Cyanobacteria hepatotoxic

Freshwater cyanobacteria produce a variety of peptides and similar peptides were also reported from marine cyanobacteria. Hepatotoxic microcystins are the most extensively studied peptides because of environmental con-... 

Strongly hepatotoxic cyclic heptapeptides produced by some species of freshwater cyanobacteria (blue-green algae) (28). These microcystins represent a health risk to humans through drinking water, since they have been found to act as tumor promoters (29). Several chromatographic analytical procedures for microcystins have been... 

In vitro studies on isolated cells including hepatocytes, erythrocytes, fibroblasts, and alveolar cells continue to demonstrate the specificity of action that these toxins have for liver cells (83,86,93). This specificity has led Aune and Berg (94) to use isolated rat hepatocytes as a screen for detecting hepatotoxic waterblooms of cyanobacteria. 

In summary, it can be reported that toxic cyanobacteria can produce neurotoxic, hepatotoxic, and dermatotoxic compounds that are a direct threat to animal and human water supplies. This threat increases as water bodies become more eutrophic, thus supporting higher production of toxic and nontoxic cyanobacteria. Presence of these potent natural product toxins poses an increasing threat to the maintenance of quality water supplies for agriculture, municipal, and recreational use. 

Zurawell RW, Chen H, Burke JM, Prepas EE (2005) Hepatotoxic cyanobacteria a review of the biological importance of microcystins in freshwater environments. J Toxicol Env Heal B 8 1-37... 

These natural toxins are heptapeptides produced by cyanobacteria, which are associated with algal blooms. These substances are a hazard to wild and farm animals and sometimes humans who come in contact with contaminated water. There are a number of these toxins, some of which such as microcystin LR are hepatotoxic, causing damage to both hepatocytes and endothelial cells. The toxins have some unusual structural features, incorporating three D-amino acids and two very unusual ones, namely, methyldehydro alanine (Mdha) and amino-methoxy-trimethyl-phenyl-decadi-enoic acid (Adda) (Fig. 7.26). 

These natural toxins are heptapeptides produced by cyanobacteria and have unusual structural features, incorporating three D-amino acids. Microcystin LR is hepatotoxic, as a result of inactivation of protein phosphatases, which leads to breakdown of the cytoskeleton and cell death. 

W.P. Brooks and G.A. Codd, Immunoassay of hepatotoxic cultures and water blooms of cyanobacteria using Microcystis areuginosa peptide toxin polyclonal antibodies, Environ. Technol. Lett., 9 (1988) 1343-1348. 

Campbell, D.L., Lawton, L.A., Beattie, K.A. and Codd, G.A. (1994) Comparative assessment of the specificity of the brine shrimp and Microtox assays to hepatotoxic (microcystin-LR-containing) cyanobacteria, Environmental Toxicology and Water Quality 9 (1), 71-77. 

In the marine environment, cyanobacteria are emerging as contributors to HABs, especially in tropical environments however, their impact is likely more pronounced on the ecological structure of shallow-water reef systems than on human populations. But in some locations, such as the East Coast of Australia, extensive blooms of Lyngbya majuscula, which produce the hepatotoxic lyngbyatoxins, have influenced human health. Nevertheless, some populations of this same species from elsewhere in the world do produce neurotoxic natural products, as reviewed in the latter part of... 

One of the invariant amino acids is a unique P-amino acid called Adda (2S,3S,8S,9S)-3 amino-9 methoxy-2,6,8-trimethyl-10-phei5fldeca-4,6-dienoic acid is the most unusual structure in this group of cyanobacterial cyclic peptide toxins). A two-letter suffix (XY) is ascribed to each individual toxin to denote the two variant amino acids (Carmichael 1988). X is commonly leucine, arginine, or tyrosine. Y is arginine, alanine, or methionine. Variants of all the invarianf amino acids have now been reported, e.g., desmethyl amino acids and/or replacement of the 9-methoxy group of Adda by an acetyl moiety. Currently there are in excess of 60 variants of microcystin that have been characterized (Rinehart 1994 Sivonen and Jones 1999). Of these 60 compounds, microcystin-LR would appear to be the microcystin most commonly found in cyanobacteria. It is also common for more than one microcystin to be found in a particular strain of cyanobacterium (Namikoshi 1992 Lawton 1995). The microcystin variants may also differ in toxicity (Carmichael 1993). The literature indicates that hepatotoxic blooms ofM aeruginosa containing microcystins occur commonly worldwide. 

The microcystins are hepatotoxic produets of freshwater blooms of cyanobacteria of Microcystis, Anabena, and Oscillatoria species (Chen et al, 1993 Luu et al, 1993), with Microcystis aeruginosa being the most common. 

The most important of the peptidic phosphatase inhibitors are the microcystins and nodularin. Mycrocystins are heptapeptides characterised by the sequence cyclo(D-Ala-X-D-e/7t/i/ o-P-methylisoAsp-Y-Adda-D-isoGlu-iV-methyldehydroAla), where X and Y are different L-aminoacids, and Adda is the abbreviation of the P-aminoacid [25,35,85,95]-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4(E),6(E)-dienoic acid. In the most common microcystin, namely microcystin-LR, X is Leu and Y is Arg. This kind of compounds was considered to be the highly hepatotoxic principle of the cyanobacteria genera Microcystis, Artabaena and Oscillatoria. Apart Jfrom the variations represented by X and Y, other differences arising jfrom the demethylation of aminoacids, lead to the existence to more than fifty microcystins. The rare acid Adda is also... 

Freshwater cyanobacteria Microcystis, Oscillatoria, Ana-baena, and Nostoc produce several types of toxins, among which the most commonly detected are the hepatotoxic peptides microcystins. The general structure of the microcystins is cyclo-(D-Ala -X -D-MeAsp -Z -Adda -D-Glu -Mdha ), in which X and Z represent variable L-amino acids, D-MeAsp is D-eryf/iro-p-methylaspartic acid, Mdha is A-methyldehydroalanine, and Adda is the unusual C20 amino acid, (25,35,85,95)-3-amino-9-meth-oxy-2,6,8-trimethyl-10-phenyldeca-4( ),6( )-dienoic acid (Fig. 1). The structural differences in the microcystins mainly depend on the variability of the two L-amino acids (denoted X and Z), and secondarily on the methylation or demethylation of D-MeAsp and/or Mdha. More than 60 microcystins have been isolated from bloom samples and isolated strains of cyanobacteria. 

Among the few known examples of secondary metabolites synthesized by the phycobiont are the nostoclides (e.g., 90), " hepatotoxic microcystins (e.g., [ADMAdda ]microcystin-LR, 91), and the cytotoxic cryptophy-cins " from cyanobacteria. The cryptophycin analogue cryptophycin 52 (92) reached clinical trials for cancer chemotherapy but was later abandoned. " ... 

Cyanobacteria known to produce hepatotoxins include species of Microcystis (32-36), Anabaena (37-40), Nostoc (41,42), Oscillatoria (43,44) and the brackish water Nodularia spumigena (45,46). These cyanobacteria produce a wide range of toxins including neurotoxic alkaloids, lipopolysaccharides, phenolic compounds and most importantly, the cyclic hepatotoxic peptides microcystins and nodularins. Since both microcystins and nodularins were recently discovered even in shellfish (47) and tropical fish species (48), and a nodularin variant was isolated in Papua New Guinea also from the tropical marine sponge Theonella swinhoei (49), marine prokaryotes are apparently producing identical toxins as the cyanobacteria. However, since this nodularin variant was isolated from a marine sponge it may well be produced by a microbial symbiont. 

On closer examination, microcystins have been reported to cause hepatotoxic effects in fanned catfish (Zimba et al., 2001) and farmed sahnon (Andersen et al., 1993). Microcystins also produce pathological effects in tilapia (Preito et al., 2006), silver carp (Li et al., 2007), common carp (Fischer and Dietrich, 2000), and loach (Liu et al., 2002). The neurotoxin anatoxin-a, is produced by several genera of cyanobacteria and it has been reported to cause mortalities in juvenile common carp under experimental conditions (Oswald et al., 2006). Exposure to 0.768 pg/g dry weight of freeze-dried Anabaena spp. caused mortalities with 28 h. 

Throughout the world, it appears that hepatotoxic, microcystin-containing freshwater blooms of cyanobacteria are more commonly found than neurotoxic blooms (Table 40.1). Liver toxic blooms have been reported from aU continents where samples were collected for analysis. Nevertheless, mass occurrences of neurotoxic cyanobacteria are common in some countries and these have been reported from North America, Europe, and Australia, where they have caused... 

---