The stunting effect of an oxylipins-containing macroalgae extract on sea urchin reproduction and neuroblastoma cells viability.

Different bioactive molecules extracted from macroalgae, including oxylipins, showed interesting potentials in different applications, from healthcare to biomaterial manufacturing and environmental remediation. Thus far, no studies reported the effects of oxylipins-containing macroalgae extracts on embryo development of marine invertebrates and on neuroblastoma cancer cells. Here, the effects of an oxylipins-containing extract from Ericaria brachycarpa, a canopy-forming brown algae, were investigated on the development of Arbacia lixula sea urchin embryos and on SH-SY5Y neuroblastoma cells viability. Embryos and cells were exposed to concentrations covering a full 0-100% dose-response curve, with doses ranging from 0 to 40 µg mL-1 for embryos and from 0 to 200 µg mL-1 for cells. These natural marine toxins caused a dose-dependent decrease of normal embryos development and of neuroblastoma cells viability. Toxicity was higher for exposures starting from the gastrula embryonal stage if compared to the zygote and pluteus stages, with an EC50 significantly lower by 33 and 68%, respectively. Embryos exposed to low doses showed a general delay in development with a decrease in the ability to calcify, while higher doses caused 100% block of embryo growth. Exposure of SH-SY5Y neuroblastoma cells to 40 µg mL-1 for 72 h caused 78% mortality, while no effect was observed on their neuronal-like cells derivatives, suggesting a selective targeting of proliferating cells. Western Blot experiments on both model systems displayed the modulation of different molecular markers (HSP60, HSP90, LC3, p62, CHOP and cleaved caspase-7), showing altered stress response and enhanced autophagy and apoptosis, confirmed by increased fragmented DNA in apoptotic nuclei. Our study gives new insights into the molecular strategies that marine invertebrates use when responding to their environmental natural toxins and suggests the E. brachycarpa's extract as a potential source for the development of innovative, environmentally friendly products with larvicide and antineoplastic activity.

Peptide Toxins from Antarctica: The Nemertean Predator and Scavenger Parborlasia corrugatus (McIntosh, 1876).

Peptide toxins from marine invertebrates have found use as drugs and in biotechnological applications. Many marine habitats, however, remain underexplored for natural products, and the Southern Ocean is among them. Here, we report toxins from one of the top predators in Antarctic waters: the nemertean worm Parborlasia corrugatus (McIntosh, 1876). Transcriptome mining revealed a total of ten putative toxins with a cysteine pattern similar to that of alpha nemertides, four nemertide-beta-type sequences, and two novel full-length parborlysins. Nemertean worms express toxins in the epidermal mucus. Here, the expression was determined by liquid chromatography combined with mass spectrometry. The findings include a new type of nemertide, 8750 Da, containing eight cysteines. In addition, we report the presence of six cysteine-containing peptides. The toxicity of tissue extracts and mucus fractions was tested in an Artemia assay. Notably, significant activity was observed both in tissue and the high-molecular-weight mucus fraction, as well as in a parborlysin fraction. Membrane permeabilization experiments display the membranolytic activity of some peptides, most prominently the parborlysin fraction, with an estimated EC50 of 70 nM.

Advances in the Early Warning of Shellfish Toxification by Dinophysis acuminata.

In Western Europe, the incidence of DST is likely the highest globally, posing a significant threat with prolonged bans on shellfish harvesting, mainly caused by species of the dinoflagellate genus Dinophysis. Using a time series from 2014 to 2020, our study aimed (i) to determine the concentration of D. acuminata in water at which shellfish toxin levels could surpass the regulatory limit (160 µg OA equiv kg-1) and (ii) to assess the predictability of toxic events for timely mitigation actions, especially concerning potential harvesting bans. The analysis considered factors such as (i) overdispersion in the data, (ii) distinct periods of presence and absence, (iii) the persistence of cells, and (iv) the temporal lag between cells in the water and toxins in shellfish. Four generalized additive models were tested, with the Tweedie (TW-GAM) model showing superior performance (>85%) and lower complexity. The results suggest existing thresholds currently employed (200 and 500 cells L-1) are well-suited for the Portuguese coast, supported by empirical evidence (54-79% accuracy). The developed algorithm allows for thresholds to be tailored on a case-by-case basis, offering flexibility for regional variations.

Paralytic Shellfish Toxins in Mollusks from Galicia Analyzed by a Fast Refined AOAC 2005.06 Method: Toxicity, Toxin Profile, and Inter-Specific, Spatial, and Seasonal Variations.

Paralytic shellfish poisoning is an important concern for mollusk fisheries, aquaculture, and public health. In Galicia, NW Iberian Peninsula, such toxicity has been monitored for a long time using mouse bioassay. Therefore, little information exists about the precise toxin analogues and their possible transformations in diverse mollusk species and environments. After the change in the European PSP reference method, a refinement of the Lawrence method was developed, achieving a 75% reduction in chromatogram run time. Since the beginning of 2021, when this refinement Lawrence method was accredited under the norm UNE-EN ISO/IEC 17025, it has been used in the area to determine the toxin profiles and to estimate PSP toxicity in more than 4500 samples. In this study, we have summarized three years of monitoring results, including interspecific, seasonal, and geographical variability of PSP toxicity and toxin profile. PSP was detected in more than half of the samples analyzed (55%), but only 4.4% of the determinations were above the EU regulatory limit. GTX1,4 was the pair of STX analogs that produced the highest toxicities, but GTX2,3 was found in most samples, mainly due to the reduction of GTX1,4 but also by the higher sensitivity of the method for this pair of analogs. STX seems to be mainly a product of biotransformation from GTX2,3. The studied species (twelve bivalves and one gastropod) accumulated and transformed PSP toxins to a different extent, with most of them showing similar profiles except for Spisula solida and Haliotis tuberculata. Two seasonal peaks of toxicity were found: one in spring-early summer and another in autumn, with slightly different toxin profiles during outbreaks in relation to the toxicity during valleys. In general, both the total toxicity and toxin profiles of the southernmost locations were different from those in the northern part of the Atlantic coast and the Cantabrian Sea, but this general pattern is modified by the PSP history of some specific locations.

Exposure to microplastics renders immunity of the thick-shell mussel more vulnerable to diarrhetic shellfish toxin-producing harmful algae.

Despite both microplastics (MPs) and harmful algae blooms (HABs) may pose a severe threat to the immunity of marine bivalves, the toxification mechanism underlying is far from being fully understood. In addition, owing to the prevalence and sudden occurrence characteristics of MPs and HABs, respectively, bivalves with MP-exposure experience may face acute challenge of harmful algae under realistic scenarios. However, little is known about the impacts and underlying mechanisms of MP-exposure experience on the susceptibility of immunity to HABs in bivalve mollusks. Taking polystyrene MPs and diarrhetic shellfish toxin-producing Prorocentrum lima as representatives, the impacts of MP-exposure on immunity vulnerability to HABs were investigated in the thick-shell mussel, Mytilus coruscus. Our results revealed evident immunotoxicity of MPs and P. lima to the mussel, as evidenced by significantly impaired total count, phagocytic activity, and cell viability of haemocytes, which may result from the induction of oxidative stress, aggravation of haemocyte apoptosis, and shortage in cellular energy supply. Moreover, marked disruptions of immunity, antioxidant system, apoptosis regulation, and metabolism upon MPs and P. lima exposure were illustrated by gene expression and comparative metabolomic analyses. Furthermore, the mussels that experienced MP-exposure were shown to be more vulnerable to P. lima, indicated by greater degree of deleterious effects on abovementioned parameters detected. In general, our findings emphasize the threat of MPs and HABs to bivalve species, which deserves close attention and more investigation.

The Cyclic Imine Core Common to the Marine Macrocyclic Toxins Is Sufficient to Dictate Nicotinic Acetylcholine Receptor Antagonism.

Macrocyclic imine phycotoxins are an emerging class of chemical compounds associated with harmful algal blooms and shellfish toxicity. Earlier binding and electrophysiology experiments on nAChR subtypes and their soluble AChBP surrogates evidenced common trends for substantial antagonism, binding affinities, and receptor-subtype selectivity. Earlier, complementary crystal structures of AChBP complexes showed that common determinants within the binding nest at each subunit interface confer high-affinity toxin binding, while distinctive determinants from the flexible loop C, and either capping the nest or extending toward peripheral subsites, dictate broad versus narrow receptor subtype selectivity. From these data, small spiroimine enantiomers mimicking the functional core motif of phycotoxins were chemically synthesized and characterized. Voltage-clamp analyses involving three nAChR subtypes revealed preserved antagonism for both enantiomers, despite lower subtype specificity and binding affinities associated with faster reversibility compared with their macrocyclic relatives. Binding and structural analyses involving two AChBPs pointed to modest affinities and positional variability of the spiroimines, along with a range of AChBP loop-C conformations denoting a prevalence of antagonistic properties. These data highlight the major contribution of the spiroimine core to binding within the nAChR nest and confirm the need for an extended interaction network as established by the macrocyclic toxins to define high affinities and marked subtype specificity. This study identifies a minimal set of functional pharmacophores and binding determinants as templates for designing new antagonists targeting disease-associated nAChR subtypes.

Ultrastructural, molecular and haemato-immunological changes: Multifaceted toxicological effects of microcystin-LR in rohu, Labeo rohita.

No water body is resilient to afflicts of algal bloom, if goes unmanaged. With the increasing trend of intensification, eutrophication and climate change, Labeo rohita (rohu) is highly anticipated to suffer from the deleterious effects of bloom and eventually its toxins. A comprehensive study was conducted to understand the toxicopathological effects of microcystin-LR (MC-LR) in rohu following intraperitoneal injection of 96 h-LD50 dose i.e., 713 µg kg-1. Substantial changes in micro- and ultrastructural level were evident in histopathology and transmission electron microscope (TEM) study. The haematological, biochemical, cellular and humoral innate immune biomarkers were significantly altered (p < 0.05) in MC-LR treated fish. The mRNA transcript levels of IL-1ß, IL-10, IgM and IgZ in liver and kidney tissues were significantly up-regulated in 12 hpi and declined in 96 hpi MC-LR exposed fish. The relative mRNA expression of caspase 9 in the liver and kidney indicates mitochondrial-mediated apoptosis which was strongly supported by TEM study. In a nutshell, our study illustrates for the first time MC-LR induced toxicological implications in rohu displaying immunosuppression, enhanced oxidative stress, pathophysiology, modulation in mRNA transcription, genotoxicity, structural and ultrastructural alterations signifying it as a vulnerable species for MC-LR intoxication.

Alleviation of microcystin-leucine arginine -induced hepatotoxicity: An updated overview.

OBJECTIVES: Contamination of surface waters is a major health threat for all living creatures. Some types of blue-green algae that naturally occur in fresh water, are able to produce various toxins, like Microcystins (MCs). Microcystin-leucine arginine (MC-LR) produced by Microcystis aeruginosa is the most toxic and abundant isoforms of MCs, and it causes hepatotoxicity. The present article reviews preclinical experiments examined different treatments, including herbal derivatives, dietary supplements and drugs against MC-LR hepatotoxicity. METHODS: We searched scientific databases Web of Science, Embase, Medline (PubMed), Scopus, and Google Scholar using relevant keywords to find suitable studies until November 2023. RESULTS: MC-LR through Organic anion transporting polypeptide superfamily transporters (OATPs) penetrates and accumulates in hepatocytes, and it inhibits protein phosphatases (PP1 and PP2A). Consequently, MC-LR disturbs many signaling pathways and induces oxidative stress thus damages cellular macromolecules. Some protective agents, especially plants rich in flavonoids, and natural supplements, as well as chemoprotectants were shown to diminish MC-LR hepatotoxicity. CONCLUSION: The reviewed agents through blocking the OATP transporters (nontoxic nostocyclopeptide-M1, captopril, and naringin), then inhibition of MC-LR uptake (naringin, rifampin, cyclosporin-A, silymarin and captopril), and finally at restoration of PPAse activity (silybin, quercetin, morin, naringin, rifampin, captopril, azo dyes) exert hepatoprotective effect against MC-LR.

Can exposure to Gymnodinium catenatum toxic blooms influence the impacts induced by Neodymium in Mytilus galloprovincialis mussels? What doesn't kill can make them stronger?

The presence in marine shellfish of toxins and pollutants like rare earth elements (REEs) poses a major threat to human well-being, coastal ecosystems, and marine life. Among the REEs, neodymium (Nd) stands out as a widely utilized element and is projected to be among the top five critical elements by 2025. Gymnodinum catenatum is a phytoplankton species commonly associated with the contamination of bivalves with paralytic shellfish toxins. This study evaluated the biological effects of Nd on the mussel species Mytilus galloprovincialis when exposed to G. catenatum cells for fourteen days, followed by a recovery period in uncontaminated seawater for another fourteen days. After co-exposure, mussels showed similar toxin accumulation in the Nd and G. catenatum treatment in comparison with the G. catenatum treatment alone. Increased metabolism and enzymatic defenses were observed in organisms exposed to G. catenatum cells, while Nd inhibited enzyme activity and caused cellular damage. Overall, this study revealed that the combined presence of G. catenatum cells and Nd, produced positive synergistic effects on M. galloprovincialis biochemical responses compared to G. catenatum alone, indicating that organisms' performance may be significantly modulated by the presence of multiple co-occurring stressors, such those related to chemical pollution and harmful algal blooms. ENVIRONMENTAL IMPLICATIONS: Neodymium (Nd) is widely used in green technologies like wind turbines, and this element's potential threats to aquatic environments are almost unknown, especially when co-occurring with other environmental factors such as blooms of toxic algae. This study revealed the cellular impacts induced by Nd in the bioindicator species Mytilus galloprovincialis but further demonstrated that the combination of both stressors can generate a positive defense response in mussels. The present findings also demonstrated that the impacts caused by Nd lasted even after a recovery period while a previous exposure to the toxins generated a faster biochemical improvement by the mussels.

Sea Cucumber Viscera Contains Novel Non-Holostane-Type Glycoside Toxins that Possess a Putative Chemical Defense Function.

Sea cucumbers frequently expel their guts in response to predators and an aversive environment, a behavior perceived as releasing repellents involved in chemical defense mechanisms. To investigate the chemical nature of the repellent, the viscera of stressed sea cucumbers (Apostichopus japonicus) in the Yellow Sea of China were collected and chemically analyzed. Two novel non-holostane triterpene glycosides were isolated, and the chemical structures were elucidated as 3ꞵ-O-[ꞵ-D-glucopyranosyl-(1→2)-ꞵ-D-xylopyranosyl]-(20S)-hydroxylanosta-7,25-diene-18(16)-lactone (1) and 3ꞵ-O-[ꞵ-D-quinovopyranosyl-(1→2)-ꞵ-D-xylopyranosyl]-(20S)-hydroxylanosta-7,25-diene-18(16)-lactone (2) by spectroscopic and mass-spectrometric analyses, exemplifying a triterpene glycoside constituent of an oligosaccharide containing two sugar-units and a non-holostane aglycone. Zebrafish embryos were exposed to various doses of 1 and 2 from 4 to 96 hpf. Compound 1 exposure showed 96 h-LC50 41.5 µM and an increased zebrafish mortality rates in roughly in a dose- and time-dependent manner. Compound 2, with different sugar substitution, exhibited no mortality and moderate teratogenic toxicity with a 96 h-EC50 of 173.5 µM. Zebrafish embryos exhibited teratogenic effects, such as reduced hatchability and total body length. The study found that triterpene saponin from A. japonicus viscera had acute toxicity in zebrafish embryos, indicating a potential chemical defense role in the marine ecosystem.

Consumption of toxic benthic cyanobacteria by two common demersal fish: Growth, antioxidant and liver histopathology responses.

Benthic freshwater cyanobacteria have the potential to produce toxins. Compared with more extensively studied plankton species, little is known about the impact of harmful benthic cyanobacteria on aquatic organisms. As demersal fish are usually in direct contact with benthic cyanobacteria, it is important to understand their interactive effects. This study investigated the physio-chemical responses of two demersal fish (Xenocypris davidi and Crucian carp) after exposure to benthic Oscillatoria (producing cylindrospermopsin, 2 × 106 cells/mL) for 7 days. Interestingly, benthic Oscillatoria had less adverse effects on X. davidi than C. carp. The two demersal fish effectively ingested Oscillatoria, but Oscillatoria cell sheathes could not be fully digested in C. carp intestines and led to growth inhibition. Oscillatoria consumption induced oxidative stress and triggered alterations in detoxification enzyme activities in the X. davidi liver. Superoxide dismutase (SOD) and glutathione reductase (GR) activities significantly increased in the C. carp liver, but catalase (CAT) and detoxification enzymes glutathione S-transferase (GST) and glutathione (GSH) activities were insignificantly changed. This suggested that C. carp may have a relatively weak detoxification capacity for toxic Oscillatoria. Oscillatoria ingestion led to more pronounced liver pathological changes in C. carp, including swelling, deformation, and loss of cytoskeleton structure. Simultaneously, fish consumption of Oscillatoria increased extracellular cylindrospermopsin concentration. These results provide valuable insights into the ecological risks associated with benthic cyanobacteria in aquatic ecosystems.

Potential roles of hydroxybenzoate paralytic shellfish toxins in modulating toxin biokinetics in scallops.

Paralytic shellfish toxins (PSTs) produced by some marine dinoflagellates can cause severe human intoxication via vectors like bivalves. Toxic dinoflagellate Gymnodinium catenatum produce a novel group of hydroxybenzoate PSTs named GC toxins, but their biokinetics in bivalves haven't been well examined. In this experiment, we analyzed PSTs in bay scallops Argopecten irradians exposed to G. catenatum (strain MEL11) to determine their accumulation, elimination, anatomical distribution, and biotransformation. To our surprise, up to 30% of the PSTs were accumulated in the adductor muscle of scallops at the end of the experiment, and the toxicity of adductor muscle exceeded the regulatory limit of 800 µg STXeq/kg in only 6 days. High concentration of toxins in the adductor muscle are likely linked to the rapid transfer of GC toxins from viscera to other tissues. Moreover, most GC toxins in scallops were found rapidly transformed to decarbamoyl toxins through enzyme-mediated hydrolysis, which was further supported by the in vitro incubation experiments. Our study demonstrates that GC toxins actively participate in toxin distribution and transformation in scallops, which may increase the risks of food poisoning associated with the consumption of scallop adductor muscle. ENVIRONMENTAL IMPLICATION: The negative impacts of harmful algal blooms (HABs) have become a global environmental concern under the joint effects of cultural eutrophication and climate change. Our study, targeted on the biokinetics of paralytic shellfish toxins in scallops exposed to Gymnodinium catenatum producing unique GC toxins, aims to elucidate potential risks of seafood poisoning associated with GC toxins. The findings of this study will help us to understand the roles of GC toxins in seafood poisoning, and to develop effective management strategies against toxic algal blooms and phycotoxins.

Pubertal exposure to Microcystin-LR arrests spermatogonia proliferation by inducing DSB and inhibiting SIRT6 dependent DNA repair in vivo and in vitro.

The reproduction toxicity of pubertal exposure to Microcystin-LR (MC-LR) and the underlying mechanism needs to be further investigated. In the current study, pubertal male ICR mice were intraperitoneally injected with 2 µg/kg MC-LR for four weeks. Pubertal exposure to MC-LR decreased epididymal sperm concentration and blocked spermatogonia proliferation. In-vitro studies found MC-LR inhibited cell proliferation of GC-1 cells and arrested cell cycle in G2/M phase. Mechanistically, MC-LR exposure evoked excessive reactive oxygen species (ROS) and induced DNA double-strand break in GC-1 cells. Besides, MC-LR inhibited DNA repair by reducing PolyADP-ribosylation (PARylation) activity of PARP1. Further study found MC-LR caused proteasomal degradation of SIRT6, a monoADP-ribosylation enzyme which is essential for PARP1 PARylation activity, due to destruction of SIRT6-USP10 interaction. Additionally, MG132 pretreatment alleviated MC-LR-induced SIRT6 degradation and promoted DNA repair, leading to the restoration of cell proliferation inhibition. Correspondingly, N-Acetylcysteine (NAC) pre-treatment mitigated the disturbed SIRT6-USP10 interaction and SIRT6 degradation, causing recovered DNA repair and subsequently restoration of cell proliferation inhibition in MC-LR treated GC-1 cells. Together, pubertal exposure to MC-LR induced spermatogonia cell cycle arrest and sperm count reduction by oxidative DNA damage and simultaneous SIRT6-mediated DNA repair failing. This study reports the effect of pubertal exposure to MC-LR on spermatogenesis and complex mechanism how MC-LR induces spermatogonia cell proliferation inhibition.

Microcystin-LR sensitizes the Oncorhynchus mykiss intestinal epithelium and interacts with paralytic shellfish toxins to alter oxidative balance.

In the context of harmful algal blooms, fish can be exposed to the combined effects of more than one toxin. We studied the effects of consecutive exposure to Microcystin-LR (MCLR) in vivo and paralytic shellfish toxins (PST) ex vivo/in vitro (MCLR+PST) in the rainbow trout Oncorhynchus mykiss's middle intestine. We fed juvenile fish with MCLR incorporated in the feed every 12 h and euthanized them 48 h after the first feeding. Immediately, we removed the middle intestine to make ex vivo and in vitro preparations and exposed them to PST for one hour. We analyzed glutathione (GSH) and glutathione disulfide (GSSG) contents, glutathione S-transferase (GST), glutathione reductase (GR), catalase (CAT), and protein phosphatase 1 (PP1) activities in ex vivo intestinal strips; apical and basolateral ATP-biding cassette subfamily C (Abcc)-mediated transport in ex vivo everted and non- everted sacs; and reactive oxygen species (ROS) production in isolated enterocytes in vitro. MCLR+PST treatment decreased the GSH content, GSH/GSSG ratio, GST activity, and increased ROS production. GR activity remained unchanged, while CAT activity only increased in response to PST. MCLR inhibited PP1 activity and activated Abcc-mediated transport only at the basolateral side of the intestine. Our results show a combined effect of MCLR+PST on the oxidative balance in the O. mykiss middle intestine, which is not affected by the two toxins groups when applied individually. Basolateral Abcc transporters activation by MCLR treatment could lead to an increase in the absorption of toxicants (including MCLR) into the organism. Therefore, MCLR makes the O. mykiss middle intestine more sensitive to possibly co-occurring cyanotoxins like PST.

Precautions for seafood consumers: An updated review of toxicity, bioaccumulation, and rapid detection methods of marine biotoxins.

Seafood products are globally consumed, and there is an increasing demand for the quality and safety of these products among consumers. Some seafoods are easily contaminated by marine biotoxins in natural environments or cultured farming processes. When humans ingest different toxins accumulated in seafood, they may exhibit different poisoning symptoms. According to the investigations, marine toxins produced by harmful algal blooms and various other marine organisms mainly accumulate in the body organs such as liver and digestive tract of seafood animals. Several regions around the world have reported incidents of seafood poisoning by biotoxins, posing a threat to human health. Thus, most countries have legislated to specify the permissible levels of these biotoxins in seafood. Therefore, it is necessary for seafood producers and suppliers to conduct necessary testing of toxins in seafood before and after harvesting to prohibit excessive toxins containing seafood from entering the market, which therefore can reduce the occurrence of seafood poisoning incidents. In recent years, some technologies which can quickly, conveniently, and sensitively detect biological toxins in seafood, have been developed and validated, these technologies have the potential to help seafood producers, suppliers and regulatory authorities. This article reviews the seafood toxins sources and types, mechanism of action and bioaccumulation of marine toxins, as well as legislation and rapid detection technologies for biotoxins in seafood for official and fishermen supervision.

Response of the toxic dinoflagellate Alexandrium minutum to exudates of the eelgrass Zostera marina.

Biotic interactions are a key factor in the development of harmful algal blooms. Recently, a lower abundance of planktonic dinoflagellates has been reported in areas dominated by seagrass beds, suggesting a negative interaction between both groups of organisms. The interaction between planktonic dinoflagellates and marine phanerogams, as well as the way in which bacteria can affect this interaction, was studied in two experiments using a non-axenic culture of the toxic dinoflagellate Alexandrium minutum exposed to increasing additions of eelgrass (Zostera marina) exudates from old and young leaves and to the presence or absence of antibiotics. In these experiments, A. minutum abundance, growth rate and photosynthetic efficiency (Fv/Fm), as well as bacterial abundance, were measured every 48 h. Toxin concentration per cell was determined at the end of both experiments. Our results demonstrated that Z. marina exudates reduced A. minutum growth rate and, in one of the experiments, also the photosynthetic efficiency. These results are not an indirect effect mediated by the bacteria in the culture, although their growth modify the magnitude of the negative impact on the dinoflagellate growth rate. No clear pattern was observed in the variation of toxin production with the treatments.

Effects of marine biotoxins on drug-metabolizing cytochrome P450 enzymes and their regulation in mammalian cells.

Marine biotoxins are a heterogenous group of natural toxins, which are able to trigger different types of toxicological responses in animals and humans. Health effects arising from exposure to marine biotoxins are ranging, for example, from gastrointestinal symptoms to neurological effects, depending on the individual toxin(s) ingested. Recent research has shown that the marine biotoxin okadaic acid (OA) can strongly diminish the expression of drug-metabolizing cytochrome P450 (CYP) enzymes in human liver cells by a mechanism involving proinflammatory signaling. By doing so, OA may interfere with the metabolic barrier function of liver and intestine, and thus alter the toxico- or pharmacokinetic properties of other compounds. Such effects of marine biotoxins on drug and xenobiotic metabolism have, however, not been much in the focus of research yet. In this review, we present the current knowledge on the effects of marine biotoxins on CYP enzymes in mammalian cells. In addition, the role of CYP-regulating nuclear receptors as well as inflammatory signaling in the regulation of CYPs by marine biotoxins is discussed. Strong evidence is available for effects of OA on CYP enzymes, along with information about possible molecular mechanisms. For other marine biotoxins, knowledge on effects on drug metabolism, however, is scarce.

Subcellular effects and lipid metabolism alterations in the gilthead seabream Sparus aurata fed on ovatoxins-contaminated mussels.

The marine microalgae Ostreopsis cf. ovata are a well-known producer of palytoxin (PlTXs) analogues, i.e. ovatoxins (OVTXs) among others, which arouse concern for animal and human health. Both in field and laboratory studies, presence of OVTXs, detected in species directly feeding on O. cf. ovata, was frequently correlated with impairment on organisms' physiology, development and behaviour, while similar knowledge is still lacking for animals feeding on contaminated preys. In this study, transfer and toxicity of OVTXs were evaluated in an exposure experiment, in which gilthead seabream Sparus aurata was fed with bivalve mussel Mytilus galloprovincialis, contaminated by a toxic strain of O. cf. ovata. Mussels exposed to O. cf. ovata for 21 days accumulated meanly 188 ± 13 µg/kg OVTXs in the whole tissues. Seabreams fed with OVTX-contaminated mussels started to reject the food after 6 days of contaminated diet. Although no detectable levels of OVTXs were measured in muscle, liver, gills and gastro-intestinal tracts, the OVTX-enriched diet induced alterations of lipid metabolism in seabreams livers, displaying a decreased content of total lipid and fatty acid, together with overexpression of fatty acid biosynthetic genes, downregulation of ß-oxidation genes and modulation of several genes related to lipid transport and regulation. Results from this study would suggest the hypothesis that OVTXs produced by O. cf. ovata may not be subject to bioaccumulation in fish fed on contaminated preys, being however responsible of significant biological effects, with important implications for human consumption of seafood products.

A review of poisoning with various types of biotoxins and its common clinical symptoms.

INTRODUCTION: Biotoxins are toxic substances that originate from living organisms and are harmful to humans. Therefore, we need to know the symptoms of biotoxins poisoning to manage the damage. The purpose of this study is to establish a practical diagnostic protocol for dealing with poisoned patients exposed to biotoxins. MATERIALS AND METHODS: The present study is a review study. Our studied community is articles and books matching the title of the project and relevant keywords. First, by searching the key words sign, symptom, biotoxins, relevant articles were extracted and studied from valid databases. By reviewing the studies based on the search strategy, four groups of biotoxins that were studied the most were identified. These four groups are marine biotoxins, bacterial biotoxins, fungal biotoxins and plant biotoxins. In each of these biotoxin groups, important toxins were selected and studied. RESULTS: A total of 1864 articles were initially identified from the databases searched in present study. After screening titles and abstracts, 26 articles were included in the systematic review. Specifically, 7 articles were included for bacterial toxins, 9 articles for marine toxins, 5 articles for plant toxins and 5 articles for fungal toxins. CONCLUSION: The symptoms of plant biotoxins poisoning may include cardiovascular, hematologic, neurologic, respiratory, renal, and gastrointestinal symptoms, while the symptoms of fungal biotoxins poisoning may include hepatic, renal, gastrointestinal, musculoskeletal, metabolic, respiratory, neurological, and cardiovascular symptoms. marine biotoxins poisoning presents with gastrointestinal and neurological symptoms, with varying incubation periods and recovery times. bacterial biotoxins exposure can lead to a wide range of clinical symptoms, with diarrhea, vomiting, and abdominal pain being the most common, and hemoglobinuria or hematuria being a sensitive and specific clinical manifestation for diagnosing ongoing HUS in children.

Current Research Status of Azaspiracids.

The presence and impact of toxins have been detected in various regions worldwide ever since the discovery of azaspiracids (AZAs) in 1995. These toxins have had detrimental effects on marine resource utilization, marine environmental protection, and fishery production. Over the course of more than two decades of research and development, scientists from all over the world have conducted comprehensive studies on the in vivo metabolism, in vitro synthesis methods, pathogenic mechanisms, and toxicology of these toxins. This paper aims to provide a systematic introduction to the discovery, distribution, pathogenic mechanism, in vivo biosynthesis, and in vitro artificial synthesis of AZA toxins. Additionally, it will summarize various detection methods employed over the past 20 years, along with their advantages and disadvantages. This effort will contribute to the future development of rapid detection technologies and the invention of detection devices for AZAs in marine environmental samples.