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Global ocean temperatures are rising, yet the impacts of such changes on harmful algal blooms (HABs) are not fully understood. Here we used high-resolution sea-surface temperature records (1982 to 2016) and temperature-dependent growth rates of two algae that produce potent biotoxins, Alexandrium fundyense and Dinophysis acuminata, to evaluate recent changes in these HABs. For both species, potential mean annual growth rates and duration of bloom seasons significantly increased within many coastal Atlantic regions between 40°N and 60°N, where incidents of these HABs have emerged and expanded in recent decades. Widespread trends were less evident across the North Pacific, although regions were identified across the Salish Sea and along the Alaskan coastline where blooms have recently emerged, and there have been significant increases in the potential growth rates and duration of these HAB events. We conclude that increasing ocean temperature is an important factor facilitating the intensification of these, and likely other, HABs and thus contributes to an expanding human health threat.

Marine biotoxins are produced by aquatic microorganisms and accumulate in shellfish or finfish following the food web. These toxins usually reach human consumers by ingestion of contaminated seafood, although other exposure routes like inhalation or contact have also been reported and may cause serious illness. This review shows the current data regarding the symptoms of acute intoxication for several toxin classes, including paralytic toxins, amnesic toxins, ciguatoxins, brevetoxins, tetrodotoxins, diarrheic toxins, azaspiracids and palytoxins. The information available about chronic toxicity and relative potency of different analogs within a toxin class are also reported. The gaps of toxicological knowledge that should be studied to improve human health protection are discussed. In general, gathering of epidemiological data in humans, chronic toxicity studies and exploring relative potency by oral administration are critical to minimize human health risks related to these toxin classes in the near future.

Prorocentrum, a dinoflagellate responsible for producing diarrhetic shellfish poisoning (DSP) toxins, poses significant threats to marine ecosystems, aquaculture industries, and human health. DSP toxins, including okadaic acid (OA), dinophysis toxin (DTX), and their diverse derivatives, continue to be identified and characterized. In this study, we report the isolation of four new diol esters of OA/DTX-1 from large-scale cultures of Prorocentrum lima. Their chemical structures were elucidated through comprehensive NMR and MS analyses, along with structural comparisons with the well-known OA. Notably, compound 1 featured an additional ester group within the diol unit, while compound 2 was revealed to be a C11 diol ester. The cytotoxicity of these newly isolated derivatives was evaluated against three cell lines: Neuro2a (mouse), HCT116 (human), and HepG2 (human). All diol esters exhibited cytotoxic effects, with compound 3 displaying toxicity comparable to OA. These results expand our understanding of DSP toxin diversity and provide valuable insight into the structural variations and biological activity of diol esters of OA/DTX-1.

Background/Aims: Okadaic acid (OA) and the structurally related compounds dinophysistoxin-1 (DTX1) and dinophysistoxin-2 (DTX2) are marine phycotoxins that cause diarrheic shellfish poisoning (DSP) in humans due to ingestion of contaminated shellfish. In order to guarantee consumer protection, the regulatory authorities have defined the maximum level of DSP toxins as 160 µg OA equivalent kg -1 shellfish meat. For risk assessment and overall toxicity determination, knowledge of the relative toxicities of each analogue is required. In absence of enough information from human intoxications, oral toxicity in mice is the most reliable data for establishing Toxicity Equivalence Factors (TEFs). Methods: Toxins were administered to mice by gavage, after that the symptomatology and mice mortality was registered over a period of 24 h. Organ damage data were collected at necropsy and transmission electron microscopy (TEM) was used for ultrastructural studies. Toxins in urine, feces and blood were analyzed by HPLC-MS/MS. The evaluation of in vitro potencies of OA, DTX1 and DTX2 was performed by the protein phosphatase 2A (PP2A) inhibition assay. Results: Mice that received DSP toxins by gavage showed diarrhea as the main symptom. Those toxins caused similar gastrointestinal alterations as well as intestine ultrastructural changes. However, DSP toxins did not modify tight junctions to trigger diarrhea. They had different toxicokinetics and toxic potency. The lethal dose 50 (LD 50 ) was 487 µg kg -1 bw for DTX1, 760 µg kg -1 bw for OA and 2262 µg kg -1 bw for DTX2. Therefore, the oral TEF values are: OA = 1, DTX1 = 1.5 and DTX2 = 0.3. Conclusion: This is the first comparative study of DSP toxins performed with accurate well-characterized standards and based on acute toxicity data. Results confirmed that DTX1 is more toxic than OA by oral route while DTX2 is less toxic. Hence, the current TEFs based on intraperitoneal toxicity should be modified. Also, the generally accepted toxic mode of action of this group of toxins needs to be reevaluated.

Diarrhetic shellfish-poisoning (DSP) toxins such as okadaic acid and dinophysistoxins harm the human gastrointestinal tract, and therefore, their levels are regulated to an upper limit of 160 μg per kg tissue to protect consumers. Rodents are used routinely for risk assessment and studies concerning mechanisms of toxicity, but there is a general move toward reducing and replacing vertebrates for these bioassays. We have adopted insect larvae of the wax moth Galleria mellonella as a surrogate toxicology model. We treated larvae with environmentally relevant doses of okadaic acid (80–400 μg/kg) via intrahaemocoelic injection or gavage to determine marine toxin-related health decline: (1) whether pre-exposure to a sub-lethal dose of toxin (80 μg/kg) enhances susceptibility to bacterial infection, or (2) alters tissue pathology and bacterial community (microbiome) composition of the midgut. A sub-lethal dose of okadaic acid (80 μg/kg) followed 24 h later by bacterial inoculation (2 × 105Escherichia coli) reduced larval survival levels to 47%, when compared to toxin (90%) or microbial challenge (73%) alone. Histological analysis of the midgut depicted varying levels of tissue disruption, including nuclear aberrations associated with cell death (karyorrhexis, pyknosis), loss of organ architecture, and gross epithelial displacement into the lumen. Moreover, okadaic acid presence in the midgut coincided with a shift in the resident bacterial population over time in that substantial reductions in diversity (Shannon) and richness (Chao-1) indices were observed at 240 μg toxin per kg. Okadaic acid-induced deterioration of the insect alimentary canal resembles those changes reported for rodent bioassays.

Type 2 diabetes has been associated with cognitive decline and an increased risk of neurodegenerative diseases, although the cellular mechanisms underlying this relationship remain unclear. We investigated whether high-glucose exposure induces neuronal damage and increases susceptibility to secondary oxidative and neurotoxic insults in vitro. SH-SY5Y cells were differentiated into neuron-like cells and exposed to increasing glucose concentrations. Based on the viability results, cells exposed to high glucose (HG; 100 mM, 120 h) were further analyzed and challenged with hydrogen peroxide (H 2 O 2 ) or okadaic acid (OA). Cell viability, DNA damage, mitochondrial superoxide production, cell cycle distribution, cell death, and gene expression were evaluated. Differentiation was confirmed by increased neurite length and expression of neuronal markers (β-III-tubulin and MAP2). High glucose reduced cell viability in a concentration- and time-dependent manner. HG exposure increased oxidative DNA damage, mitochondrial superoxide levels, and apoptosis, accompanied by reduced OGG1 gene expression. Combined treatments with HG and H 2 O 2 or OA further decreased cell viability and increased the sub-G1 fraction compared with controls and single treatments. These findings demonstrate that HG exerts cytotoxic and genotoxic effects and sensitizes neuron-like cells to subsequent oxidative and neurotoxic insults, thereby contributing to mechanisms underlying neuronal dysfunction and neurodegenerative processes.

is a widely distributed and major source of diarrhetic shellfish toxins (DSTs); the ecological impact of diol-estered DSTs (eDSTs) compounds on benthic systems is still inadequate. In this study, the acute toxicity of eDSTs was evaluated in , and their accumulation capacity and toxic effects were examined in for an ecological risk assessment. The results indicated that larvae 1 (L1) was more sensitive than larvae 4 (L4) of , and the eDSTs in extract lysate were more toxic than the okadaic acid (OA) standard solution. The lowest LC values were 0.293 and 0.469 μg/mL for L1 and L4, respectively. The growth, productivity, and intestinal permeability of were impaired, and the effect of extract lysate on was greater than that of the OA standard solution. The total toxin concentration in the digestive gland of mussels reached 3230 μg/kg, with esterified DSTs accounting for 76.7-97.1% of total toxins and inducing marked oxidative stress. Diol-estered DSTs exert direct toxic effects, including oxidative damage and growth inhibition, while exhibiting a high accumulation potential. This study revealed the toxicity of eDSTs, necessitating a focused investigation to comprehensively assess their toxicological impact and ecological risks.

Okadaic acid (OKA), a polyether C38 fatty acid toxin extracted from a black sponge Hallichondria okadaii , is a potent and selective inhibitor of protein phosphatase, PP1 and PP2A. OKA has been proved to be a powerful probe for studying the various regulatory mechanisms and neurotoxicity. Because of its property to inhibit phosphatase activity, OKA is associated with protein phosphorylation; it is implicated in hyperphosphorylation of tau and in later stages causes Alzhiemer’s disease (AD)-like pathology. AD is a progressive neurodegenerative disorder, pathologically characterized by extracellular amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). The density of tau tangles in AD pathology is associated with cognitive dysfunction. Recent studies have highlighted the importance of serine/threonine protein phosphatases in many processes including apoptosis and neurotoxicity. Although OKA causes neurotoxicity by various pathways, the exact mechanism is still not clear. The activation of major kinases, such as Ser/Thr, MAPK, ERK, PKA, JNK, PKC, CaMKII, Calpain, and GSK3β, in neurons is associated with AD pathology. These kinases, associated with abnormal hyperphosphorylation of tau, suggest that the cascade of these kinases could exclusively be involved in the pathogenesis of AD. The activity of serine/threonine protein phosphatases needs extensive study as these enzymes are potential targets for novel therapeutics with applications in many diseases including cancer, inflammatory diseases, and neurodegeneration. There is a need to pay ample attention on MAPK kinase pathways in AD, and OKA can be a better tool to study cellular and molecular mechanism for AD pathology. This review elucidates the regulatory mechanism of PP2A and MAPK kinase and their possible mechanisms involved in OKA-induced apoptosis, neurotoxicity, and AD-like pathology.

Diarrheic shellfish toxins (DSTs), especially okadaic acid (OA) and its related compounds, are lipophilic marine biotoxins mainly synthesized by dinoflagellates of the genera Dinophysis and Prorocentrum. These compounds bioaccumulate in filter-feeding shellfish like mussels and clams, posing a considerable public health risk due to their strong gastrointestinal effects when contaminated seafood is consumed. This review offers a thorough overview of the current understanding of OA-group toxins with a focus on the molecular mechanisms of toxicity, including cytoskeletal disruption, apoptosis, inflammation, oxidative stress, and mitochondrial dysfunction. Additionally, their ecological impacts on aquatic organisms and patterns of bioaccumulation are explored. Recent advances in detection methods and regulatory frameworks are discussed, highlighting the necessity for robust monitoring systems to safeguard seafood safety. Enhanced knowledge of the toxicity, distribution, and fate of DSP (diarrheic shellfish poisoning) is essential for improving risk assessment and managing marine biotoxins. Despite methodological advances, gaps remain regarding chronic exposure and species-specific detoxification pathways.

As emerging contaminants, microplastics (MPs) may pose a threat to human health. Their co-exposure with the widespread phycotoxin okadaic acid (OA), a marine toxin known to cause gastrointestinal toxicity, may exacerbate health risk and raise public safety concern. In this study, the toxicity mechanisms of MPs and OA on intestinal microenvironment was explored using human Caco-2 cells as the model, which was combined with an in vitro fecal fermentation experiment. Our results showed that co-exposure to MPs (80 μg/mL) and OA (20 ng/mL) significantly decreased cell viability, increased intracellular reactive oxygen species (ROS) production, elevated lactate dehydrogenase release, impaired ABC transporter activity, promoted OA accumulation, and triggered inflammatory response compared to the control, MPs, and OA groups, indicating that co-exposure directly compromises intestinal epithelial integrity. In vitro fermentation experiments revealed that co-exposure disrupted gut microbial composition, decreasing the relative abundance of some bacteria, such as Parasutterella and Adlercreutzia, while increasing opportunistic pathogens, such as Escherichia-Shigella, increased. These findings provide new insights into the impact and underlying mechanisms of MPs and OA co-exposure on intestinal homeostasis, highlighting the potential health risks associated with MPs.