Toxicology and detection methods of the alkaloid neurotoxin produced by cyanobacteria, anatoxin-a.

Freshwater resources are under stress due to naturally occurring conditions and human impacts. One of the consequences is the proliferation of cyanobacteria, microphytoplankton organisms that are capable to produce toxins called cyanotoxins. Anatoxin-a is one of the main cyanotoxins. It is a very potent neurotoxin that was already responsible for some animal fatalities. In this review we endeavor to divulgate much of the internationally published information about toxicology, occurrence and detection methods of anatoxin-a. Cyanobacteria generalities, anatoxin-a occurrence and production as well as anatoxin-a toxicology and its methods of detection are the aspects focused in this review. Remediation of anatoxin-a occurrence will be addressed with a public health perspective. Final remarks call the attention for some important gaps in the knowledge about this neurotoxin and its implication to public health. Alterations of aquatic ecosystems caused by anatoxin-a is also addressed. Although anatoxin-a is not the more frequent cyanotoxin worldwide, it has to be regarded as a health risk that can be fatal to terrestrial and aquatic organisms because of its high toxicity.

[1]  D. Stevens,et al.  Analysis of Anatoxin-a by GCIECD , 1988 .

[2]  Elke Dittmann,et al.  Cyanobacterial toxins--occurrence, biosynthesis and impact on human affairs. , 2006, Molecular nutrition & food research.

[3]  K. James,et al.  Strategies to avoid the mis-identification of anatoxin-a using mass spectrometry in the forensic investigation of acute neurotoxic poisoning. , 2005, Journal of chromatography. A.

[4]  J. Tufariello,et al.  Synthesis of anatoxin-a: very fast death factor , 1984 .

[5]  I. Chorus,et al.  Anatoxin‐a and neurotoxic cyanobacteria in German lakes and reservoirs , 1999 .

[6]  D. Hilbelink,et al.  Evaluation of the subacute toxicity and teratogenicity of anatoxin-a. , 1980, Toxicon : official journal of the International Society on Toxinology.

[7]  K. Sivonen,et al.  Preliminary characterization of neurotoxic cyanobacteria blooms and strains from Finland , 1989 .

[8]  H. Mansell Synthetic approaches to anatoxin-a , 1996 .

[9]  J. J. Gilbert Susceptibility of planktonic rotifers to a toxic strain of Anabaena flos‐aquae , 1994 .

[10]  R. Draisci,et al.  Identification of anatoxins in blue-green algae food supplements using liquid chromatography-tandem mass spectrometry , 2001, Food additives and contaminants.

[11]  J. Ahtiainen,et al.  Assessment of rapid bioassays for detecting cyanobacterial toxicity , 1995, Letters in applied microbiology.

[12]  P. N. Viswanathan,et al.  Cyanobacterial toxins: a growing environmental concern. , 2003, Chemosphere.

[13]  E. Vuori,et al.  Facile detection of anatoxin-a in algal material by thin-layer chromatography with Fast Black K salt. , 1991, The Analyst.

[14]  K. Sivonen,et al.  Toxic cyanobacteria (blue-green algae) in Finnish fresh and coastal waters , 1990, Hydrobiologia.

[15]  K. Beattie,et al.  Liquid chromatography-electrospray ionization-mass spectrometry of cyanobacterial toxins , 1993 .

[16]  M. Takino,et al.  Analysis of anatoxin-a in freshwaters by automated on-line derivatization-liquid chromatography-electrospray mass spectrometry. , 1999, Journal of chromatography. A.

[17]  K. Sivonen,et al.  Anatoxin-a concentration inAnabaena andAphanizomenon under different environmental conditions and comparison of growth by toxic and non-toxicAnabaena-strains — a laboratory study , 1993, Journal of Applied Phycology.

[18]  Ho-Dong Park,et al.  Hepatotoxic microcystins and neurotoxic anatoxin‐a in cyanobacterial blooms from Korean lakes , 1998 .

[19]  D. Tanner,et al.  Total synthesis of pinnamine and anatoxin-a via a common intermediate. A caveat on the anatoxin-a endgame. , 2005, The Journal of organic chemistry.

[20]  G. Codd,et al.  Cyanobacterial toxins: risk management for health protection. , 2005, Toxicology and applied pharmacology.

[21]  S. Oishi,et al.  Isolation and identification of homoanatoxin-a from a toxic strain of the cyanobacterium Raphidiopsis mediterranea Skuja isolated from Lake Biwa, Japan , 2003 .

[22]  D. Barbini,et al.  Anatoxin-A and a previously unknown toxin in Anabaena planctonica from blooms found in Lake Mulargia (Italy). , 1994, Toxicon : official journal of the International Society on Toxinology.

[23]  A. Ledreux,et al.  First report in a river in France of the benthic cyanobacterium Phormidium favosum producing anatoxin-a associated with dog neurotoxicosis. , 2005, Toxicon : official journal of the International Society on Toxinology.

[24]  J. Gallon,et al.  Biosynthesis of the tropane-related cyanobacterial toxin anatoxin-a: role of ornithine decarboxylase. , 1990, Phytochemistry.

[25]  D. Bryant The Molecular Biology of Cyanobacteria , 1994, Advances in Photosynthesis.

[26]  G. Eaglesham,et al.  Analysis of cyanobacterial toxins by hydrophilic interaction liquid chromatography-mass spectrometry. , 2004, Journal of chromatography. A.

[27]  W. Budde,et al.  A LC/MS method for the determination of cyanobacteria toxins in water. , 2004, Analytical chemistry.

[28]  F. Benoit,et al.  Pressurized liquid extraction of toxins from cyanobacterial cells , 2005, Environmental toxicology.

[29]  G. Codd,et al.  Isolation and purification of peptide and alkaloid toxins from nabaena flos-aquae using high-performance thin-layer chromatography , 1988 .

[30]  J. Schripsema,et al.  1H NMR quantification in very dilute toxin solutions: application to anatoxin-a analysis. , 2005, Toxicon : official journal of the International Society on Toxinology.

[31]  K. Himberg Determination of anatoxin-a, the neurotoxin of Anabaena flos-aquae cyanobacterium, in algae and water by gas chromatography-mass spectrometry. , 1989, Journal of chromatography.

[32]  W. Carmichael,et al.  Liquid chromatography/mass spectrometric detection of anatoxin-a, a neurotoxin from cyanobacteria , 1993 .

[33]  A. P. Carvalho,et al.  Acute effects of an anatoxin-a producing cyanobacterium on juvenile fish-Cyprinus carpio L. , 2007, Toxicon : official journal of the International Society on Toxinology.

[34]  S. Martin,et al.  Application of intramolecular enyne metathesis to the synthesis of aza[4.2.1]bicyclics: enantiospecific total synthesis of (+)-anatoxin-a. , 2004, Organic letters.

[35]  J. M. Underwood,et al.  Tandem reactions of anions: A short and efficient route to ±anatoxin-a , 1996 .

[36]  O. Edwards,et al.  Synthesis of nor-anatoxin-a and anatoxin-a , 1977 .

[37]  L. Krienitz,et al.  Cyanobacteria and cyanobacterial toxins in the alkaline crater lakes Sonachi and Simbi, Kenya , 2005 .

[38]  Jussi Meriluoto,et al.  Toxic : cyanobacterial monitoring and cyanotoxin analysis , 2005 .

[39]  F. Fonnum,et al.  Enhancement of acetylcholine release by homoanatoxin-a from Oscillatoria formosa. , 1996, Environmental toxicology and pharmacology.

[40]  T. Cavalier-smith,et al.  Cell evolution and Earth history: stasis and revolution , 2006, Philosophical Transactions of the Royal Society B: Biological Sciences.

[41]  E. Albuquerque,et al.  Molecular mechanisms of the potent and stereospecific nicotinic receptor agonist (+)-anatoxin-a. , 1986, Molecular pharmacology.

[42]  B. Dräger Analysis of tropane and related alkaloids. , 2002, Journal of chromatography. A.

[43]  H. Rapoport,et al.  Synthetic and conformational studies on anatoxin-a: a potent acetylcholine agonist. , 1985, Journal of medicinal chemistry.

[44]  R. Rippka,et al.  Neurotoxins in axenic oscillatorian cyanobacteria: coexistence of anatoxin-a and homoanatoxin-a determined by ligand-binding assay and GC/MS. , 2005, Microbiology.

[45]  J. Callahan,et al.  Mass spectrometric analysis of anatoxin-a. , 1989, Journal of analytical toxicology.

[46]  D. Stevens,et al.  Stability studies on the cyanobacterial nicotinic alkaloid anatoxin-A. , 1991, Toxicon : official journal of the International Society on Toxinology.

[47]  I. Chorus,et al.  A highly sensitive analytical method for the neurotoxin anatoxin-a, using GC-ECD, and first application to laboratory cultures , 1996 .

[48]  J. Benndorf,et al.  Toxicity to Daphnia of a compound extracted from laboratory and natural Microcystis spp., and the role of microcystins , 1994 .

[49]  H. Rapoport,et al.  Synthesis of anatoxin a via intramolecular cyclization of iminium salts , 1979 .

[50]  C. Scrimgeour,et al.  Identification of anatoxin-A in benthic cyanobacteria (blue-green algae) and in associated dog poisonings at Loch Insh, Scotland. , 1992, Toxicon : official journal of the International Society on Toxinology.

[51]  K. James,et al.  Anatoxin-a elicits an increase in peroxidase and glutathione S-transferase activity in aquatic plants. , 2004, Aquatic toxicology.

[52]  R. Andersen,et al.  Effects of a homoanatoxin-a-containing extract from Oscillatoria formosa (Cyanophyceae/cyanobacteria) on neuromuscular transmission. , 1997, Toxicon : official journal of the International Society on Toxinology.

[53]  W. Carmichael,et al.  Muscle sensitivity differences in two avian species to anatoxin-a produced by the freshwater cyanophyte Anabaena flos-aquae NRC-44-1. , 1978, Canadian journal of zoology.

[54]  W. Carmichael,et al.  Toxicology and pharmacological action of anabaena flos-aquae toxin. , 1975, Science.

[55]  E. Viaggiu,et al.  Anatoxin‐a toxin in the cyanobacterium Planktothrix rubescens from a fishing pond in northern Italy , 2004, Environmental toxicology.

[56]  S. Oishi,et al.  Simultaneous production of homoanatoxin-a, anatoxin-a, and a new non-toxic 4-hydroxyhomoanatoxin-a by the cyanobacterium Raphidiopsis mediterranea Skuja. , 2003, Toxicon : official journal of the International Society on Toxinology.

[57]  J. M. Morin,et al.  Efficient total synthesis of (.+-.)-anatoxin a , 1985 .

[58]  J. Bartram,et al.  HUMAN HEALTH ASPECTS , 1999 .

[59]  J. Pawliszyn,et al.  Analysis of anatoxin-a in aqueous samples by solid-phase microextraction coupled to high-performance liquid chromatography with fluorescence detection and on-fiber derivatization. , 2002, Journal of chromatography. A.

[60]  J. Mclachlan,et al.  Isolation and culture of toxic strains of Anabaena flos-aquae (Lyngb.) de Bréb , 1964 .

[61]  W. Carmichael The toxins of cyanobacteria. , 1994, Scientific American.

[62]  Ø. Østensvik,et al.  SIMULTANEOUS DETERMINATION OF THE CYANOTOXINS ANATOXIN A, MICROCYSTIN DESMETHYL-3, LR, RR, AND YR IN FISH MUSCLE USING LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY , 2000 .

[63]  W. Schmidt,et al.  Simultaneous determination of cyanobacterial hepato-and neurotoxins in water samples by ion-pair supported enrichment and HPLC-ESI-MS-MS , 2001 .

[64]  O. Zinder,et al.  Catecholamine secretion from bovine adrenal chromaffin cells induced by the dextrorotatory isomer of anatoxin-a. , 1998, General pharmacology.

[65]  K. Sivonen,et al.  Toxicity of cyanobacteria to mosquito larvae―Screening of active compounds , 1993 .

[66]  K. Sivonen,et al.  Assessment of Environmental Conditions That Favor Hepatotoxic and Neurotoxic Anabaena spp. Strains Cultured under Light Limitation at Different Temperatures , 1998, Microbial Ecology.

[67]  E. Albuquerque,et al.  Behavioural effects of anatoxin, a potent nicotinic agonist, in rats , 1992, Neuropharmacology.

[68]  R. Smith,et al.  A rapid analysis of water for anatoxin a, the unstable toxic alkaloid from Anabaena flos-aquae, the stable non-toxic alkaloids left after bioreduction and a related amine which may be nature's precursor to anatoxin a. , 1987, Veterinary and human toxicology.

[69]  Claudia Wiegand,et al.  Cyanobacterial toxins in Lake Baringo, Kenya , 2003 .

[70]  J. Gallon,et al.  Biosynthesis of anatoxin-a by Anabaena flos-aquae: Examination of primary enzymic steps , 1994 .

[71]  K. James,et al.  The first identification of the rare cyanobacterial toxin, homoanatoxin-a, in Ireland. , 2003, Toxicon : official journal of the International Society on Toxinology.

[72]  R. Aronstam,et al.  Anatoxin-a interactions with cholinergic synaptic molecules. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[73]  A. Wilmotte Molecular Evolution and Taxonomy of the Cyanobacteria , 1994 .

[74]  Keith D. Hamill Toxicity in benthic freshwater cyanobacteria (blue‐green algae): First observations in New Zealand , 2001 .

[75]  E. S. Hunter,et al.  Potential developmental toxicity of anatoxin‐a, a cyanobacterial toxin , 2005, Journal of applied toxicology : JAT.

[76]  R. Mitchell,et al.  The toxicity of cyanobacterial toxins in the mouse: II Anatoxin-a , 1999, Human & experimental toxicology.

[77]  E. Albuquerque,et al.  Homoanatoxin: a potent analogue of anatoxin-A. , 1992, Biochemical pharmacology.

[78]  J. Waterbury,et al.  Generic assignments, strain histories, and properties of pure cultures of cyanobacteria , 1979 .

[79]  Wes R. Budakowski,et al.  Liquid chromatography-electrospray ionisation-mass spectrometry based method for the simultaneous determination of algal and cyanobacterial toxins in phytoplankton from marine waters and lakes followed by tentative structural elucidation of microcystins. , 2003, Journal of chromatography. A.

[80]  K. Sivonen,et al.  Detection of microcystins with protein phosphatase inhibition assay, high-performance liquid chromatography–UV detection and enzyme-linked immunosorbent assay , 2002 .

[81]  N. R. Hunter,et al.  Anatoxin-a, a toxic alkaloid from Anabaena flos-aquae NRC-44h , 1977 .

[82]  J. J. Gilbert,et al.  The effect of temperature on the response of Daphnia to toxic cyanobacteria , 1998 .

[83]  K. Sivonen,et al.  Biosynthesis of anatoxin-a in Anabaena flos-aquae and homoanatoxin-a in Oscillatoria formosa , 1995 .

[84]  H. Fromme,et al.  Occurrence of cyanobacterial toxins—microcystins and anatoxin‐a—in Berlin water bodies with implications to human health and regulations , 2000 .

[85]  F. Campos,et al.  In vivo Effects of the Anatoxin-a on Striatal Dopamine Release , 2006, Neurochemical Research.

[86]  V. Aggarwal,et al.  A Formal Asymmetric Synthesis of (+)-Anatoxin-a Using an Enantioselective Deprotonation Strategy on an Eight-Membered Ring. , 1999, Angewandte Chemie.

[87]  K. Jarema,et al.  Nicotine effects on the activity of mice exposed prenatally to the nicotinic agonist anatoxin-a. , 2005, Neurotoxicology and teratology.

[88]  V. Vasconcelos,et al.  Analysis of anatoxin-a in biological samples using liquid chromatography with fluorescence detection after solid phase extraction and solid phase microextraction. , 2007, Journal of chromatography. A.

[89]  K. James,et al.  Anatoxins and degradation products, determined using hybrid quadrupole time-of-flight and quadrupole ion-trap mass spectrometry: forensic investigations of cyanobacterial neurotoxin poisoning. , 2005, Rapid communications in mass spectrometry : RCM.

[90]  B. Trost,et al.  Asymmetric Synthesis of (−)-Anatoxin-a via an Asymmetric Cyclization Using a New Ligand for Pd-Catalyzed Alkylations , 1999 .

[91]  S. Pflugmacher,et al.  Ecotoxicological effects of selected cyanobacterial secondary metabolites: a short review. , 2005, Toxicology and applied pharmacology.

[92]  J. Bartram,et al.  LABORATORY ANALYSIS OF CYANOTOXINS , 1999 .

[93]  Kevin J James,et al.  Liquid chromatography with electrospray ion-trap mass spectrometry for the determination of anatoxins in cyanobacteria and drinking water. , 2003, Rapid communications in mass spectrometry : RCM.

[94]  K. James,et al.  Sensitive determination of anatoxin-a, homoanatoxin-a and their degradation products by liquid chromatography with fluorimetric detection. , 1998, Journal of chromatography. A.

[95]  S. Wonnacott,et al.  Anatoxin-a-evoked [3H]dopamine release from rat striatal synaptosomes , 1995, Neuropharmacology.

[96]  J. Priscu,et al.  Isolation and verification of anatoxin‐a producing clones of Anabaena flos‐aquae (Lyngb.) de Breb. from a eutrophic lake , 1993 .

[97]  Ian R. Falconer,et al.  Algal toxins in seafood and drinking water , 1993 .

[98]  J. Meriluoto,et al.  Screening for cyanobacterial hepatotoxins, microcystins and nodularin in environmental water samples by reversed-phase liquid chromatography-electrospray ionisation mass spectrometry. , 2003, Journal of chromatography. A.

[99]  W. Carmichael,et al.  Pharmacology of anatoxin-a, produced by the freshwater cyanophyte Anabaena flos-aquae NRC-44-1. , 1979, Toxicon : official journal of the International Society on Toxinology.

[100]  N. Gupta,et al.  Involvement of caspase and reactive oxygen species in cyanobacterial toxin anatoxin-a-induced cytotoxicity and apoptosis in rat thymocytes and Vero cells , 2002, Archives of Toxicology.

[101]  B. Neilan,et al.  Ecological and molecular investigations of cyanotoxin production. , 2001, FEMS microbiology ecology.

[102]  E. Albuquerque,et al.  Nicotinic acetylcholine receptors in cultured neurons from the hippocampus and brain stem of the rat characterized by single channel recording , 1987, FEBS letters.

[103]  See Hoi Wong,et al.  Detecting an algal toxin by high-pressure liquid chromatography , 1982 .

[104]  P. Brough,et al.  Determination of anatoxin-a and homoanatoxin in blue—green algal extracts by high-performance liquid chromatography and gas chromatography—mass spectrometry , 1993 .

[105]  L. Krienitz,et al.  Cyanobacteria and cyanobacterial toxins in three alkaline Rift Valley lakes of Kenya—Lakes Bogoria, Nakuru and Elmenteita , 2004 .

[106]  F. Barbosa,et al.  Cyanobacterial toxins detected by Thamnotoxkit (a double blind experiment) , 2000 .

[107]  J. J. Gilbert Effect of temperature on the response of planktonic rotifers to a toxic cyanobacterium , 1996 .

[108]  T. Gallagher,et al.  Synthetic and stereochemical studies directed towards anatoxin-a , 1991 .

[109]  K. James,et al.  Anatoxin-a in Irish freshwater and cyanobacteria, determined using a new fluorimetric liquid chromatographic method. , 1997, Toxicon : official journal of the International Society on Toxinology.

[110]  M. Amar,et al.  (+)‐Anatoxin‐a Is a Potent Agonist at Neuronal Nicotinic Acetylcholine Receptors , 1993, Journal of neurochemistry.

[111]  B. Lau,et al.  Improved method for the determination of anatoxin-a and two of its metabolites in blue-green algae using liquid chromatography with fluorescence detection. , 2005, Journal of AOAC International.

[112]  K. Sivonen,et al.  Biodegradability and adsorption on lake sediments of cyanobacterial hepatotoxins and anatoxin‐a , 1994, Letters in applied microbiology.

[113]  W. Carmichael,et al.  Human Fatalities from Cyanobacteria: Chemical and Biological Evidence for Cyanotoxins , 2001 .

[114]  E. Pinto,et al.  Determination of anatoxin-a in environmental water samples by solid-phase microextraction and gas chromatography-mass spectrometry. , 2006, Journal of separation science.

[115]  K. Sivonen,et al.  Production and biodegradation of cyanobacterial toxins - a laboratory study , 1991, Archiv für Hydrobiologie.

[116]  J. J. Gilbert,et al.  Effect of food availability on the response of planktonic rotifers to a toxic strain of the cyanobacterium Anabaena flos-aquae , 1996 .

[117]  I. Falconer Cyanobacterial toxins of drinking water supplies : cylindrospermopsins and microcystins , 2005 .

[118]  M. Pliński,et al.  Nodularia spumigena blooms and the occurrence of hepatotoxin in the Gulf of Gdańsk , 2003 .

[119]  S. Wonnacott,et al.  Anatoxin-a is a potent agonist of the nicotinic acetylcholine receptor of bovine adrenal chromaffin cells. , 1995, European journal of pharmacology.

[120]  S. S. H. Davarani,et al.  Analysis of anatoxin-a using polyaniline as a sorbent in solid-phase microextraction coupled to gas chromatography-mass spectrometry. , 2005, Journal of chromatography. A.

[121]  W. Carmichael,et al.  Two laboratory case studies on the oral toxicity to calves of the freshwater cyanophyte (blue-green alga) Anabaena flos-aquae NRC-44-1. , 1977, The Canadian veterinary journal = La revue veterinaire canadienne.

[122]  L. Krienitz,et al.  Contribution of hot spring cyanobacteria to the mysterious deaths of Lesser Flamingos at Lake Bogoria, Kenya. , 2003, FEMS microbiology ecology.

[123]  W. Carmichael,et al.  Detection of an anatoxin-a(s)-like anticholinesterase in natural blooms and cultures of cyanobacteria/blue-green algae from Danish lakes and in the stomach contents of poisoned birds. , 1997, Toxicon : official journal of the International Society on Toxinology.

[124]  W. Carmichael,et al.  Anatoxins from clones of Anabaena flos-aquae isolated from lakes of western Canada: With 3 figures and 2 tables in the text , 1978 .

[125]  M. Watanabe,et al.  Hepatotoxin (microcystin) and neurotoxin (anatoxin-a) contained in natural blooms and strains of cyanobacteria from Japanese freshwaters. , 1993, Natural toxins.

[126]  Katharina Jung,et al.  Effects of cyanobacterial toxins and cyanobacterial cell‐free crude extract on germination of alfalfa (Medicago sativa) and induction of oxidative stress , 2006, Environmental toxicology and chemistry.

[127]  W. Carmichael,et al.  A new procedure for the analysis and purification of naturally occurring anatoxin-a from the blue-green alga Anabaena flos-aquae. , 1989, Toxicon : official journal of the International Society on Toxinology.

[128]  E. Albuquerque,et al.  Anatoxin-a: a novel, potent agonist at the nicotinic receptor. , 1980, Molecular pharmacology.

[129]  M. Hunter,et al.  Green algal extracellular products regulate antialgal toxin production in a cyanobacterium. , 2000, Environmental microbiology.

[130]  M. Teixeira,et al.  Neurotoxic and hepatotoxic cyanotoxins removal by nanofiltration. , 2006, Water research.

[131]  Richard E. Moore,et al.  Investigations of a neurotoxic oscillatorialean strain (Cyanophyceae) and its toxin. Isolation and characterization of homoanatoxin‐a , 1992 .

[132]  J. Petersen,et al.  Chirospecific syntheses of (+)- and (-)-anatoxin a , 1984 .

[133]  R. Curini,et al.  Simple and rapid determination of anatoxin-a in lake water and fish muscle tissue by liquid-chromatography-tandem mass spectrometry. , 2006, Journal of chromatography. A.