Cyanotoxins: Effect on human, other vertebrates, aquatic community and plants

1.0 Introduction

Figure 01: Bloom condition in water ( Photo by Jonathan Larson on Unsplash)

1.1 What are cyanotoxins?

Cyanotoxins are a diverse group of secondary metabolites produced by various genera of cyanobacteria. Cyanobacteria are a group of photosynthetic bacteria which are mostly found in freshwater systems throughout the world. Due to their long evolutionary story, they have adapted to various climatic, geochemical and anthropogenic changes. Also, they can a colonize in marine or brackish water and are capable to survive extremely low and high temperatures. They have a key role in maintaining the environmental balance as well as the biodiversity of microorganisms and higher organism communities. They use sunlight as their energy source to perform photosynthesis and are specialized in converting the inert atmospheric nitrogen into inorganic forms such as nitrate or ammonium. For the growth of aquatic plants and algae they need all these forms of nitrogen.

Cyanotoxins are produced by bloom-forming cyanobacteria. Their rapid proliferation is regulated by a combination of environmental and anthropogenic factors. These cyanotoxins are highly toxic to many organisms including animals, plants, algae and humans. 

A bloom is a natural phenomenon caused by a significant production of biomass and is often characterized by the formation of a dense layer of cells at the surface of the water. The massive growth of cyanobacteria can be induced by different physical, chemical and biological factors such as warmer water temperature, the light intensity and the trophic status of the water (increased input of nutrients in aquatic systems, mainly phosphorous and nitrogen). 

Due to these circumstances, both planktonic and benthic cyanobacteria can reach high concentrations and have severe impacts on the ecosystem.  So that the bloom formation process is a critical environmental problem affecting on worldwide aquatic ecosystems including freshwater and brackish water. 

1.2  Classification of Cyanotoxins 

Based on the toxicological target cyanotoxins can be divided into four major categories.

Figure 02: Classification of cyanotoxins based on the biological target

1)     Hepatotoxins- act on liver (Microcystins and Nodularin)

2)     Cytotoxins-produce both hepatotoxic and neurotoxic effects (Cylindrospermopsin)

3)     Neurotoxins - cause injury on the nervous system (Anatoxins, Saxitoxins)

4)     Dermatoxins- cause irritant responses on contact (Lipopolysaccharide, Lyngbyatoxins) 

2.0 Cyanotoxin effect on human health

2.1 Hepatotoxins

EX: Microcystins and Nodularins

Microcystins (MCs) and Nodularins (NODs) are cyclic heptapeptides and pentapeptides with similar structures and mechanisms of action. An unusual β-amino acid in these structures is the reason for the toxicity. Microcystins are the most widespread and well-studied cyanotoxins. Among the MCs, Microcystin-LR (MC-LR) is the most studied one. Considering its high toxicity, the World Health Organization (WHO) has set a provisional guidance value, equal to 1μg/L, for the maximal acceptable concentration of MC-LR in drinking water. 

Both MCs and NODs synthesis is depending on the environmental factors like nutrients concentration and light intensity. With regard to the mechanism of action, MC-LR and NODs are inhibitors of serine/threonine-specific Protein Phosphatases 1 and 2A. The inhibition results in the disruption of the cytoskeleton and the subsequent cytolysis and apoptosis involving mainly the hepatocytes. NODs have a smaller ring-structure relative to the larger ring- structure of MC-LR which enables it to easily enter the hepatocytes and cause significant effects on the liver. It has been reported that MCs and NODs can also induce the formation of Reactive Oxygen Species which are involved in the induction of serious cellular damages such as genotoxicity and apoptosis. Some studies suggest that MCs and NODs might act as tumor promoters.  

2.2 Cytotoxins

EX: Cylindrospermopsin

Cylindrospermopsin (CYN) is classified as cytotoxin because it can affect both the liver (hepatotoxic) and the nervous system (neurotoxic). Once in the organism, the prime target of CYN is the liver, but other organs including the kidney, spleen and lungs might be affected. Cylindrospermopsin has a late and acute toxicity. Cell death is occurred due to the inhibition of protein synthesis. Exposure may leads to micronucleus induction, tumor initiation, fetal toxicity, Desoxyribonucleic Acid (DNA) strand breaks and chromosome loss. In addition, CYN can induce stress responses in human cell lines, presumably due to the damage to cellular components.

2.3 Neurotoxins

EX: Anatoxin-a, Anatoxin-a(s), Saxitoxins and β-Nmethylamino-L-alanine

Anatoxin-a (ATX-a) is a bicyclic alkaloid which is a potent neuromuscular blocking agent. ATX-a, acts by binding the acetylcholine receptors at the same position as acetylcholine and affects muscle junctions causing uncoordinated muscle contractions, respiratory dysfunctions and paralysis. After ingestion, the toxin is rapidly absorbed from the gastrointestinal tract, distributed to various body tissues including the brain and subsequently degraded.

Saxitoxins (STXs) are neurotoxins. They have been identified and characterized in both freshwater cyanobacteria and marine dinoflagellates. STXs binds to the voltage sodium channel in neuronal cells by blocking the nervous transmission.  It causes nerve dysfunction with death occurring from paralysis of respiratory muscles. It can also inhibit calciumand potassium channels in excitable cells thereby affecting the production of action potentials.It can cause fatal cardiac arrhythmias. Saxitoxins comprise a diverse group of toxins and are known as paralytic shellfish toxins, or PST, because their effects were first described in humans poisoned after eating contaminated shellfish. 

2.3  Dermatoxins

EX: Lypopolysaccharide (LPS), Lyngbyatoxin, Aplysiatoxin

Benthic cyanobacterium Lyngbya majuscula can secrete Lyngbyatoxins which causes acutecontact dermatitis. This cyanotoxin is slightly lipophilic and it can penetrate the human skin. During bathing activity, the body’s exposure to the water contaminated with Lyngbya majuscula might cause serious concerns. Aplysiatoxin, as with Lyngbyatoxins (LT), is the causative agent of severe contact dermatitis and is a potent tumor promoter which exerts its effects through the activation of Protein Kinase C.

Exposure to LPS endotoxins can make gastrointestinal diseases, allergic reactions, and cutaneous or ocular irritation. Initially, the monocytes and macrophages are stimulated, and next the neutrophils and platelets join in microcapillaries, causing vascular damage. Inflammatory cells release a variety of endogenous mediators, including arachidonic acid metabolites, platelet activation factor, cytokines, nitric oxide, toxic O metabolites, vasoactive amines, proteases and products of the complement and coagulation cascades.

✽ The table 2 shows the summarized details about the different cyanotoxins and their effect on human health. Source- (Isabella et al., 2016)

The figure 03 shows the affected organs by the cyanotoxins in human body.

Figure 03: Organs affected by cyanotoxins (Kubickova et al,2019 )

3.0 Cyanotoxin effect on aquatic community

Wide range of aquatic organisms is directly exposed to microcystins contained in their food (Phyto planktivorous fish, zooplankton etc.) and to microcystins dissolved in water, which may cause diverse effects. Aquatic microorganisms including algae, diatoms, Daphniids are also affected negatively some bacteria and fungi. It ultimately effects on the primary production of whole ecosystem. Cyanotoxins effects on the abundance of zooplanktons and phytoplankton including their body size and reproduction. They are deleterious on rotifers and cladocerans.

Many studies have done to study the of effect of cyanotoxins over a wide range of aquatic organisms, including invertebrates and vertebrates. It has reported acute effects such as reduction in survivorship, feeding inhibition, paralysis. As the chronic effects the reduction in growth and fecundity, biochemical alterations and behavioral alterations have been observed. Research has also focused on the potential for bioaccumulation and transferring of these toxins through the food chain.

Zooplanktons, gastropods, bivalves, crustaceans accumulate these cyanotoxins through their food and bioaccumulation and biomagnification is occurred through the aquatic food chains. This can affect on the higher trophic levels. The early developing stages including larval stages are killed due to these toxins. Not only aquatic arthropods, but the larvae of other insects can be killed. 

Fresh water mussels and freshwater crayfish are susceptible for these accumulations. Fish are susceptible group for the cyanotoxins. The cyanotoxins can affect on all stages of their lives. It can affect on their embryo, reproduction rate, survival, behaviors, mortality, mortality rate, time to hatching, hatching rate, skeletal malformations rate, and larval standard lengths and their overall growth and development.

The table 2 shows the Toxicity of microcystins for some species of fish (Source- Drobac, D et al, 2013)

        4.0  Cyanotoxin effect on other vertebrates                           

The majority of cyanotoxin-related research are focused on mammalian toxicity. However, Microcystin-producing blooms have been frequently involved in many incidents of fatal animal poisonings, including cattle, sheep, chickens, pigs, horse s, dogs, poultry and wild birds, fish or even rhinoceroses. Toxic microcystis can cause prostration, loss of equilibrium, muscle trembling, diarrhea and finally death of terrestrial vertebrates.

The occurrence of high mortality of birds is associated with the occurrence of cyanobacteria blooms. Microcystins can be lethal to chickens. All the higher vertebrates including top predators indirectly affected by cyanotoxins through the bioaccumulation via food chains.

5.0 Effect of Cyanotoxins on Plants

Different cyanotoxins have different phytotoxic levels including both aquatic and terrestrial plants.

·  ✽ MC-LR reduces the seed germination rate of aquatic plants by affecting on the metabolic activities of seeds during the germination process.

·   ✽ Seedling growth is reduced and the root development is inhibited.

·  ✽ Plant cell damage occurs as a result of cyanobacterial toxins. Necrotic lesions on leaves are also observed and likely due to Microcystin-induced stress.

·   ✽ Plant exposure to Microcystin results in the generation of reactive oxygen species such as hydrogen peroxide, and if the plant’s antioxidant capacity is plagued then the cells die. 

·   ✽ Under water plant Ceratophyllum demersum also presented reduced growth in the presence of MC-LR. 

   ✽Bioaccumulation of cyanotoxins in aquatic macrophytes can affect on the aquatic food webs with biomagnification along the food chains.

·  ✽ Cyanobacterial toxin uptake by crop plants occurs when irrigation is done with cyanobacteria containing water. Cyanobacterial toxins are phytotoxic. This means that they are toxic to and can induce negative responses in plants. When these are accumulated in crop plants it poses serious human health risk when they enter the food chain. Seedling growth is reduced and the root development is inhibited.

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6.0  References

·      1. Bláha, L., Babica, P. and Maršálek, B., 2009. Toxins produced in cyanobacterial water blooms-toxicity and risks. Interdisciplinary toxicology, 2(2), pp.36-41.

·    2. Bownik, A., 2010. Harmful algae: effects of alkaloid cyanotoxins on animal and human health. Toxin Reviews, 29(3-4), pp.99-114.

·   3. Chia, M.A., Kramer, B.J., Jankowiak, J.G., Bittencourt-Oliveira, M.D.C. and Gobler, C.J., 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(1), p.43.

·   4. Chorus, I. ed., 2012. Cyanotoxins: occurrence, causes, consequences. Springer Science & Business Media.

·    5.  Drobac, D., Tokodi, N., Simeunović, J., Baltić, V., Stanić, D. and Svirčev, Z., 2013. Human exposure to cyanotoxins and their effects on health. Arhiv za higijenu rada i toksikologiju, 64(2), pp.305-315.

·    6. Ferrão-Filho, A.D.S. and Kozlowsky-Suzuki, B., 2011. Cyanotoxins: bioaccumulation and effects on aquatic animals. Marine drugs, 9(12), pp.2729-2772.

·   7. Isabella, S., Sofia, C., Luca, P., Srdan, D. and Teresa, L., 2016. Algal bloom and its economic impact. Publications Office of the European Union,

·    8. Kubickova, B., Babica, P., Hilscherová, K. and Šindlerová, L., 2019. Effects of cyanobacterial toxins on the human gastrointestinal tract and the mucosal innate immune system. Environmental Sciences Europe, 31(1), p.31.

·    9.  Pflugmacher, S., 2002. Possible allelopathic effects of cyanotoxins, with reference to microcystin‐LR, in aquatic ecosystems. Environmental Toxicology: An International Journal, 17(4), pp.407-413.

·    10. Purkayastha, J., Gogoi, H.K. and Singh, L., 2010. Plant-Cyanobacteria interaction: Phytotoxicity of cyanotoxins. Journal of Phytology.

·   11. Sanseverino, I., Conduto António, D., Loos, R. and Lettieri, T., 2017. Cyanotoxins: methods and approaches for their analysis and detection. Joint Research Centre (JRC), the European Commission’s science and knowledge service.