi.org/10.1590/0001-3765201302512.

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Brazil has a history of blooms and contamination of freshwater systems by cyanobacterial toxins. The monitoring relevance of toxins from cyanobacteria in reservoirs for public supply is notorious given its high toxicity to mammals, included humans beings. The most recurrent toxins in Brazilian water bodies are microcystins (MC). However, the recent record of cylindrospermopsin (CYN) in northeastern Brazil, Pernambuco state, alerts us to the possibility that this could be escalating. This study reports occurrence of MC and CYN, quantified with ELISA, in 10 reservoirs, devoted to public drinking supply in northeastern Brazil. The composition and quantification of the cyanobacteria community associated with these water bodies is also presented. From 23 samples investigated for the presence of MC, and CYN, 22 and 8 out were positive, respectively. Considering the similarity of the cyanobacteria communities found in reservoirs from Pernambuco, including toxin-producing species associated to MC and CYN, we suggest that geographic spreading can be favored by these factors. These issues emphasize the need for increased monitoring of MC and CYN in drinking supply reservoirs in Brazil.
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de la Cruz, Armah A., Anastasia Hiskia, Triantafyllos Kaloudis, Neil Chernoff, Donna Hill, Maria G. Antoniou, Xuexiang He i in. "A review on cylindrospermopsin: the global occurrence, detection, toxicity and degradation of a potent cyanotoxin". Environmental Science: Processes & Impacts 15, nr 11 (2013): 1979. http://dx.doi.org/10.1039/c3em00353a.

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Rogers, E. H., R. D. Zehr, M. I. Gage, A. R. Humpage, I. R. Falconer, M. Marr i N. Chernoff. "The cyanobacterial toxin, cylindrospermopsin, induces fetal toxicity in the mouse after exposure late in gestation". Toxicon 49, nr 6 (maj 2007): 855–64. http://dx.doi.org/10.1016/j.toxicon.2006.12.009.

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Sukenik, A., M. Reisner, S. Carmeli i M. Werman. "Oral toxicity of the cyanobacterial toxin cylindrospermopsin in mice: Long-term exposure to low doses". Environmental Toxicology 21, nr 6 (2006): 575–82. http://dx.doi.org/10.1002/tox.20220.

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Kinnear, S. H. W., L. D. Fabbro, L. J. Duivenvoorden i E. M. A. Hibberd. "Multiple-organ toxicity resulting from cylindrospermopsin exposure in tadpoles of the cane toad (Bufo marinus)". Environmental Toxicology 22, nr 6 (2007): 550–58. http://dx.doi.org/10.1002/tox.20299.

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Chernoff, N., E. H. Rogers, R. D. Zehr, M. I. Gage, D. E. Malarkey, C. A. Bradfield, Y. Liu i in. "Toxicity and recovery in the pregnant mouse after gestational exposure to the cyanobacterial toxin, cylindrospermopsin". Journal of Applied Toxicology 31, nr 3 (8.10.2010): 242–54. http://dx.doi.org/10.1002/jat.1586.

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Metcalf, J. S., J. Lindsay, K. A. Beattie, S. Birmingham, M. L. Saker, A. K. Törökné i G. A. Codd. "Toxicity of cylindrospermopsin to the brine shrimp Artemia salina: comparisons with protein synthesis inhibitors and microcystins". Toxicon 40, nr 8 (sierpień 2002): 1115–20. http://dx.doi.org/10.1016/s0041-0101(02)00105-8.

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Scarlett, Kendall R., Sujin Kim, Lea M. Lovin, Saurabh Chatterjee, J. Thad Scott i Bryan W. Brooks. "Global scanning of cylindrospermopsin: Critical review and analysis of aquatic occurrence, bioaccumulation, toxicity and health hazards". Science of The Total Environment 738 (październik 2020): 139807. http://dx.doi.org/10.1016/j.scitotenv.2020.139807.

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31

Runnegar, M. T., S. M. Kong, Y. Z. Zhong, J. L. Ge i S. C. Lu. "The Role of Glutathione in the Toxicity of a Novel Cyanobacterial Alkaloid Cylindrospermopsin in Cultured Rat Hepatocytes". Biochemical and Biophysical Research Communications 201, nr 1 (maj 1994): 235–41. http://dx.doi.org/10.1006/bbrc.1994.1694.

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Choi, Jae-won, Jae-heon Jang, Sun-hong Lee i Mi-ae Yoon. "Determination of Cylindrospermopsin in Surface and Treated Water using Liquid Chromatography-Tandem Mass Spectrometry". Journal of Environmental Analysis, Health and Toxicology 25, nr 2 (30.06.2022): 71–76. http://dx.doi.org/10.36278/jeaht.25.2.71.

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Cylindrospermopsin (CYN) is an emerging freshwater cyanobacterial toxin, and its reports on toxicity toward the human liver and kidney tissues has drawn a lot of attention. An appropriate analytical method is necessary to determine the presence of this emerging cyanobacterial toxin in water resources including drinking water; therefore, it is necessary to develop a sensitive analytical method for CYN detection. In this study, we developed a simple and sensitive analytical method for CYN detection using liquid chromatography-tandem mass spectrometry (LC-MS/MS) using direct injection. The method was validated for linearity of calibration, limit of detection, limit of quantitation, accuracy, and precision. The limit of detection and quantitation were in the range of 0.029 μg/L and 0.091 μg/L, respectively. Accuracy and precision were also obtained within an acceptable range. The optimized method was used to measure the concentrations of CYN in the surface water from each weir areas of the Geum River, Nakdong River. Additionally, this method was applied to samples of drinking water obtained from the treatment plants of the Geum River, Nakdong River for each process.
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Czyżewska, Wanda, Marlena Piontek i Katarzyna Łuszczyńska. "The Occurrence of Potential Harmful Cyanobacteria and Cyanotoxins in the Obrzyca River (Poland), a Source of Drinking Water". Toxins 12, nr 5 (28.04.2020): 284. http://dx.doi.org/10.3390/toxins12050284.

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Harmful cyanobacteria and their cyanotoxins may contaminate drinking water resources and their effective control remains challenging. The present study reports on cyanobacterial blooms and associated cyanotoxins in the Obrzyca River, a source of drinking water in Poland. The river was examined from July to October 2019 and concentrations of microcystins, anatoxin-a, and cylindrospermopsin were monitored. The toxicity of water samples was also tested using an ecotoxicological assay. All studied cyanotoxins were detected with microcystins revealing the highest levels. Maximal microcystin concentrations (3.97 μg/L) were determined in September at Uście point, exceeding the provisional guideline. Extracts from Uście point, where the dominant species were Dolichospermum flos-aquae (August), Microcystis aeruginosa (September), and Planktothrix agardhii (October), were toxic for Dugesia tigrina Girard. Microcystin concentrations (MC-LR and MC-RR) were positively correlated with cyanobacteria biovolume. Analysis of the chemical indicators of water quality has shown relationships between them and microcystins as well as cyanobacteria abundance.
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34

Cordeiro, Rita, Rúben Luz, Joana Vilaverde, Vitor Vasconcelos, Amélia Fonseca i Vítor Gonçalves. "Distribution of Toxic Cyanobacteria in Volcanic Lakes of the Azores Islands". Water 12, nr 12 (2.12.2020): 3385. http://dx.doi.org/10.3390/w12123385.

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Eutrophication and global climate change gather advantageous conditions for cyanobacteria proliferation leading to bloom formation and cyanotoxin production. In the Azores, eutrophication is a major concern, mainly in lakes where fertilizers and organic matter discharges have increased nutrient concentration. In this study, we focused on understanding the influence of environmental factors and lake characteristics on (i) cyanobacteria diversity and biomass and (ii) the presence of toxic strains and microcystin, saxitoxin, anatoxin-a, and cylindrospermopsin cyanotoxin-producing genes. Fifteen lakes from the Azores Archipelago were sampled seasonally, environmental variables were recorded in situ, cyanobacteria were analyzed with microscopic techniques, and cyanotoxin-producing genes were targeted through conventional PCR. Statistical analysis (DistLM) showed that lake typology-associated variables (lake’s depth, area, and altitude) were the most explanatory variables of cyanobacteria biomass and cyanotoxin-producing genes presence, although trophic variables (chlorophyll a and total phosphorus) influence species distribution in each lake type. Our main results revealed higher cyanobacteria biomass/diversity, and higher toxicity risk in lakes located at lower altitudes, associated with deep anthropogenic pressures and eutrophication scenarios. These results emphasize the need for cyanobacteria blooms control measures, mainly by decreasing anthropogenic pressures surrounding these lakes, thus decreasing eutrophication. We also highlight the potential for microcystin, saxitoxin, and anatoxin-a production in these lakes, hence the necessity to implement continuous mitigation protocols to avoid environmental and public health toxicity events.
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Díez-Quijada, Leticia, Ana I. Prieto, María Puerto, Ángeles Jos i Ana M. Cameán. "In Vitro Mutagenic and Genotoxic Assessment of a Mixture of the Cyanotoxins Microcystin-LR and Cylindrospermopsin". Toxins 11, nr 6 (4.06.2019): 318. http://dx.doi.org/10.3390/toxins11060318.

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The co-occurrence of various cyanobacterial toxins can potentially induce toxic effects different than those observed for single cyanotoxins, as interaction phenomena cannot be discarded. Moreover, mixtures are a more probable exposure scenario. However, toxicological information on the topic is still scarce. Taking into account the important role of mutagenicity and genotoxicity in the risk evaluation framework, the objective of this study was to assess the mutagenic and genotoxic potential of mixtures of two of the most relevant cyanotoxins, Microcystin-LR (MC-LR) and Cylindrospermopsin (CYN), using the battery of in vitro tests recommended by the European Food Safety Authority (EFSA) for food contaminants. Mixtures of 1:10 CYN/MC-LR (CYN concentration in the range 0.04–2.5 µg/mL) were used to perform the bacterial reverse-mutation assay (Ames test) in Salmonella typhimurium, the mammalian cell micronucleus (MN) test and the mouse lymphoma thymidine-kinase assay (MLA) on L5178YTk± cells, while Caco-2 cells were used for the standard and enzyme-modified comet assays. The exposure periods ranged between 4 and 72 h depending on the assay. The genotoxicity of the mixture was observed only in the MN test with S9 metabolic fraction, similar to the results previously reported for CYN individually. These results indicate that cyanobacterial mixtures require a specific (geno)toxicity evaluation as their effects cannot be extrapolated from those of the individual cyanotoxins.
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36

Ahari, Hamed, Bahareh ‎. Nowruzi, Amir Ali Anvar i Samaneh Jafari Porzani. "The Toxicity Testing of Cyanobacterial Toxins In vivo and In vitro by Mouse Bioassay: A Review". Mini-Reviews in Medicinal Chemistry 22, nr 8 (maj 2022): 1131–51. http://dx.doi.org/10.2174/1389557521666211101162030.

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: Different biological methods based on bioactivity are available to detect cyanotoxins, including neurotoxicity, immunological interactions, hepatotoxicity, cytotoxicity, and enzymatic activity. The mouse bioassay is the first test employed in laboratory cultures, cell extracts, and water bloom materials to detect toxins. It is also used as a traditional method to estimate the LD50. Concerning the ease of access and low cost, it is the most common method for this purpose. In this method, a sample is injected intraperitoneally into adult mice, and accordingly, they are assayed and monitored for about 24 hours for toxic symptoms. The toxin can be detected using this method from minutes to a few hours; its type, e.g., hepatotoxin, neurotoxin, etc., can also be determined. However, this method is nonspecific, fails to detect low amounts, and cannot distinguish between homologues. Although the mouse bioassay is gradually replaced with new chemical and immunological methods, it is still the main technique to detect the bioactivity and efficacy of cyanotoxins using LD50 determined based on the survival time of animals exposed to the toxin. In addition, some countries oppose animal use in toxicity studies. However, high cost, ethical considerations, low-sensitivity, non-specificity, and prolonged processes persuade researchers to employ chemical and functional analysis techniques. The qualitative and quantitative analyses, as well as high specificity and sensitivity, are among the advantages of cytotoxicity tests to investigate cyanotoxins. The present study aimed at reviewing the results obtained from in vitro and in vivo investigations of the mouse bioassay to detect cyanotoxins, including microcystins, cylindrospermopsin, saxitoxins, etc.
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Flores-Rojas, Nelida Cecilia, i Maranda Esterhuizen. "Uptake and Effects of Cylindrospermopsin: Biochemical, Physiological and Biometric Responses in The Submerged Macrophyte Egeria densa Planch". Water 12, nr 11 (26.10.2020): 2997. http://dx.doi.org/10.3390/w12112997.

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Cylindrospermopsin (CYN) is being detected in surface waters more commonly and frequently worldwide. This stable, extracellular cyanotoxin causes protein synthesis inhibition, thus posing a risk to aquatic biota, including macrophytes, which serve as primary producers. Nevertheless, data regarding the effects caused by environmental concentrations of CYN is still limited. In the presented study, the uptake of CYN at environmental concentrations by the submerged macrophyte Egeria densa was investigated. Bioaccumulation, changes in the plant biomass, as well as shoot-length were assessed as responses. Variations in the cellular H2O2 levels, antioxidative enzyme activities, as well as concentrations and ratios of the photosynthetic pigments were also measured. E. densa removed 54% of CYN within 24 h and up to 68% after 336 h; however, CYN was not bioaccumulated. The antioxidative enzyme system was activated by CYN exposure. Pigment concentrations decreased with exposure but normalized after 168 h. The chlorophyll a to b ratio increased but normalized quickly thereafter. Carotenoids and the ratio of carotenoids to total chlorophylls increased after 96 h suggesting participation in the antioxidative system. Growth stimulation was observed. The ability to remove CYN and resistance to CYN toxicity within 14 days proved E. densa as suitable for phytoremediation; nonetheless, prolonged exposure (32 days) resulted in adverse effects related to CYN uptake, which needs to be studied further.
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38

Gutiérrez-Praena, Daniel, Silvia Pichardo, Ángeles Jos i Ana María Cameán. "Toxicity and glutathione implication in the effects observed by exposure of the liver fish cell line PLHC-1 to pure cylindrospermopsin". Ecotoxicology and Environmental Safety 74, nr 6 (wrzesień 2011): 1567–72. http://dx.doi.org/10.1016/j.ecoenv.2011.04.030.

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Pappas, Dimitris, Manthos Panou, Ioannis-Dimosthenis S. Adamakis, Spyros Gkelis i Emmanuel Panteris. "Beyond Microcystins: Cyanobacterial Extracts Induce Cytoskeletal Alterations in Rice Root Cells". International Journal of Molecular Sciences 21, nr 24 (17.12.2020): 9649. http://dx.doi.org/10.3390/ijms21249649.

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Microcystins (MCs) are cyanobacterial toxins and potent inhibitors of protein phosphatases 1 (PP1) and 2A (PP2A), which are involved in plant cytoskeleton (microtubules and F-actin) organization. Therefore, studies on the toxicity of cyanobacterial products on plant cells have so far been focused on MCs. In this study, we investigated the effects of extracts from 16 (4 MC-producing and 12 non-MC-producing) cyanobacterial strains from several habitats, on various enzymes (PP1, trypsin, elastase), on the plant cytoskeleton and H2O2 levels in Oryza sativa (rice) root cells. Seedling roots were treated for various time periods (1, 12, and 24 h) with aqueous cyanobacterial extracts and underwent either immunostaining for α-tubulin or staining of F-actin with fluorescent phalloidin. 2,7-dichlorofluorescein diacetate (DCF-DA) staining was performed for H2O2 imaging. The enzyme assays confirmed the bioactivity of the extracts of not only MC-rich (MC+), but also MC-devoid (MC−) extracts, which induced major time-dependent alterations on both components of the plant cytoskeleton. These findings suggest that a broad spectrum of bioactive cyanobacterial compounds, apart from MCs or other known cyanotoxins (such as cylindrospermopsin), can affect plants by disrupting the cytoskeleton.
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40

Magrann, Tracey, Howard Meredith D. A., Sutula Martha, Boskovic Danilo S., Hayes William K. i Dunbar Stephen G. "Screening Assessment of Cyanobacteria and Cyanotoxins in Southern California Lentic Habitats". Environmental Management and Sustainable Development 4, nr 2 (9.09.2015): 91. http://dx.doi.org/10.5296/emsd.v4i2.8036.

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<p class="emsd"><span lang="EN-GB">Harmful bloom-forming cyanobacteria (CyanoHABs) and associated toxins are increasingly prevalent world-wide. We</span><span lang="EN-GB"> conducted a screening-level study to determine if cyanobacteria and associated cyanotoxins were present in Southern California coastal lakes, ponds, and seasonally tidal lagoons. We evaluated waterbody nutrient status and physiochemical parameters, land use, waterbody type, and habitat type, to determine their utility as screening factors for risk of CyanoHAB blooms. </span><span lang="EN-GB">One-time grab samples were collected from 30 sites during July</span><span lang="EN-GB">–</span><span lang="EN-GB">September 2009. Samples were analyzed for phytoplankton taxonomic composition, nutrients, other physiochemical parameters, and three cyanotoxins: m</span><span lang="EN-GB">icrocystins (MCY), anatoxin-a, and cylindrospermopsin</span><span lang="EN-GB">. </span><span lang="EN-GB">Cyanobacteria was the predominant taxonomic group in most water bodies in this study, and <em>Microcystis</em> spp. was the predominant genus in 96% of the study sites. Cyanobacteria were equally prevalent among coastal lagoons, depressional wetlands, and lakes in this study. We detected MCY in high concentrations in 10% of our sites</span><span lang="EN-GB">, but neither anatoxin-a nor cylindrospermopsin were detected. All of the MCY-positive sites exceeded California action levels for recreational use and World Health Organization (WHO) guidance for human health effects. The prevalence of <em>Microcystis </em>spp. from all study sites indicates a high potential for MCY in these water bodies, although the one-time toxin grab samples likely underestimated the overall toxicity of these sites. Landscape variables, such as developed land use and dominant habitat type, were not found to be predictive indicators of cyanobacterial dominance. However, because cyanobacteria become consistently dominant when chlorophyll-a levels exceed 15 µg L<sup>-1</sup>, chlorophyll-a can serve as a significant predictor of MCY. </span></p>
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41

Chernoff, N., E. H. Rogers, R. D. Zehr, M. I. Gage, G. S. Travlos, D. E. Malarkey, A. Brix, J. E. Schmid i D. Hill. "The Course of Toxicity in the Pregnant Mouse After Exposure to the Cyanobacterial Toxin Cylindrospermopsin: Clinical Effects, Serum Chemistries, Hematology, and Histopathology". Journal of Toxicology and Environmental Health, Part A 77, nr 17 (29.07.2014): 1040–60. http://dx.doi.org/10.1080/15287394.2014.919838.

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42

Lindsay, J., J. S. Metcalf i G. A. Codd. "Protection against the toxicity of microcystin-LR and cylindrospermopsin in Artemia salina and Daphnia spp. by pre-treatment with cyanobacterial lipopolysaccharide (LPS)". Toxicon 48, nr 8 (grudzień 2006): 995–1001. http://dx.doi.org/10.1016/j.toxicon.2006.07.036.

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43

Antosiak, Adam, Nada Tokodi, Robert Maziarz, Mikołaj Kokociński, Agnieszka Brzozowska, Wojciech Strzałka, Agnieszka Katarzyna Banaś, Anusuya Willis i Dariusz Dziga. "Different Gene Expression Response of Polish and Australian Raphidiopsis raciborskii Strains to the Chill/Light Stress". Applied Sciences 10, nr 16 (6.08.2020): 5437. http://dx.doi.org/10.3390/app10165437.

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R. raciborskii is known for growing under wide ranges of temperature and light. In temperate regions, however, low temperature and high light may serve as a stressful condition for invading tropical populations. The genetic basis of R. raciborskii’s adaptation to this combination of stresses are unknown. In this study, the growth rate and the expression of genes that may be crucial in the response to the chill/light stress of two R. raciborskii strains (differing in their climatic origin and toxicity) exposed to low temperature and high light were examined. Results showed that AMU-DH-30, a non CYN (cylindrospermopsin) producing strain isolated from the temperate region, exhibited under stress the upregulation of genes involved in the protein translation (rbp1, nusG, hflX), membrane fluidity (desA), photosynthetic activity (ccr2 and ftsH), and the accumulation of compatible solutes (asd). In contrast, a CYN producing Australian strain CS-505 was not able to adapt quickly and to continue growth during stress conditions. Intriguingly, CS-505 and AMU-DH-30 had a similar ability to resume growth when the stress conditions subsided. Moreover, in strain CS-505 the cyrB gene was significantly upregulated under the stress conditions. The presented results shed new light on the possible mechanisms involved in the response of R.raciborskii to chill/light stress.
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44

Brandenburg, Karen, Laura Siebers, Joost Keuskamp, Thomas G. Jephcott i Dedmer B. Van de Waal. "Effects of Nutrient Limitation on the Synthesis of N-Rich Phytoplankton Toxins: A Meta-Analysis". Toxins 12, nr 4 (1.04.2020): 221. http://dx.doi.org/10.3390/toxins12040221.

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Eutrophication has played a major role in the worldwide increase of harmful algal blooms (HABs). Higher input of key nutrients, such as nitrogen (N) and phosphorus (P), can stimulate the growth of harmful algal species in freshwater, estuarine, and coastal marine ecosystems. Some HAB-forming taxa, particularly several cyanobacteria and dinoflagellate species, are harmful through the production of N-rich toxins that have detrimental effects on the environment and human health. Here, we test how changes in nutrient availability affect N-rich toxin synthesis in cyanobacteria and dinoflagellates using a meta-analysis approach. Overall, N-rich toxin content showed an increase with P limitation, while it tended to decrease with N limitation, but we also observed substantial variation in responses both within and across genera and toxin groups. For instance, in response to N limitation, microcystin content varied from a 297% decrease up to a 273% increase, and paralytic shellfish poisoning (PSP) toxin content varied from a 204% decrease to an 82% increase. Cylindrospermopsin, produced by N2-fixing cyanobacteria, showed no clear direction in response to nutrient limitation, and cellular contents of this compound may thus vary independently of nutrient fluctuations. Our results confirm earlier reported stoichiometric regulation of N-rich phytoplankton toxins, showing increased toxin content with an increase in cellular N:P ratios, and vice versa. Thus, changes in N-rich toxin content largely follow the changes in relative cellular N content. Consequently, although nutrient limitation may limit bloom biomass and thereby bloom toxicity, our results warn that P limitation can cause accumulation of cellular toxins and thus lead to unexpected increases in bloom toxicity.
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45

Kucała, Małgorzata, Michał Saładyga i Ariel Kaminski. "Phytoremediation of CYN, MC-LR and ANTX-a from Water by the Submerged Macrophyte Lemna trisulca". Cells 10, nr 3 (21.03.2021): 699. http://dx.doi.org/10.3390/cells10030699.

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Cyanotoxins are harmful to aquatic and water-related organisms. In this study, Lemna trisulca was tested as a phytoremediation agent for three common cyanotoxins produced by bloom-forming cyanobacteria. Cocultivation of L. trisulca with Dolichospermum flos-aquae in BG11 medium caused a release of the intracellular pool of anatoxin-a into the medium and the adsorption of 92% of the toxin by the plant—after 14 days, the total amount of toxin decreased 3.17 times. Cocultivation with Raphidopsis raciborskii caused a 2.77-time reduction in the concentration of cylindrospermopsin (CYN) in comparison to the control (62% of the total pool of CYN was associated with the plant). The greatest toxin limitation was noted for cocultivation with Microcystis aeruginosa. After two weeks, the microcystin-LR (MC-LR) concentration decreased more than 310 times. The macrophyte also influenced the growth and development of cyanobacteria cells. Overall, 14 days of cocultivation reduced the biomass of D. flos-aquae, M. aeruginosa, and R. raciborskii by 8, 12, and 3 times, and chlorophyll a concentration in comparison to the control decreased by 17.5, 4.3, and 32.6 times, respectively. Additionally, the macrophyte stabilized the electrical conductivity (EC) and pH values of the water and affected the even uptake of cations and anions from the medium. The obtained results indicate the biotechnological potential of L. trisulca for limiting the development of harmful cyanobacterial blooms and their toxicity.
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46

Humpage, A. R., i I. R. Falconer. "Oral toxicity of the cyanobacterial toxin cylindrospermopsin in male Swiss albino mice: Determination of no observed adverse effect level for deriving a drinking water guideline value". Environmental Toxicology 18, nr 2 (2003): 94–103. http://dx.doi.org/10.1002/tox.10104.

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Karadžić, Vesna, Jelena Jovanović, Snežana Živković-Perišić, Dragana Jovanović i Milan Milenković. "Hepatotoxic products of cyanobacteria and their toxicological effects". Glasnik javnog zdravlja 95, nr 1 (2021): 54–72. http://dx.doi.org/10.5937/gjz2101054k.

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Chronic human exposure to water contaminated with hepatotoxic cyanobacterial compounds (cyanotoxins) can lead to an increased incidence of hepatocellular carcinoma or other forms of liver disease. Humans can be exposed to cyanotoxins through ingestion, inhalation and dermal contact, i.e. by using contaminated drinking water, recreational water, water used for hemodialysis or via food. Among hepatotoxic cyanotoxins, cyclic peptides microcystins and nodularin should be emphasized, as well as the tricyclic alkaloid cylindrospermopsin. In addition, the existence of a new hepatotoxic cyanobacterial secondary metabolite, called limnotrixin, has been investigated in recent years. Due to the different chemical structures of these cyanotoxins, mechanisms of their toxic effects also differ. Globally, hepatotoxins are the most common cyanobacterial toxins and, among them, microcystins are the most frequently detected during cyanobacterial blooms and also the most extensively studied. The latter is also the case in the Republic of Serbia, where cases of cyanobacterial blooms in water bodies used for water supply are mostly related to species that are potential microcystin producers (e.g. representatives of the genera Microcystis and Planktothrix). Additionally, microcystins are the only group of hepatotoxic cyanotoxins for which regular monitoring has been established in our country, which primarily refers to the water bodies used as water supply sources. However, since there is an increased frequency of cyanobacterial blooming, both worldwide and in our country, it is very important to monitor potential risks and understand the toxicity and potential carcinogenicity of hepatotoxic products of cyanobacteria, which was the main aim of this study
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48

Saker, Martin L. "Distribution and toxicity of Cylindrospermopsis raciborskii (Cyanobacteria) in Portuguese freshwaters". Limnetica 23, nr 1 (15.06.2004): 145–52. http://dx.doi.org/10.23818/limn.23.12.

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Hawkins, Peter R., Nimal R. Chandrasena, Gary J. Jones, Andrew R. Humpage i Ian R. Falconer. "Isolation and toxicity of Cylindrospermopsis raciborskii from an ornamental lake". Toxicon 35, nr 3 (marzec 1997): 341–46. http://dx.doi.org/10.1016/s0041-0101(96)00185-7.

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Rzymski, Piotr, Agnieszka Brygider i Mikołaj Kokociński. "On the occurrence and toxicity of Cylindrospermopsis raciborskii in Poland". Limnological Review 17, nr 1 (1.03.2017): 23–29. http://dx.doi.org/10.1515/limre-2017-0003.

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AbstractCylindrospermopsis raciborskiiwhich belongs to the order of Nostocales has continuously been at the centre of interest of various research groups owing to its great ecological plasticity, wide distribution and potential to produce different metabolites known to be harmful for humans and animals. Over recent decades, Polish strains ofC.raciborskiihave also been studied with regard to these issues. The present paper is a brief review of the present state of knowledge respecting the occurrence and toxicity of this species with emphasis on Polish strains, and indicates potential directions for future research.
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