Nodularins in poisoning.

Nodularins are an important class of hepatotoxic cyclic pentapeptides that are produced by the cyanobacteria Nodularia spumigena. These peptides have been found worldwide and have been implicated in the deaths of animals as well as a potent cyanotoxin in humans. To date, approximately 10 variants have been discovered, among which nodularin-R is the most abundant. Though the mechanisms of their potential hepatotoxicity and carcinogenicity are not well understood, the most frequently proposed mechanisms are described here. Most importantly, a comprehensive review of nodularins in poisoning is presented, including their bioaccumulation in water, cyanobacterial blooms and aquatic animals, the IC50, LC50 and LD50 values determined in laboratories, and wild, domestic and laboratory animal cases. However, the hazard of these toxins to humans has not been fully elucidated, predominantly due to the lack of exposure data. One of reasons underlying is that most current methods are ill suited for clinical monitoring. Thus, the available assays for the detection and quantification of nodularins are described with an emphasis on the problems encountered with each assay. Our ultimate aim is to demonstrate the urgency of better understanding the toxicity of nodularins, especially in humans, and thus effectively protecting ourselves from their poisoning.

Ecosystem consequences of cyanobacteria in the northern Baltic Sea.

Cyanobacteria of the Baltic Sea have multiple effects on organisms that influence the food chain dynamics on several trophic levels. Cyanobacteria contain several bioactive compounds, such as alkaloids, peptides, and lipopolysaccharides. A group of nonribosomally produced oligopeptides, namely microcystins and nodularin, are tumor promoters and cause oxidative stress in the affected cells. Zooplankton graze on cyanobacteria, and when ingested, the hepatotoxins (nodularin) decrease the egg production of, for example, copepods. However, the observed effects are very variable, because many crustaceans are tolerant to nodularin and because cyanobacteria may complement the diet of grazers in small amounts. Cyanobacterial toxins are transferred through the food web from one trophic level to another. The transfer rate is relatively low in the pelagic food web, but reduced feeding and growth rates of fish larvae have been observed. In the benthic food web, especially in blue mussels, nodularin concentrations are high, and benthic feeding juvenile flounders have been observed to disappear from bloom areas. In the littoral ecosystem, gammarids have shown increased mortality and weakening of reproductive success under cyanobacterial exposure. In contrast, mysid shrimps seem to be tolerant to cyanobacterial exposure. In fish larvae, detoxication of nodularin poses a metabolic cost that is reflected as decreased growth and condition, which may increase their susceptibility to predation. Cyanobacterial filaments and aggregates also interfere with both hydromechanical and visual feeding of planktivores. The feeding appendages of mysid shrimps may clog, and the filaments interfere with prey detection of pike larvae. On the other hand, a cyanobacterial bloom may provide a refuge for both zooplankton and small fish. As the decaying bloom also provides an ample source of organic carbon and nutrients for the organisms of the microbial loop, the zooplankton species capable of selective feeding may thrive in bloom conditions. Cyanobacteria also compete for nutrients with other primary producers and change the nitrogen (N): phosphorus (P) balance of their environment by their N-fixation. Further, the bioactive compounds of cyanobacteria directly influence other primary producers, favoring cyanobacteria, chlorophytes, dinoflagellates, and nanoflagellates and inhibiting cryptophytes. As the selective grazers also shift the grazing pressure on other species than cyanobacteria, changes in the structure and functioning of the Baltic Sea communities and ecosystems are likely to occur during the cyanobacterial bloom season.

Estimating the accumulation and transfer of Nodularia spumigena toxins by the blue mussel Mytilus edulis: an appraisal from culture and mesocosm experiments.

Accumulation of Nodularia spumigena toxins by Mytilus edulis was studied during laboratory and mesocosm experiments in order to investigate the possible pathways of nodularin in mussels and calculate toxin budgets. Mussels were exposed to 0.2-15.6 microg nodularin l(-1), fed for up to 5 days with Nodularia cells from culture, or blooming in different nutrient-treated seawater. Toxin concentration was monitored with LC-ESI-MS. During different exposures, the amount of nodularin detected in mussels increased linearly with increasing toxin concentration in food and attained 0.28-13.8 microg of nodularin g dw(-1) of the mussel whole body tissue after 12 h. The digestive gland was found to be the tissue with the highest toxin concentration. Nodularin concentration in faeces was not proportional to faeces production or to toxin concentration in food; however, it seemed to be mostly related to food quality as well as to food availability. The percentage of nodularin taken up by the mussels, relative to the amount contained in the offered food, varied from 10% to 20%, depending on food quality. During a 5-day toxin accumulation experiment, the acute reduction of the toxin in mussel tissues the second day and the following stabilization, showed that probably mussels maintain low toxin levels via efficient elimination and/or toxin metabolism. After a 72 h depuration period, mussels showed 75% reduction in their toxin content.

Trophic transfer of cyanobacterial toxins from zooplankton to planktivores: consequences for pike larvae and mysid shrimps.

The aim of this study was to evaluate the potentially harmful effects of zooplankton preexposed to cyanobacteria on two planktivorous animals: a fish larva (pike, Esox lucius) and a mysid shrimp (Neomysis integer). The planktivores were fed zooplankton from a natural community that had been preexposed to cell-free extract or to purified toxin (nodularin) of the cyanobacterium Nodularia spumigena, and the growth, feeding, and pellet production of the planktivores, as well as the toxin content of the pellets, were measured. In addition, radiolabeled nodularin ((3)H-dihydronodularin) was used in separate experiments to measure the vector transfer of nodularin from zooplankton to their predators. During 11-day exposures, dissolved nodularin was transferred to pike larvae and N. integer via zooplankton at very low rates of accumulation. Treatment with N. spumigena extract decreased the ingestion and feces production rates of pike larvae. With purified nodularin alone, no such effect could be observed. No effect on molting cycle length, fecal pellet production, C:N ratio, or growth of N. integer was detected. The results suggest that dissolved cyanobacterial toxins released during bloom decay can have a negative impact on feeding and, hence, on the growth of fish larvae via zooplankton, even without direct contact between cyanobacteria and the fish.