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In Vivo and In Vitro Toxicity Testing of Cyanobacterial Toxins: A Mini-Review

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Reviews of Environmental Contamination and Toxicology Volume 258

Part of the book series: Reviews of Environmental Contamination and Toxicology ((RECT,volume 258))

Abstract

Harmful cyanobacterial blooms are increasing and becoming a worldwide concern as many bloom-forming cyanobacterial species can produce toxic metabolites named cyanotoxins. These include microcystins, saxitoxins, anatoxins, nodularins, and cylindrospermopsins, which can adversely affect humans, animals, and the environment. Different methods to assess these classes of compounds in vitro and in vivo include biological, biochemical, molecular, and physicochemical techniques. Furthermore, toxic effects not attributable to known cyanotoxins can be observed when assessing bloom material. In order to determine exposures to cyanotoxins and to monitor compliance with drinking and bathing water guidelines, it is necessary to have reliable and effective methods for the analysis of these compounds. Many relatively simple low-cost methods can be employed to rapidly evaluate the potential hazard. The main objective of this mini-review is to describe the assessment of toxic cyanobacterial samples using in vitro and in vivo bioassays. Newly emerging cyanotoxins, the toxicity of analogs, or the interaction of cyanobacteria and cyanotoxins with other toxicants, among others, still requires bioassay assessment. This review focuses on some biological and biochemical assays (MTT assay, Immunohistochemistry, Micronucleus Assay, Artemia salina assay, Daphnia magna test, Radionuclide recovery, Neutral red cytotoxicity and Comet assay, Enzyme-Linked Immunosorbent Assay (ELISA), Annexin V-FITC assay and Protein Phosphatase Inhibition Assay (PPIA)) for the detection and measurement of cyanotoxins including microcystins, cylindrospermopsins, anatoxin-a, saxitoxins, and nodularins. Although most bioassay analyses often confirm the presence of cyanotoxins at low concentrations, such bioassays can be used to determine whether some strains or blooms of cyanobacteria may produce other, as yet unknown toxic metabolites. This review also aims to identify research needs and data gaps concerning the toxicity assessment of cyanobacteria.

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Abbreviations

ATX:

Anatoxin-a

BMAA:

Beta-N-methylamino-l-alanine

BNCs:

Binucleated cells

CBPI:

Cytokinesis-block proliferation index

DAB:

2,4-diaminobutyric acid

FISH:

Fluorescence in situ hybridization

HBE:

Human bronchial epithelial cells

HPLC:

High performance liquid chromatography

i.p.:

Intraperitoneal injection

i.v.:

Intravenous injection

IHC:

Immunohistochemical techniques

LC/MS/MS:

Liquid chromatography tandem mass spectrometry

LOEC:

Lowest observed effect concentration

MC-YR, LR, RR:

Microcystins-YR, -LR and -RR

MNBC:

Micronucleated binucleated cells

MNi:

Micronuclei

MTT assay:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NODs:

Nodularins

NR:

Neutral Red

PP2A:

Protein phosphatase 2A

PPIA:

Protein phosphatase inhibition assay

ROS:

Reactive oxygen species

SCGE:

Single-cell gel electrophoresis

SRB:

Sulforhodamine B

STX:

Saxitoxin

References

  • Abend M, Rhein A, Gilbertz K-P, Blakely W, Van Beuningen D (1995) Correlation of micronucleus and apoptosis assays with reproductive cell death. Int J Radiat Biol 67:315–326

    CAS  Google Scholar 

  • Abramsson-Zetterberg L, Sundh UB, Mattsson R (2010) Cyanobacterial extracts and microcystin-LR are inactive in the micronucleus assay in vivo and in vitro. Mutat Res 699:5–10

    CAS  Google Scholar 

  • Almesjö L (2007) Filamentous cyanobacteria in the Baltic Sea-spatiotemporal patterns and nitrogen fixation. Systemekologiska institutionen, Stockholm, pp 1–32

    Google Scholar 

  • Andeden EE, Ozturk S, Aslim B (2018) Antiproliferative, neurotoxic, genotoxic and mutagenic effects of toxic cyanobacterial extracts. Interdiscip Toxicol 11:267–274

    CAS  Google Scholar 

  • Ariza RR, Keyse SM, Moggs JG, Wood RD (1996) Reversible protein phosphorylation modulates nucleotide excision repair of damaged DNA by human cell extracts. Nucleic Acids Res 24:433–440

    CAS  Google Scholar 

  • Babich H, Rosenberg D, Borenfreund E (1991) In vitro cytotoxicity studies with the fish hepatoma cell line, PLHC-1 (Poeciliopsis lucida). Ecotox Environ Safe 21:327–336

    CAS  Google Scholar 

  • Baker P, Humpage A (1994) Toxicity associated with commonly occurring cyanobacteria in surface waters of the Murray-Darling basin, Australia. Mar Freshw Res 45:773–786

    CAS  Google Scholar 

  • Bazin E, Mourot A, Humpage AR, Fessard V (2010) Genotoxicity of a freshwater cyanotoxin, cylindrospermopsin, in two human cell lines: Caco-2 and HepaRG. Environ Mol Mutagen 51(3):251–259

    Google Scholar 

  • Berry J, Lee E, Walton K, Wilson A, Bernal-Brooks F (2011) Microcystin production by a persistent cyanobacterial bloom in Lago de Pátzcuaro (Michoacán, Mexico), and apparent bioaccumulation of the toxin in small commercial catches of fish. Environ Toxicol Chem 30:1621–1628

    CAS  Google Scholar 

  • Birbeck JA, Westrick JA, O’Neill GM, Spies B, Szlag DC (2019) Comparative analysis of microcystin prevalence in Michigan lakes by online concentration LC/MS/MS and ELISA. Toxins 11:13

    CAS  Google Scholar 

  • Bolch CJ, Orr PT, Jones GJ, Blackburn SI (1999) Genetic, morphological, and toxicological variation among globally distributed strains of Nodularia (Cyanobacteria). J Phycol 35:339–355

    CAS  Google Scholar 

  • Borenfreund E, Puerner JA (1985) A simple quantitative procedure using monolayer cultures for cytotoxicity assays (HTD/NR-90). J Tissue Cult Methods 9:7–9

    Google Scholar 

  • Börner T, Dittmann E (2005) Molecular biology of cyanobacterial toxins. In: Harmful cyanobacteria. Springer, pp 25–40

    Google Scholar 

  • Brooks W, Codd G (1987) Distribution of Microcystis aeruginosa peptide toxin and interactions with hepatic microsomes in mice. Pharmacol Toxicol 60:187–191

    CAS  Google Scholar 

  • Brown A, Foss A, Miller MA, Gibson Q (2018) Detection of cyanotoxins (microcystins/nodularins) in livers from estuarine and coastal bottlenose dolphins (Tursiops truncatus) from Northeast Florida. Harmful Algae 76:22–34

    CAS  Google Scholar 

  • Buratti FM, Manganelli M, Vichi S, Stefanelli M, Scardala S, Testai E, Funari E (2017) Cyanotoxins: producing organisms, occurrence, toxicity, mechanism of action and human health toxicological risk evaluation. Arch Toxicol 91:1049–1130

    CAS  Google Scholar 

  • Burford MA, Carey CC, Hamilton DP, Huisman J, Paerl HW, Wood SA, Wulff A (2020) Perspective: advancing the research agenda for improving understanding of cyanobacteria in a future of global change. Harmful Algae 91:101601. https://doi.org/10.1016/j.hal.2019.04.004

    Article  CAS  Google Scholar 

  • Callieri C, Bertoni R, Contesini M, Bertoni F (2014) Lake level fluctuations boost toxic cyanobacterial “oligotrophic blooms”. PLoS One 9:e109526

    Google Scholar 

  • Campbell D, Lawton L, Beattie K, Codd G (1994) Comparative assessment of the specificity of the brine shrimp and microtox assays to hepatotoxic (microcystin-LR-containing) cyanobacteria. Environ Toxicol Water Qual 9:71–77

    CAS  Google Scholar 

  • Chatziefthimiou AD, Richer R, Rowles H, Powell JT, Metcalf JS (2014) Cyanotoxins as a potential cause of dog poisonings in desert environments. Vet Rec 174:484–485

    Google Scholar 

  • Chatziefthimiou AD, Metcalf JS, Glover WB, Banack SA, Dargham SR, Richer RA (2016) Cyanobacteria and cyanotoxins are present in drinking water impoundments and groundwater wells in desert environments. Toxicon 114:75–84

    CAS  Google Scholar 

  • Cheng A, Balczon R, Zuo Z, Koons JS, Walsh AH, Honkanen RE (1998) Fostriecin-mediated G2-M-phase growth arrest correlates with abnormal centrosome replication, the formation of aberrant mitotic spindles, and the inhibition of serine/threonine protein phosphatase activity. Cancer Res 58:3611–3619

    CAS  Google Scholar 

  • Chia MA, Kramer BJ, Jankowiak JG, Bittencourt-Oliveira MC, Gobler CJ (2019) The individual and combined effects of the cyanotoxins, anatoxin-a and microcystin-LR, on the growth, toxin production, and nitrogen fixation of prokaryotic and eukaryotic algae. Toxins 11:43

    CAS  Google Scholar 

  • Chong M, Wong B, Lam P, Shaw G, Seawright A (2002) Toxicity and uptake mechanism of cylindrospermopsin and lophyrotomin in primary rat hepatocytes. Toxicon 40:205–211

    CAS  Google Scholar 

  • Christensen VG, Khan E (2020) Freshwater neurotoxins and concerns for human, animal, and ecosystem health: a review of anatoxin-a and saxitoxin. Sci Total Environ 736:139515. https://doi.org/10.1016/j.scitotenv.2020.139515

    Article  CAS  Google Scholar 

  • Cohen Y, Gurevitz M (2006) The cyanobacteria—ecology, physiology and molecular genetics. The Prokaryotes 4:1074–1098

    Google Scholar 

  • Corbel S, Mougin C, Nélieu S, Delarue G, Bouaïcha N (2016) Evaluation of the transfer and the accumulation of microcystins in tomato (Solanum lycopersicum cultivar MicroTom) tissues using a cyanobacterial extract containing microcystins and the radiolabeled microcystin-LR (14C-MC-LR). Sci Total Environ 541:1052–1058

    CAS  Google Scholar 

  • Costa S (2005) Efeitos de saxitoxinas produzidas por Cylindrospermopsis raciborskii e de outras cianotoxinas sobre cladóceros (Branchiopoda) Programa de Pó s-graduaça o em Ciências Bioló gicas Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil (PhD thesis)

    Google Scholar 

  • Costa ID, Azevedo S, Senna P, Bernardo R, Costa S, Chellappa N (2006) Occurrence of toxin-producing cyanobacteria blooms in a Brazilian semiarid reservoir. Braz J Biol 66:211–219

    CAS  Google Scholar 

  • Cullen A, Pearson LA, Mazmouz R, Liu T, Soeriyadi AH, Ongley SE, Neilan BA (2019) Heterologous expression and biochemical characterisation of cyanotoxin biosynthesis pathways. Nat Prod Rep 36:1117–1136

    CAS  Google Scholar 

  • D'Anglada LV, Donohue JM, Strong J, Hawkins B (2015) Health effects support document for the cyanobacterial toxin cylindrospermopsin. US Environmental Protection Agency, Office of Water

    Google Scholar 

  • De Figueiredo DR, Azeiteiro UM, Esteves SM, Gonçalves FJ, Pereira MJ (2004) Microcystin-producing blooms—a serious global public health issue. Ecotox Environ Safe 59:151–163

    Google Scholar 

  • DeMott WR, Zhang QX, Carmichael WW (1991) Effects of toxic cyanobacteria and purified toxins on the survival and feeding of a copepod and three species of Daphnia. Limnol Oceanogr 36:1346–1357

    CAS  Google Scholar 

  • Dias E, Louro H, Pinto M, Santos T, Antunes S, Pereira P, Silva MJ (2014) Genotoxicity of microcystin-LR in in vitro and in vivo experimental models. Biomed Res Int 2014:9

    Google Scholar 

  • Ding W-X, Shen H-M, Zhu H-G, Lee B-L, Ong C-N (1999) Genotoxicity of microcystic cyanobacteria extract of a water source in China. Mutat Res 442:69–77

    CAS  Google Scholar 

  • Dixit RB, Patel AK, Toppo K, Nayaka S (2017) Emergence of toxic cyanobacterial species in the Ganga River, India, due to excessive nutrient loading. Ecol Indic 72:420–427

    CAS  Google Scholar 

  • Djediat C, Malécot M, de Luze A, Bernard C, Puiseux-Dao S, Edery M (2010) Localization of microcystin-LR in medaka fish tissues after cyanotoxin gavage. Toxicon 55:531–535

    CAS  Google Scholar 

  • Eaglesham GK et al (1999) Use of HPLC-MS/MS to monitor cylindrospermopsin, a blue–green algal toxin, for public health purposes. Environ Toxicol 14:151–154

    CAS  Google Scholar 

  • Eppley RM (1974) Sensitivity of brine shrimp (Artemia salina) to trichothecenes. J AOAC Int 57:618–620

    CAS  Google Scholar 

  • Falconer KJ (1986) The geometry of fractal sets, vol 85. Cambridge university press

    Google Scholar 

  • Fenech M (1997) The advantages and disadvantages of the cytokinesis-block micronucleus method. Mutat Res 392:11–18

    CAS  Google Scholar 

  • Fenech M (2000) The in vitro micronucleus technique. Mutat Res 455:81–95

    CAS  Google Scholar 

  • Fenech M, Morley AA (1986) Cytokinesis-block micronucleus method in human lymphocytes: effect of in vivo ageing and low dose X-irradiation. Mutat Res 161:193–198

    CAS  Google Scholar 

  • Fent K (2001) Fish cell lines as versatile tools in ecotoxicology: assessment of cytotoxicity, cytochrome P4501A induction potential and estrogenic activity of chemicals and environmental samples. Toxicology In Vitro 15(4–5):477–488

    Google Scholar 

  • Ferrão-Filho AS, Kozlowsky-Suzuki B (2011) Cyanotoxins: bioaccumulation and effects on aquatic animals. Mar Drugs 9:2729–2772

    Google Scholar 

  • Ferrão-Filho AS, Soares MCS, de Freitas MV, Azevedo SM (2009) Biomonitoring of cyanotoxins in two tropical reservoirs by cladoceran toxicity bioassays. Ecotox Environ Safe 72:479–489

    Google Scholar 

  • Filipič M, Žegura B, Sedmak B, Horvat-Žnidaršic I, Milutinovič A, Šuput D (2007) Subchronic exposure of rats to sublethal dose of microcystin-YR induces DNA damage in multiple organs. Radiol Oncol 41:15–22

    Google Scholar 

  • Fiore MF, de Lima ST, Carmichael WW, McKinnie SM, Chekan JR, Moore BS (2020) Guanitoxin, re-naming a cyanobacterial organophosphate toxin. Harmful Algae 92:101737

    Google Scholar 

  • Fischer WJ, Hitzfeld BC, Tencalla F, Eriksson JE, Mikhailov A, Dietrich DR (2000) Microcystin-LR toxicodynamics, induced pathology, and immunohistochemical localization in livers of blue-green algae exposed rainbow trout (Oncorhynchus mykiss). Toxicol Sci 54:365–373

    CAS  Google Scholar 

  • Fischer WJ, Garthwaite I, Miles CO, Ross KM, Aggen JB, Chamberlin AR, Towers NR, Dietrich DR (2001) Congener-independent immunoassay for microcystins and nodularins. Environ Sci Technol 35:4849–4856

    Google Scholar 

  • Freitas EC, Pinheiro C, Rocha O, Loureiro S (2014) Can mixtures of cyanotoxins represent a risk to the zooplankton? The case study of Daphnia magna Straus exposed to hepatotoxic and neurotoxic cyanobacterial extracts. Harmful Algae 31:143–152

    CAS  Google Scholar 

  • Froscio SM, Fanok S, Humpage AR (2009) Cytotoxicity screening for the cyanobacterial toxin cylindrospermopsin. J Toxicol 72:345–349

    CAS  Google Scholar 

  • Funari E, Testai E (2008) Human health risk assessment related to cyanotoxins exposure. Crit Rev Toxicol 38:97–125

    CAS  Google Scholar 

  • Funari E, Manganelli M, Sinisi L (2012) Impact of climate change on waterborne diseases. Annali dell'Istituto superiore di sanita 48:473–487

    Google Scholar 

  • Gaudin J, Huet S, Jarry G, Fessard V (2008) In vivo DNA damage induced by the cyanotoxin microcystin-LR: comparison of intra-peritoneal and oral administrations by use of the comet assay. Mutat Res 652:65–71

    CAS  Google Scholar 

  • Ghadouani A, Pinel-Alloul B, Plath K, Codd GA, Lampert W (2004) Effects of Microcystis aeruginosa and purified microcystin-LR on the feeding behavior of Daphnia pulicaria. Limnol Oceanogr 49:666–679

    Google Scholar 

  • Gutiérrez-Praena D, Pichardo S, Jos Á, Cameán AM (2011) Toxicity and glutathione implication in the effects observed by exposure of the liver fish cell line PLHC-1 to pure cylindrospermopsin. Ecotox Environ Safe 74:1567–1572

    Google Scholar 

  • Guzmán-Guillén R, Gutiérrez-Praena D, De los Ángeles Risalde M, Moyano R, Prieto AI, Pichardo S, Jos Á, Vasconcelos V, Cameán AM (2014) Immunohistochemical approach to study cylindrospermopsin distribution in tilapia (Oreochromis niloticus) under different exposure conditions. Toxins 6:283–303

    Google Scholar 

  • Hawkins PR, Runnegar MT, Jackson A, Falconer I (1985) Severe hepatotoxicity caused by the tropical cyanobacterium (blue-green alga) Cylindrospermopsis raciborskii (Woloszynska) Seenaya and Subba Raju isolated from a domestic water supply reservoir. Appl Environ Microbiol 50:1292–1295

    CAS  Google Scholar 

  • Hawkins PR, Chandrasena NR, Jones GJ, Humpage AR, Falconer IR (1997) Isolation and toxicity of Cylindrospermopsis raciborskii from an ornamental lake. Toxicon 35:341–346

    CAS  Google Scholar 

  • Heresztyn T, Nicholson BC (2001) Determination of cyanobacterial hepatotoxins directly in water using a protein phosphatase inhibition assay. Water Res 35:3049–3056

    CAS  Google Scholar 

  • Hilborn ED, Roberts VA, Backer L, Deconno E, Egan JS, Hyde JB, Nicholas DC, Wiegert EJ, Billing LM, Diorio M, Mohr MC, Hardy JF, Wade TJ, Yoder JS, Hlavsa MC, Centers for Disease Control and Prevention (2014) Algal bloom-associated disease outbreaks among users of freshwater lakes—United States, 2009–2010. MMWR Morb Mortal Wkly Rep 63(1):11–15

    Google Scholar 

  • Hooser SB, Kuhlenschmidt MS, Dahlem AM, Beasley VR, Carmichael WW, Haschek WM (1991) Uptake and subcellular localization of tritiated dihydro-microcystin-LR in rat liver. Toxicon 29:589–601

    CAS  Google Scholar 

  • Humpage AR, Fenech M, Thomas P, Falconer IR (2000) Micronucleus induction and chromosome loss in transformed human white cells indicate clastogenic and aneugenic action of the cyanobacterial toxin, cylindrospermopsin. Mutat Res 472:155–161

    CAS  Google Scholar 

  • Humpage AR, Fontaine F, Froscio S, Burcham P, Falconer IR (2005) Cylindrospermopsin genotoxicity and cytotoxicity: role of cytochrome P-450 and oxidative stress. J. Toxicol 68:739–753

    CAS  Google Scholar 

  • Hyenstrand P, Rohrlack T, Beattie KA, Metcalf JS, Codd GA, Christoffersen K (2003) Laboratory studies of dissolved radiolabelled microcystin-LR in lake water. Water Res 37:3299–3306

    CAS  Google Scholar 

  • Jungmann D, Benndorf J (1994) Toxicity to Daphnia of a compound extracted from laboratory and natural Microcystis spp., and the role of microcystins. Freshw Biol 32:13–20

    CAS  Google Scholar 

  • Kaloudis T, Zervou SK, Tsimeli K, Triantis TM, Fotiou T, Hiskia A (2013) Determination of microcystins and nodularin (cyanobacterial toxins) in water by LC–MS/MS. Monitoring of Lake Marathonas, a water reservoir of Athens, Greece. J Hazard Mater 263:105–115

    Google Scholar 

  • Khodarev NN, Park JO, Yu J, Gupta N, Nodzenski E, Roizman B, Weichselbaum RR (2001) Dose-dependent and independent temporal patterns of gene responses to ionizing radiation in normal and tumor cells and tumor xenografts. PNAS 98:12665–12670

    CAS  Google Scholar 

  • Kiviranta J, Sivonen K, Niemelä S, Huovinen K (1991) Detection of toxicity of cyanobacteria by Artemia salina bioassay. Environ Toxicol Water Qual 6:423–436

    CAS  Google Scholar 

  • Kleinteich J, Wood SA, Puddick J, Schleheck D, Küpper FC, Dietrich D (2013) Potent toxins in Arctic environments–presence of saxitoxins and an unusual microcystin variant in Arctic freshwater ecosystems. Chem Biol Interact 206:423–431

    CAS  Google Scholar 

  • Koreivienė J, Belous O (2012) Methods for cyanotoxins detection. Botanica 18:58–65

    Google Scholar 

  • Lahti K, Ahtiainen J, Rapala J, Sivonen K, Niemelä S (1995) Assessment of rapid bioassays for detecting cyanobacterial toxicity. Lett Appl Microbiol 21:109–114

    CAS  Google Scholar 

  • Lankoff A, Banasik A, Obe G, Deperas M, Kuzminski K, Tarczynska M, Jurczak T, Wojcik A (2003) Effect of microcystin-LR and cyanobacterial extract from polish reservoir of drinking water on cell cycle progression, mitotic spindle, and apoptosis in CHO-K1 cells. Toxicol Appl Pharmacol 189:204–213

    Google Scholar 

  • Lankoff A, Krzowski Ł, Głąb J, Banasik A, Lisowska H, Kuszewski T, Góźdź S, Wójcik A (2004) DNA damage and repair in human peripheral blood lymphocytes following treatment with microcystin-LR. Mutat Res 559:131–142

    Google Scholar 

  • Lankoff A, Banasik A, Duma A, Ochniak E, Lisowska H, Kuszewski T, Góźdź S, Wojcik A (2006a) A comet assay study reveals that aluminium induces DNA damage and inhibits the repair of radiation-induced lesions in human peripheral blood lymphocytes. Toxicol Lett 161:27–36

    Google Scholar 

  • Lankoff A, Bialczyk J, Dziga D, Carmichael W, Lisowska H, Wojcik A (2006b) Inhibition of nucleotide excision repair (NER) by microcystin-LR in CHO-K1 cells. Toxicon 48:957–965

    CAS  Google Scholar 

  • Lankoff A, Wojcik A, Fessard V, Meriluoto J (2006c) Nodularin-induced genotoxicity following oxidative DNA damage and aneuploidy in HepG2 cells. Toxicol Lett 164:239–248

    CAS  Google Scholar 

  • Lankoff A, Wojcik A, Lisowska H, Bialczyk J, Dziga D, Carmichael W (2007) No induction of structural chromosomal aberrations in cylindrospermopsin-treated CHO-K1 cells without and with metabolic activation. Toxicon 50:1105–1115

    CAS  Google Scholar 

  • Li J, Song L (2007) Applicability of the MTT assay for measuring viability of cyanobacteria and algae, specifically for Microcystis aeruginosa (Chroococcales, Cyanobacteria). Phycologia 46:593–599

    Google Scholar 

  • Li Y, Li J, Huang H, Yang M, Zhuang D, Cheng X, Zhang H, Fu X (2016) Microcystin-LR induces mitochondria-mediated apoptosis in human bronchial epithelial cells. Exp Ther Med 12:633–640

    Google Scholar 

  • Liu L, Jokela J, Wahlsten M, Nowruzi B, Permi P, Zhang YZ, Xhaard H, Fewer DP, Sivonen K (2014) Nostosins, trypsin inhibitors isolated from the terrestrial cyanobacterium Nostoc sp. strain FSN. J Nat Prod 77:1784–1790

    Google Scholar 

  • Llana-Ruiz-Cabello M, Pichardo S, Maisanaba S, Puerto M, Prieto AI, Gutierrez-Praena D, Jos A, Cameán AM (2015) In vitro toxicological evaluation of essential oils and their main compounds used in active food packaging: a review. Food Chem Toxicol 81:9–27

    Google Scholar 

  • Logan TJ (1997) Critical reviews in environmental science and technology. CRC Press

    Google Scholar 

  • Lukowski AL, Mallik L, Hinze ME, Carlson BM, Ellinwood DC, Pyser JB, Koutmos M, Narayan AR (2020) Substrate promiscuity of a paralytic shellfish toxin amidinotransferase. ACS Chem Biol 15:626–631

    Google Scholar 

  • Malik JK, Bharti VK, Rahal A, Kumar D, Gupta RC (2020) Cyanobacterial (blue-green algae) toxins. In: Handbook of toxicology of chemical warfare agents. Elsevier, pp 467–478

    Google Scholar 

  • Manage P (2019) Cyanotoxins: a hidden cause of chronic kidney disease of unknown etiology (CKDu) in Sri Lanka-a review. Sri Lanka J Aquat Sci 24. https://doi.org/10.4038/SLJAS.V24I1.7562

  • Manganelli M, Scardala S, Stefanelli M, Palazzo F, Funari E, Vichi S, Buratti FM, Testai E (2012) Emerging health issues of cyanobacterial blooms. Ann Ist Super Sanita 48:415–428

    Google Scholar 

  • Mankiewicz J, Walter Z, Tarczynska M, Palyvoda O, Wojtysiak-Staniaszczyk M, Zalewski M (2002) Genotoxicity of cyanobacterial extracts containing microcystins from polish water reservoirs as determined by SOS chromotest and comet assay. Environ Toxicol 17:341–350

    CAS  Google Scholar 

  • McGregor GB, Stewart I, Sendall BC, Sadler R, Reardon K, Carter S, Wruck D, Wickramasinghe W (2012) First report of a toxic Nodularia spumigena (Nostocales/Cyanobacteria) bloom in sub-tropical Australia. I. Phycological and public health investigations. Int J Environ Res Public Health 9:2396–2411

    Google Scholar 

  • Meili N, Christen V, Fent K (2016) Nodularin induces tumor necrosis factor-alpha and mitogen-activated protein kinases (MAPK) and leads to induction of endoplasmic reticulum stress. Toxicol Appl Pharmacol 300:25–33

    CAS  Google Scholar 

  • Metcalf J, Bell S, Codd G (2000) Production of novel polyclonal antibodies against the cyanobacterial toxin microcystin-LR and their application for the detection and quantification of microcystins and nodularin. Water Res 34:2761–2769

    CAS  Google Scholar 

  • Metcalf J, Lindsay J, Beattie K, Birmingham S, Saker M, Törökné A, Codd G (2002) Toxicity of cylindrospermopsin to the brine shrimp Artemia salina: comparisons with protein synthesis inhibitors and microcystins. Toxicon 40:1115–1120

    CAS  Google Scholar 

  • Minshull J, Straight A, Rudner AD, Dernburg AF, Belmont A, Murray AW (1996) Protein phosphatase 2A regulates MPF activity and sister chromatid cohesion in budding yeast. Curr Biol 6:1609–1620

    CAS  Google Scholar 

  • Mohamed ZA (2008) Toxic cyanobacteria and cyanotoxins in public hot springs in Saudi Arabia. Toxicon 51:17–27

    CAS  Google Scholar 

  • Mohamed ZA, Al Shehri AM (2007) Cyanobacteria and their toxins in treated-water storage reservoirs in Abha city, Saudi Arabia. Toxicon 50:75–84

    CAS  Google Scholar 

  • Mohamed ZA, Al Shehri AM (2009) Microcystin-producing blooms of Anabaenopsis arnoldi in a potable mountain lake in Saudi Arabia. FEMS Microbiol Ecol 69:98–105

    CAS  Google Scholar 

  • Mohamed ZA, Deyab MA, Abou-Dobara MI, El-Raghi WM (2016) Occurrence of toxic cyanobacteria and microcystin toxin in domestic water storage reservoirs. Egypt J Water Supply Res Technol Aqua 65:431–440

    Google Scholar 

  • Moreira C, Gomes C, Vasconcelos V, Antunes A (2020) Cyanotoxins occurrence in Portugal: a new report on their recent multiplication. Toxins 12:154

    CAS  Google Scholar 

  • Nesslany F, Marzin D (1999) A micromethod for the in vitro micronucleus assay. Mutagenesis 14:403–410

    CAS  Google Scholar 

  • Nicholson BC, Burch MD (2001) Evaluation of analytical methods for detection and quantification of cyanotoxins in relation to Australian drinking water guidelines. National Health and Medical Research Council of Australia Canberra

    Google Scholar 

  • Nong Q, Komatsu M, Izumo K, Indo HP, Xu B, Aoyama K, Majima HJ, Horiuchi M, Morimoto K, Takeuchi T (2007) Involvement of reactive oxygen species in Microcystin-LR-induced cytogenotoxicity. Free Radic Res 41:1326–1337

    Google Scholar 

  • Norris RLG, Seawright AA, Shaw GR, Smith MJ, Chiswell RK, Moore MR (2001) Distribution of 14C cylindrospermopsin in vivo in the mouse. Environ Toxicol 16(6):498–505

    Google Scholar 

  • Nowruzi B, Porzani SJ (2021) Toxic compounds produced by cyanobacteria belonging to several species of the order Nostocales: a review. J Appl Toxicol 41(4):510–548

    CAS  Google Scholar 

  • Nowruzi B, Khavari-Nejad R-A, Sivonen K, Kazemi B, Najafi F, Nejadsattari T (2012) Identification and toxigenic potential of a Nostoc sp. Algae 27:303

    CAS  Google Scholar 

  • Nowruzi B, Khavari-Nejad RA, Sivonen K, Kazemi B, Najafi F, Nejadsattari T (2013) Identification and toxigenic potential of a cyanobacterial strain (Stigomena sp.). PBS 3:79–85

    Google Scholar 

  • Nowruzi B, Blanco S, Nejadsattari T (2018a) Chemical and molecular evidences for the poisoning of a duck by anatoxin-a, nodularin and cryptophycin at the coast of Lake Shoormast (Mazandaran province, Iran). Int J Algae 20:359–376

    Google Scholar 

  • Nowruzi B, Haghighat S, Fahimi H, Mohammadi E (2018b) Nostoc cyanobacteria species: a new and rich source of novel bioactive compounds with pharmaceutical potential. JPHSR 9:5–12

    Google Scholar 

  • Nowruzi B, Wahlsten M, Jokela J (2019) A report on finding a new peptide aldehyde from cyanobacterium Nostoc sp. Bahar M by LC-MS and Marfey’s analysis. IJB 17:e1853

    Google Scholar 

  • Nowruzi B, Sarvari G, Blanco S (2020a) Applications of cyanobacteria in biomedicine. In: Handb. algal sci. microbiol. technol. med. Elsevier, Amsterdam

    Google Scholar 

  • Nowruzi B, Sarvari G, Blanco S (2020b) The cosmetic application of cyanobacterial secondary metabolites. Algal Res 49:101959

    Google Scholar 

  • Ohtani I, Moore RE, Runnegar MT (1992) Cylindrospermopsin: a potent hepatotoxin from the blue-green alga Cylindrospermopsis raciborskii. J Am Chem Soc 114:7941–7942

    CAS  Google Scholar 

  • Okumura DT, Sotero-Santos RB, Takenaka RA, Rocha O (2007) Evaluation of cyanobacteria toxicity in tropical reservoirs using crude extracts bioassay with cladocerans. Ecotoxicology 16:263–270

    CAS  Google Scholar 

  • Pace JG, Robinson NA, Miura GA, Matson CF, Geisbert TW, White JD (1991) Toxicity and kinetics of [3H] microcystin-LR in isolated perfused rat livers. Toxicol Appl Pharmacol 107(3):391–401

    Google Scholar 

  • Paerl HW, Fulton RS, Moisander PH, Dyble J (2001) Harmful freshwater algal blooms, with an emphasis on cyanobacteria. The Scientific World JOURNAL 1:76–113

    Google Scholar 

  • Palus J, Dziubaltowska E, Stanczyk M, Lewinska D, Mankiewicz-Boczek J, Izydorczyk K, Bonislawska A, Jurczak T, Zalewski M, Wasowicz W (2007) Biomonitoring of cyanobacterial blooms in polish water reservoir and the cytotoxicity and genotoxicity of selected cyanobacterial extracts. IJOMEH 20:48–65

    Google Scholar 

  • Park DL, Aguirre-Flores I, Scott WF, Alterman E (1986) Evaluation of chicken embryo, brine shrimp, and bacterial bioassays for saxitoxin. J Toxicol Environ Health Part A Curr Issues 18:589–594

    CAS  Google Scholar 

  • Parry EM, Parry JM, Corso C, Doherty A, Haddad F, Hermine TF, Johnson G, Kayani M, Quick E, Warr T, Williamson J (2002) Detection and characterization of mechanisms of action of aneugenic chemicals. Mutagenesis 17:509–521

    Google Scholar 

  • Pegram R, Humpage A, Neilan B, Runnegar M, Nichols T, Thacker R, Pflugmacher S, Etheridge S, Love A (2008) Cyanobacterial harmful algal blooms: chapter 15: cyanotoxins workgroup report. US Environ Prot Agency Pap 34

    Google Scholar 

  • Piyathilaka M, Pathmalal M, Tennekoon K, De Silva B, Samarakoon S, Chanthirika S (2015) Microcystin-LR-induced cytotoxicity and apoptosis in human embryonic kidney and human kidney adenocarcinoma cell lines. Microbiology 161:819–828

    CAS  Google Scholar 

  • Porzani SJ, Lorenzi AS, Eghtedari M, Nowruzi B (2021) Interactions of dehydrogenase enzymes with nanoparticles industrial and medical applications and challenges: mini-review. Mini Rev Med Chem 21(11):1351–1366

    CAS  Google Scholar 

  • Potterat O, Hamburger M (2006) Natural products in drug discovery-concepts and approaches for tracking bioactivity. Curr Org Chem 10:899–920

    CAS  Google Scholar 

  • Preece E, Moore BC, Hardy FJ (2015) Transfer of microcystin from freshwater lakes to Puget Sound, WA and toxin accumulation in marine mussels (Mytilus trossulus). Ecotox Environ Safe 122:98–105

    CAS  Google Scholar 

  • Prieto AI, Pichardo S, Jos Á, Moreno I, Cameán AM (2007) Time-dependent oxidative stress responses after acute exposure to toxic cyanobacterial cells containing microcystins in tilapia fish (Oreochromis niloticus) under laboratory conditions. Aquat Toxicol 84:337–345

    CAS  Google Scholar 

  • Puerto M, Pichardo S, Jos Á, Cameán AM (2009) Comparison of the toxicity induced by microcystin-RR and microcystin-YR in differentiated and undifferentiated Caco-2 cells. Toxicon 54:161–169

    CAS  Google Scholar 

  • Puerto M, Pichardo S, Jos Á, Cameán AM (2010) Microcystin-LR induces toxic effects in differentiated and undifferentiated Caco-2 cells. Arch Toxicol 84:405–410

    CAS  Google Scholar 

  • Rajabpour N, Nowruzi B, Ghobeh M (2019) Investigation of the toxicity, antioxidant and antimicrobial activities of some cyanobacterial strains isolated from different habitats. Acta Biol Slov 62:2

    Google Scholar 

  • Rao PL, Bhattacharya R, Parida M, Jana A, Bhaskar A (1998) Freshwater cyanobacterium Microcystis aeruginosa (UTEX 2385) induced DNA damage in vivo and in vitro. Environ Toxicol Pharmacol 5:1–6

    Google Scholar 

  • Robinson NA, Pace JG, Matson CF, Miura GA, Lawrence WB (1990) Tissue distribution, excretion, and hepatic biotransformation of microcystin-LR in mice. Army Medical Research Inst of Infectious Diseases, Fort Detrick, MD

    Google Scholar 

  • Rohrlack T, Christoffersen K, Dittmann E, Nogueira I, Vasconcelos V, Börner T (2005) Ingestion of microcystins by Daphnia: intestinal uptake and toxic effects. Limnol Oceanogr 50:440–448

    CAS  Google Scholar 

  • Rosefort C, Fauth E, Zankl H (2004) Micronuclei induced by aneugens and clastogens in mononucleate and binucleate cells using the cytokinesis block assay. Mutagenesis 19:277–284

    CAS  Google Scholar 

  • Rouhiainen L, Jokela J, Fewer DP, Urmann M, Sivonen K (2010) Two alternative starter modules for the non-ribosomal biosynthesis of specific anabaenopeptin variants in Anabaena (Cyanobacteria). Chem Biol 17:265–273

    CAS  Google Scholar 

  • Ryan JA, Hightower LE (1994) Evaluation of heavy-metal ion toxicity in fish cells using a combined stress protein and cytotoxicity assay. Environ Toxicol Chem 13:1231–1240

    CAS  Google Scholar 

  • Safavi M, Nowruzi B, Estalaki S, Shokri M (2019) Biological activity of methanol extract from Nostoc sp. N42 and Fischerella sp. S29 isolated from aquatic and terrestrial ecosystems. Int J Algae 21:373–391

    Google Scholar 

  • Sanseverino I, António DC, Loos R, Lettieri T (2017) Cyanotoxins: methods and approaches for their analysis and detection. JRC Publication

    Google Scholar 

  • Seawright AA, Nolan CC, Shaw GR, Chiswell RK, Norris RL, Moore MR, Smith MJ (1999) The oral toxicity for mice of the tropical cyanobacterium Cylindrospermopsis raciborskii (Woloszynska). Environ Toxicol 14:135–142

    CAS  Google Scholar 

  • Sedda T, Baralla E, Varoni MV, Pasciu V, Lorenzoni G, Demontis MP (2016) Determination of microcystin-LR in clams (Tapes decussatus) of two Sardinian coastal ponds (Italy). Mar Pollut Bull 108:317–320

    CAS  Google Scholar 

  • Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191

    CAS  Google Scholar 

  • Sivonen K, Kononen K, Carmichael W, Dahlem A, Rinehart K, Kiviranta J, Niemela S (1989) Occurrence of the hepatotoxic cyanobacterium Nodularia spumigena in the Baltic Sea and structure of the toxin. Appl Environ Microbiol 55:1990–1995

    CAS  Google Scholar 

  • Sontag E (2001) Protein phosphatase 2A: the Trojan Horse of cellular signaling. Cell Signal 13:7–16

    CAS  Google Scholar 

  • Spoof L, Vesterkvist P, Lindholm T, Meriluoto J (2003) Screening for cyanobacterial hepatotoxins, microcystins and nodularin in environmental water samples by reversed-phase liquid chromatography–electrospray ionisation mass spectrometry. J Chromatogr A 1020:105–119

    CAS  Google Scholar 

  • Takenaka RA (2007) Avaliação da toxicidade de Microcystis aeruginosa e de florações naturais de cianobactérias de reservatórios do rio Tietê, SP. Universidade de São Paulo

    Google Scholar 

  • Takser L, Benachour N, Husk B, Cabana H, Gris D (2016) Cyanotoxins at low doses induce apoptosis and inflammatory effects in murine brain cells: potential implications for neurodegenerative diseases. Toxicol Rep 3:180–189

    CAS  Google Scholar 

  • Tencalla F, Dietrich D (1997) Biochemical characterization of microcystin toxicity in rainbow trout (Oncorhynchus mykiss). Toxicon 35:583–595

    CAS  Google Scholar 

  • Teneva I, Mladenov R, Popov N, Dzhambazov B (2005) Cytotoxicity and apoptotic effects of microcystin-LR and anatoxin-a in mouse lymphocytes. Folia Biol (Praha) 51:62

    CAS  Google Scholar 

  • Teneva I, Stoyanov P, Mladenov R, Dzhambazov B (2013) In vitro and in vivo toxicity evaluation of the freshwater cyanobacterium Heteroleiblenia kuetzingii. Open Life Sci 8:1216–1229

    CAS  Google Scholar 

  • Terao K, Ohmori S, Igarashi K, Ohtani I, Watanabe MF, Harada KI, Ito E, Watanabe M (1994) Electron microscopic studies on experimental poisoning in mice induced by cylindrospermopsin isolated from blue-green alga Umezakia natans. Toxicon 32:833–843

    Google Scholar 

  • Tice RR, Agurell E, Anderson D, Burlinson B, Hartmann A, Kobayashi H, Miyamae Y, Rojas E, Ryu JC, Sasaki YF (2000) Single cell gel/comet assay: guidelines for in vitro and in vivo. Environ Mol Mutagen 35:206–221

    Google Scholar 

  • Tillmanns AR, Pick FR, Aranda-Rodriguez R (2007) Sampling and analysis of microcystins: implications for the development of standardized methods. Environ Toxicol 22:132–143

    CAS  Google Scholar 

  • Triantis T, Tsimeli K, Kaloudis T, Thanassoulias N, Lytras E, Hiskia A (2010) Development of an integrated laboratory system for the monitoring of cyanotoxins in surface and drinking waters. Toxicon 55(5):979–989

    Google Scholar 

  • Valério E, Chaves S, Tenreiro R (2010) Diversity and impact of prokaryotic toxins on aquatic environments: a review. Toxins 2:2359–2410

    Google Scholar 

  • Vermes I, Haanen C, Steffens-Nakken H, Reutellingsperger C (1995) A novel assay for apoptosis flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled annexin V. J Immunol Methods 184:39–51

    CAS  Google Scholar 

  • Welker M, Von Döhren H (2006) Cyanobacterial peptides—nature’s own combinatorial biosynthesis. FEMS Microbiol Rev 30:530–563

    CAS  Google Scholar 

  • Weller MG (2013) Immunoassays and biosensors for the detection of cyanobacterial toxins in water. Sensors 13:15085–15112

    Google Scholar 

  • Wharton RE, Cunningham BR, Schaefer AM, Guldberg SM, Hamelin EI, Johnson RC (2019) Measurement of microcystin and nodularin activity in human urine by immunocapture-protein phosphatase 2A assay. Toxins 11:729

    CAS  Google Scholar 

  • Wiegand C, Peuthert A, Pflugmacher S, Carmeli S (2002) Effects of microcin SF608 and microcystin-LR, two cyanobacterial compounds produced by Microcystis sp., on aquatic organisms. Environ Toxicol 17:400–406

    Google Scholar 

  • Woese CR (1987) Bacterial evolution. Microbiol Rev 51:221–271

    Google Scholar 

  • Xu LH, Lam PK, Chen JP, Xu JM, Wong BS, Zhang YY, Wu RS, Harada KI (2000) Use of protein phosphatase inhibition assay to detect microcystins in Donghu Lake and a fish pond in China. Chemosphere 41:53–58

    Google Scholar 

  • Yen G, Chen H, Peng H (2001) Evaluation of the cytotoxicity, mutagenicity and antimutagenicity of emerging edible plants. Food Chem Toxicol 39:1045–1053

    CAS  Google Scholar 

  • Yoshida T, Makita Y, Tsutsumi T, Nagata S, Tashiro F, Yoshida F, Sekuima M, Tamura SI, Harada T, Maita K, Ueno Y (1998) Immunohistochemical localization of microcystin-LR in the liver of mice: a study on the pathogenesis of microcystin-LR-induced hepatotoxicity. Toxicol Pathol 26:411–418

    Google Scholar 

  • Young FM, Micklem J, Humpage AR (2008) Effects of blue-green algal toxin cylindrospermopsin (CYN) on human granulosa cells in vitro. Reprod Toxicol 25:374–380

    CAS  Google Scholar 

  • Zanchett G, Oliveira-Filho EC (2013) Cyanobacteria and cyanotoxins: from impacts on aquatic ecosystems and human health to anticarcinogenic effects. Toxins 5:1896–1917

    Google Scholar 

  • Zeck A, Eikenberg A, Weller MG, Niessner R (2001) Highly sensitive immunoassay based on a monoclonal antibody specific for [4-arginine] microcystins. Anal Chim Acta 441:1–13

    CAS  Google Scholar 

  • Žegura B, Sedmak B, Filipič M (2003) Microcystin-LR induces oxidative DNA damage in human hepatoma cell line HepG2. Toxicon 41:41–48

    Google Scholar 

  • Žegura B, Lah TT, Filipič M (2004) The role of reactive oxygen species in microcystin-LR-induced DNA damage. Toxicology 200:59–68

    Google Scholar 

  • Žegura B, Lah TT, Filipič M (2006) Alteration of intracellular GSH levels and its role in microcystin-LR-induced DNA damage in human hepatoma HepG2 cells. Mutat Res 611:25–33

    Google Scholar 

  • Žegura B, Volčič M, Lah TT, Filipič M (2008) Different sensitivities of human colon 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

    Google Scholar 

  • Zegura B, Sever N, Koloŝa K, Filipic M (2009) The influence of microcystin-LR on HepG2 cell proliferation and micronuclei formation. In: Proceedings of tenth international conference on environmental mutagenesis: the renaissance of environmental mutagenesis. Firenze, Italy, pp 20–25

    Google Scholar 

  • Žegura B, Gajski G, Štraser A, Garaj-Vrhovac V, Filipič M (2011a) Microcystin-LR induced DNA damage in human peripheral blood lymphocytes. Mutat Res 726:116–122

    Google Scholar 

  • Žegura B, Štraser A, Filipič M (2011b) Genotoxicity and potential carcinogenicity of cyanobacterial toxins–a review. Mutat Res Rev Mutat Res 727:16–41

    Google Scholar 

  • Zerikly M, Challis GL (2009) Strategies for the discovery of new natural products by genome mining. Chembiochem 10:625–633

    CAS  Google Scholar 

  • Zhan L, Sakamoto H, Sakuraba M, Wu DS, Zhang LS, Suzuki T, Hayashi M, Honma M (2004) Genotoxicity of microcystin-LR in human lymphoblastoid TK6 cells. Mutat Res 557:1–6

    Google Scholar 

  • Zurawell RW, Chen H, Burke JM, Prepas EE (2005) Hepatotoxic cyanobacteria: a review of the biological importance of microcystins in freshwater environments. J Toxicol Environ Health Part B 8:1–37

    CAS  Google Scholar 

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Author Contributions

Samaneh J. Porzani: writing – the original draft, the main manuscript text and graphical abstract.

Stella T. Lima: writing – review and editing, visualization.

James S. Metcalf: writing – review and editing, visualization.

Bahareh Nowruzi: writing – review, editing, and proof-read; supervised the manuscript.

Conflict of Interest

The authors declare that they have no conflict of interest.

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No human participants were involved in this study.

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Authors and Affiliations

  1. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

    Samaneh J. Porzani & Bahareh Nowruzi

  2. Center for Nuclear Energy in Agriculture, University of Sao Paulo, Piracicaba, Brazil

    Stella T. Lima

  3. Brain Chemistry Labs, Jackson, WY, USA

    James S. Metcalf

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  1. Samaneh J. Porzani
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  1. University of Amsterdam, Amsterdam, The Netherlands

    Pim de Voogt

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Porzani, S.J., Lima, S.T., Metcalf, J.S., Nowruzi, B. (2021). In Vivo and In Vitro Toxicity Testing of Cyanobacterial Toxins: A Mini-Review. In: de Voogt, P. (eds) Reviews of Environmental Contamination and Toxicology Volume 258. Reviews of Environmental Contamination and Toxicology, vol 258. Springer, Cham. https://doi.org/10.1007/398_2021_74

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