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Palytoxins are a group of highly potent and structurally complex marine toxins that rank among some of the most toxic substances known to science. Palytoxins are naturally synthesized by a variety of marine organisms, including Palythoa zoanthids, Ostreopsis dinoflagellates, and Trichodesmium cyanobacteria, and are widely distributed in tropical and temperate regions where they can bioaccumulate in marine life. The evolution of research on palytoxins has been an intricate exchange between interdisciplinary fields, drawing insights from chemistry, biology, medicine, and environmental science in efforts to better understand and mitigate the health risks associated with this family of toxins. In this review, we begin with a brief history covering the discovery of this group of toxins and the events that led to its isolation. We then focus on the chemical structure of these compounds and their proposed mechanism of action. Finally, we review in vitro, ex vivo, and in vivo studies related to their toxicity, with the aim to provide a broad overview of the current knowledge on palytoxin toxinology. [ABSTRACT FROM AUTHOR]

Palytoxins are a group of highly potent and structurally complex marine toxins that rank among some of the most toxic substances known to science. Palytoxins are naturally synthesized by a variety of marine organisms, including Palythoa zoanthids, Ostreopsis dinoflagellates, and Trichodesmium cyanobacteria, and are widely distributed in tropical and temperate regions where they can bioaccumulate in marine life. The evolution of research on palytoxins has been an intricate exchange between interdisciplinary fields, drawing insights from chemistry, biology, medicine, and environmental science in efforts to better understand and mitigate the health risks associated with this family of toxins. In this review, we begin with a brief history covering the discovery of this group of toxins and the events that led to its isolation. We then focus on the chemical structure of these compounds and their proposed mechanism of action. Finally, we review in vitro, ex vivo, and in vivo studies related to their toxicity, with the aim to provide a broad overview of the current knowledge on palytoxin toxinology.

Palytoxins (PLTXs) are a group of complex and poisonous marine natural products that are toxic to marine life and even human beings. In the present study, the oxidative stress and immune response in the hepatopancreas and gills of Litopenaeus vannamei were assessed for 72 h after injection with PLTX extracts. Chemical and physiological parameters, e.g., the respiratory burst (O 2 −), activities of antioxidant enzymes, oxidative damage to lipids, carbonylation of proteins, and immune gene mRNA expression levels, were analysed. The results showed that the PLTX extract was not fatal to the shrimp but could reduce their mobility. The O 2 − levels in the gills gradually increased after exposure to PLTX extracts and were significantly higher than those in the control from 6 to 72 h. The malondialdehyde content, lipid peroxidation, protein carbonyl levels, and total antioxidant capacity in the gills all peaked at 12 h. At the same time, the gills were loosely connected, there was a clear disintegration of the epithelial tissue, and the stratum corneum disappeared after 12 h. In addition, compared to those in the control group, the PLTX extract treatment increased the O 2 − content, malondialdehyde content, lipid peroxidation, and protein carbonyl levels from 12 to 72 h, 24–48 h, 12–24 h, and 12–72 h after injection in the hepatopancreas of the shrimp, respectively. Both the Crustin and Toll gene expression levels significantly increased in the hepatopancreas compared to those in the control 6–72 h after injection of the toxin. In parallel, the expression levels of the manganese superoxide dismutase gene gradually decreased from 6 to 48 h and returned to normal levels after 72 h. Interestingly, the total antioxidant capacity also significantly increased compared to that in the control from 6 to 72 h. Our results indicate that although PLTX extracts cause lipid peroxidation and carbonylation of proteins in hepatopancreatic cells, leading to their damage, they did not cause a decrease in the total antioxidant capacity of the hepatopancreas. • Palytoxin is a complex poisonous molecule found in the marine environment. • Palytoxin was injected into the Pacific white shrimp Litopenaeus vannamei. • Palytoxin was not lethal but caused shrimp immobility. • Palytoxin increased markers of oxidative damage in the hepatopancreas. • Palytoxin did not cause a decrease in the total antioxidant capacity of the hepatopancreas. [ABSTRACT FROM AUTHOR]

Phycotoxins, which are produced by harmful microalgae and bioaccumulate in the marine food web, are of growing concern for Australia. These harmful algae pose a threat to ecosystem and human health, as well as constraining the progress of aquaculture, one of the fastest growing food sectors in the world. With better monitoring, advanced analytical skills and an increase in microalgal expertise, many phycotoxins have been identified in Australian coastal waters in recent years. The most concerning of these toxins are ciguatoxin, paralytic shellfish toxins, okadaic acid and domoic acid, with palytoxin and karlotoxin increasing in significance. The potential for tetrodotoxin, maitotoxin and palytoxin to contaminate seafood is also of concern, warranting future investigation. The largest and most significant toxic bloom in Tasmania in 2012 resulted in an estimated total economic loss of ~AUD$23M, indicating that there is an imperative to improve toxin and organism detection methods, clarify the toxin profiles of species of phytoplankton and carry out both intra- and inter-species toxicity comparisons. Future work also includes the application of rapid, real-time molecular assays for the detection of harmful species and toxin genes. This information, in conjunction with a better understanding of the life histories and ecology of harmful bloom species, may lead to more appropriate management of environmental, health and economic resources. [ABSTRACT FROM AUTHOR]

The new benthic toxic dinoflagellate, Ostreopsis fattorussoi sp. nov., is described from the Eastern Mediterranean Sea, Lebanon and Cyprus coasts, and is supported by morphological and molecular data. The plate formula, Po, 3′, 7″, 6c, 7s, 5‴, 2′′′′, is typical for the Ostreopsis genus. It differs from all other Ostreopsis species in that (i) the curved suture between plates 1′ and 3′ makes them approximately hexagonal, (ii) the 1′ plate lies in the left half of the epitheca and is obliquely orientated leading to a characteristic shape of plate 6″. The round thecal pores are bigger than the other two Mediterranean species ( O. cf. ovata and O. cf. siamensis). O. fattorussoi is among the smallest species of the genus ( DV: 60.07 ± 5.63 μm, AP: 25.66 ± 2.97 μm, W: 39.81 ± 5.05 μm) along with O. ovata. Phylogenetic analyses based on the LSU and internal transcribed spacer rDNA shows that O. fattorussoi belongs to the Atlantic/Mediterranean Ostreopsis spp. clade separated from the other Ostreopsis species. Ostreopsis fattorussoi produces OVTX-a and structural isomers OVTX-d and -e, O. cf. ovata is the only other species of this genus known to produce these toxins. The Lebanese O. fattorussoi did not produce the new palytoxin-like compounds (ovatoxin-i, ovatoxin-j1, ovatoxin-j2, and ovatoxin-k) that were previously found in O. fattorussoi from Cyprus. The toxin content was in the range of 0.28-0.94 pg · cell−1. On the Lebanon coast, O. fattorussoi was recorded throughout the year 2015 (temperature range 18°C-31.5°C), with peaks in June and August. [ABSTRACT FROM AUTHOR]

Palytoxin (PLTX), one the most potent marine toxins, and/or its analogs, have been identified in different marine organisms, such as Palythoa soft corals, Ostreopsis dinoflagellates, and Trichodesmium cyanobacteria. Although the main concern for human health is PLTXs entrance in the human food chain, there is growing evidence of adverse effects associated with inhalational, cutaneous, and/or ocular exposure to aquarium soft corals contaminated by PLTXs or aquaria waters. Indeed, the number of case reports describing human poisonings after handling these cnidarians is continuously increasing. In general, the signs and symptoms involvemainly the respiratory (rhinorrhea and coughing), skeletomuscular (myalgia, weakness, spasms), cardiovascular (electrocardiogram alterations), gastrointestinal (nausea), and nervous (paresthesia, ataxia, tremors) systems or apparates. The widespread phenomenon, the entity of the signs and symptoms of poisoning and the lack of control in the trade of corals as aquaria decorative elements led to consider these poisonings an emerging sanitary problem. This review summarizes literature data on human poisonings due to, or ascribed to, PLTX-containing soft corals, focusing on the different PLTX congeners identified in these organisms and their toxic potential. [ABSTRACT FROM AUTHOR]

Phycotoxins, which are produced by harmful microalgae and bioaccumulate in the marine food web, are of growing concern for Australia. These harmful algae pose a threat to ecosystem and human health, as well as constraining the progress of aquaculture, one of the fastest growing food sectors in the world. With better monitoring, advanced analytical skills and an increase in microalgal expertise, many phycotoxins have been identified in Australian coastal waters in recent years. The most concerning of these toxins are ciguatoxin, paralytic shellfish toxins, okadaic acid and domoic acid, with palytoxin and karlotoxin increasing in significance. The potential for tetrodotoxin, maitotoxin and palytoxin to contaminate seafood is also of concern, warranting future investigation. The largest and most significant toxic bloom in Tasmania in 2012 resulted in an estimated total economic loss of~AUD$23M, indicating that there is an imperative to improve toxin and organism detection methods, clarify the toxin profiles of species of phytoplankton and carry out both intra‐ and inter‐species toxicity comparisons. Future work also includes the application of rapid, real‐time molecular assays for the detection of harmful species and toxin genes. This information, in conjunction with a better understanding of the life histories and ecology of harmful bloom species, may lead to more appropriate management of environmental, health and economic resources.

Ostreopsis cf. ovata is a benthic marine dinoflagellate, which blooms in summer along the coasts of the Mediterranean Sea, including many Italian regions since early 1990s. In tropical areas O. cf. ovata produces mainly palytoxins whereas in the Mediterranean basin it produces ovatoxins, and only trace amounts of a putative palytoxin. The toxicological profile of ovatoxins is still unknown. This paper describes the update of the Italian guidelines for the management of O. cf. ovata blooms related to bathing and recreational activities. The rationale for the guidelines starts from the current scientific knowledge on chemical, toxicological, and epidemiological aspects and on its diffusion, which are briefly summarized in the first part of the paper. On this basis a risk-based approach is developed, with the purpose to protect people from oral, dermal and inhalation exposure (the ones that so far caused major health problems), taking into account also the weather and sea conditions, which are crucial for the onset of blooms. Accordingly, the guidelines provide information on what indicators are needed to set up environmental monitoring activities and actions to take during diverse phases. They also outline a multi-step health surveillance system, and a system of communication to the public. Finally the still important scientific gaps and research needs are highlighted. [ABSTRACT FROM AUTHOR]

Palytoxin (PLTX), one the most potent marine toxins, and/or its analogs, have been identified in different marine organisms, such as Palythoa soft corals, Ostreopsis dinoflagellates, and Trichodesmium cyanobacteria. Although the main concern for human health is PLTXs entrance in the human food chain, there is growing evidence of adverse effects associated with inhalational, cutaneous, and/or ocular exposure to aquarium soft corals contaminated by PLTXs or aquaria waters. Indeed, the number of case reports describing human poisonings after handling these cnidarians is continuously increasing. In general, the signs and symptoms involve mainly the respiratory (rhinorrhea and coughing), skeletomuscular (myalgia, weakness, spasms), cardiovascular (electrocardiogram alterations), gastrointestinal (nausea), and nervous (paresthesia, ataxia, tremors) systems or apparates. The widespread phenomenon, the entity of the signs and symptoms of poisoning and the lack of control in the trade of corals as aquaria decorative elements led to consider these poisonings an emerging sanitary problem. This review summarizes literature data on human poisonings due to, or ascribed to, PLTX-containing soft corals, focusing on the different PLTX congeners identified in these organisms and their toxic potential.

Harmful Algal Blooms (HABs) are massive proliferations of toxic algal species that occur under appropriate climatic and environmental conditions. HABs can exert their adverse impacts both on the environment and on particular living organisms through the production of marine biotoxins. Consumption of contaminated seafood or direct exposure to marine biotoxins (swimming, aerosols etc.) can result in human illness or even death. Thousands of cases of marine-toxin-related human poisoning are reported every year on a global basis. In Italy, research on marine biotoxins has shown a continuously changing toxin profile, with most of the toxin classes known so far being found at some point in seafood and seawater. Starting in the late 1980s, with the first finding of a marine biotoxin, okadaic acid, along the Italian coastline, a number of other classes of marine toxins - namely, yessotoxins, pectenotoxins, saxitoxins, domoic acid, spirolides, palytoxins and azaspiracids - have been found. Here we provide an overview, in chronological order, of the many classes of marine biotoxins that have infested Italian seawater over the past 25 years. [ABSTRACT FROM AUTHOR]

Highlights: [•] 15 species of edible marine organisms sampled on 4 sites on the French Mediterranean coast were analysed for PlTXs. [•] Herbivorous and omnivorous species were more contaminated than carnivorous ones. [•] The major components of the toxin profile were OVTX-a (90%) and PlTX. [•] Occasionally the toxin content in the whole flesh was higher than 30μg PlTX+OVTX-a/kg meat. [•] Toxins were sequestered in the digestive tube and not in the remaining tissue or in the roe. [Copyright &y& Elsevier]

Abstract: The genus Ostreopsis includes several species capable of producing various palytoxin-like compounds which have harmful effects on humans and marine fauna. Species in this genus are regular members of the epiphytic community in tropical seas but their geographic range have shown an apparent expansion towards temperate regions in recent years. This is the case of the Mediterranean Sea, where Ostreopsis cf. ovata is responsible for intense blooms in summer and autumn. With the aim of describing the growth performances of O. cf. ovata, we carried out a multifactorial experiment in which strains isolated from 3 locations along the Italian coast were grown at different combinations of temperature, daylength and irradiance encompassing different seasonal conditions. Temperature constrained growth of O. cf. ovata within a window of 18–30°C, while best performances were recorded at 22 and 26°C. Growth was maximum at 12h daylength, whereas it was limited by photon flux density at short daylength (9h) and often showed photosaturation at the longest daylength (15h). Cells with anomalous shape were found during the exponential phase at the lowest and highest temperatures, while cells with a reduced size were produced at all conditions except 18°C. Total toxin concentration varied between the different environmental conditions and between exponential and post-exponential growth phases without a clear pattern, whereas toxin composition was less variable. Our results suggest that O. cf. ovata is adapted to intermediate temperatures and daylength conditions such as those recorded in the natural environment at the beginning of summer and/or at the beginning of autumn, when this dinoflagellate builds up its biomass along the coast of the Mediterranean Sea. Photosaturation instead occurs at the highest temperature and irradiance conditions, thus supporting the observations of generally lower cell abundances in late July–August. [Copyright &y& Elsevier]

Abstract: Intense blooms of the benthic dinoflagellate Ostreopsis cf. ovata have occurred in the northern Adriatic Sea since 2006. These blooms are associated with noxious effects on human health and with the mortality of benthic organisms because of the production of palytoxin-like compounds. The O. cf. ovata bloom and its relationships with nutrient concentrations at two stations on the Conero Riviera (northern Adriatic Sea) were investigated in the summer of 2009. O. cf. ovata developed from August to November, with the highest abundances in September (1.3×106 cellsg−1 fw corresponding to 63.8×103 cellscm−2). The presence of the single O. cf. ovata genotype was confirmed by a PCR assay. Bloom developed when the seawater temperature was decreasing. Nutrient concentrations did not seem to affect bloom dynamics. Toxin analysis performed by high resolution liquid chromatography–mass spectrometry revealed a high total toxin content (up to 75pgcell−1), including putative palytoxin and all the ovatoxins known so far. [Copyright &y& Elsevier]

Abstract: The state of the art of LC-MS of palytoxin and its analogues is reported in the present review. MS data for palytoxin, 42-hydroxy-palytoxin, ostreocin-D, mascarenotoxins, and ovatoxins, obtained using different ionization techniques, namely fast-atom bombardment (FAB), matrix assisted laser desorption ionization (MALDI), and electrospray ionization (ESI), are summarized together with the LC-MS methods used for their detection. Application of the developed LC-MS methods to both plankton and seafood analysis is also reported, paying attention to the extraction procedures used and to limits of detection (LOD) and quantitation (LOQ) achieved. In a research setting, LC-MS has shown a good potential in determination of palytoxin and its analogues from various sources, but, in a regulatory setting, routine LC-MS analysis of palytoxins is still at a preliminary stage. The LOQ currently achieved in seafood analysis appears insufficient to detect palytoxins in shellfish extract at levels close to the tolerance limit for palytoxins (30 μg/kg) proposed by the European Food Safety Authority (). In addition, lacking of certified reference standard of palytoxins as well as of validation studies for the proposed LC-MS methods represent important issues that should be faced for future perspectives of LC-MS technique. [Copyright &y& Elsevier]