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1.
Environ Sci Pollut Res Int ; 31(45): 56578-56592, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39277832

ABSTRACT

Irrigation of crops with cyanotoxin-contaminated water poses a significant risk to human health. The direct phytotoxic effects of microcystin-LR (MC-LR), one of the most toxic and prevalent microcystin variants in water bodies, can induce physiological stress and hinder crop development and production. This study investigated the impact of environmentally relevant concentrations of MC-LR (1 to 10 µg L-1) on photosynthetic parameters and antioxidant response of lettuce (Lactuca sativa L.) and arugula (Eruca sativa L.) following irrigation with contaminated water. During the 15-day experiment, lettuce and arugula were exposed to various concentrations of MC-LR, and their photosynthetic rates, stomatal conductance, leaf tissue transpiration, and intercellular CO2 concentrations were measured using an infrared gas analyzer. These results suggest that the influence of MC-LR on gas exchange in crops is concentration-dependent, with notable disruptions during exposure and recovery tendency during detoxification. Antioxidant response analysis revealed that glutathione S-transferase (GST) and superoxide dismutase (SOD) activities were upregulated during the exposure phase in the presence of MC-LR. However, GST activity decreased during the detoxification phase in both crops, although the effects of the toxin at 10 µg L-1 were still evident in arugula. The internal H2O2 concentration in the crops increased after exposure to MC-LR, showing a time- and concentration-dependent pattern, with an increase during the exposure phase (days 1-7) and a decrease during the detoxification phase (days 8-15). Irrigation of lettuce and arugula with MC-LR-contaminated water affected various aspects of the photosynthetic apparatus and antioxidant responses, which could influence the general health and productivity of exposed crops at environmentally relevant microcystin concentrations. Furthermore, investigation of additional vegetable species and long-term MC-LR exposure can be crucial for understanding the extent of contamination risk, detoxification mechanisms, and other parameters affecting these crops.


Subject(s)
Antioxidants , Lactuca , Microcystins , Photosynthesis , Lactuca/drug effects , Photosynthesis/drug effects , Antioxidants/metabolism , Microcystins/toxicity , Marine Toxins , Agricultural Irrigation
2.
Proc Natl Acad Sci U S A ; 121(40): e2319177121, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39298472

ABSTRACT

In 2015, the largest recorded harmful algal bloom (HAB) occurred in the Northeast Pacific, causing nearly 100 million dollars in damages to fisheries and killing many protected marine mammals. Dominated by the toxic diatom Pseudo-nitzschia australis, this bloom produced high levels of the neurotoxin domoic acid (DA). Through molecular and transcriptional characterization of 52 near-weekly phytoplankton net-tow samples collected at a bloom hotspot in Monterey Bay, California, we identified active transcription of known DA biosynthesis (dab) genes from the three identified toxigenic species, including P. australis as the primary origin of toxicity. Elevated expression of silicon transporters (sit1) during the bloom supports the previously hypothesized role of dissolved silica (Si) exhaustion in contributing to bloom physiology and toxicity. We find that coexpression of the dabA and sit1 genes serves as a robust predictor of DA one week in advance, potentially enabling the forecasting of DA-producing HABs. We additionally present evidence that low levels of iron could have colimited the diatom population along with low Si. Iron limitation represents an overlooked driver of both toxin production and ecological success of the low-iron-adapted Pseudo-nitzschia genus during the 2015 bloom, and increasing pervasiveness of iron limitation may fuel the escalating magnitude and frequency of toxic Pseudo-nitzschia blooms globally. Our results advance understanding of bloom physiology underlying toxin production, bloom prediction, and the impact of global change on toxic blooms.


Subject(s)
Diatoms , Harmful Algal Bloom , Kainic Acid , Phytoplankton , Kainic Acid/analogs & derivatives , Kainic Acid/metabolism , Diatoms/genetics , Diatoms/metabolism , Diatoms/growth & development , Phytoplankton/genetics , Phytoplankton/metabolism , California , Marine Toxins/biosynthesis , Marine Toxins/genetics , Marine Toxins/metabolism , Neurotoxins/genetics , Neurotoxins/toxicity , Neurotoxins/metabolism , Iron/metabolism
3.
Harmful Algae ; 138: 102708, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39244226

ABSTRACT

Domoic acid (DA) is a dangerous phycotoxin produced by several strains of diatoms of the genus Pseudo-nitzschia, and responsible for Amnesic Shellfish Poisoning (ASP) in humans. The increasingly intense ASP-outbreaks along the English Channel over the last three decades have forced persistent harvest closures of economically important and highly contaminated bivalve stocks exhibiting slow DA-depuration rates, like the king scallop Pecten maximus. Under this scenario, other pectinid species, such as the queen scallop Aequipecten opercularis have been empirically proposed as alternative resources to redress the high economic losses due to the banning of the exploitation of P. maximus. Nevertheless, the kinetics of DA depuration in A. opercularis have not been assessed so far, and its direct extraction after ASP-episodes could represent a serious threat to public health. Hence, the main objective of this work was to estimate the DA-depuration rate in the digestive gland (DG) of naturally contaminated scallops A. opercularis after a toxic Pseudo-nitzschia australis bloom subjected to experimental depuration in the laboratory for 30 days. This study also intended to go further in the knowledge about the anatomical distribution of DA in scallop tissues, and corroborate the implications of autophagy in DA-sequestration in the DG of this species as recently hypothesized. In the DG, the DA-depuration rate (0.018 day-1) suggested that even with toxin burdens as low as 40 mg⋅kg-1 in the DG, queen scallops may remain contaminated for about 70 days, thus longer under intensely contamination scenarios. The subcellular analyses corroborated DA-sequestration mainly through late-autophagy within residual bodies in the DG, without differences in the frequencies of anti-DA labeled residual bodies across the entire depuration process. These results revealed that A. opercularis cannot be considered a fast DA-depurator, and represent a baseline knowledge for decision-making about harvesting natural beds of queen scallops after toxic Pseudo-nitzschia blooms. The findings of this work also represent a cornerstone for further research to accelerate DA-depuration in this species.


Subject(s)
Kainic Acid , Pectinidae , Kainic Acid/analogs & derivatives , Kainic Acid/metabolism , Pectinidae/physiology , Animals , Marine Toxins/analysis , Marine Toxins/metabolism , Diatoms/physiology , Diatoms/metabolism , Shellfish Poisoning , Harmful Algal Bloom
4.
Harmful Algae ; 138: 102697, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39244232

ABSTRACT

A variety of shellfish toxin-producing Harmful Algal Blooms (HABs) occur every year in coastal temperate waters worldwide. These toxic HABs may cause lengthy (months) harvesting bans of mussels and other suspension feeding bivalves exposed to their blooms. To safeguard public health and the shellfish industry, European Union regulations request periodic monitoring of potentially toxic microalgae in seawater and phycotoxins in live bivalve molluscs from shellfish production areas. Monitoring of other toxic microalgae, e.g., fish killers, is based solely on cell counts. Morphological identification and quantification of microalgal cells with light microscopy is time-consuming, requires a good expertise, and accurate identification to species level (e.g., Pseudo-nitzschia species) may require electron microscopy. Toxicity varies among morphologically similar species; there are toxic and non-toxic strains of the same species. Molecular techniques using ribosomal DNA sequences offer a possibility to identify and detect precisely the potentially toxic genus/species. In an earlier project (MIDTAL), specific probes against rRNA sequences of all HAB taxa, known at the time of the project, affecting shellfish areas worldwide were designed, and those affecting Europe were tested and calibrated against rRNA extracts of clonal cultures and field samples. Microarray technology was adopted to relate to cell numbers the fluorescence signal from the reaction of all target species probes spotted in the microarray slides with those present in a single sample extract. The EMERTOX project aimed to develop a more automatic "Lab on a chip" (LOC) technology, including a non- (cell) disruptive water concentration system and biosensors for HAB cells detection. Here, calibration curves are presented against toxic microalgae (cultures and field samples) causing endemic and emerging toxicity events in Galicia (NW Spain) and Portugal. Results here relating cell numbers to electrochemical signals will be used in an early warning biosensor for toxic algae.


Subject(s)
Biosensing Techniques , Harmful Algal Bloom , Biosensing Techniques/methods , Calibration , Microalgae , Animals , Marine Toxins/analysis , Environmental Monitoring/methods
5.
Harmful Algae ; 138: 102686, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39244229

ABSTRACT

Several Dinophysis species can produce potent lipophilic toxins that pose a risk to human health when contaminated seafood is consumed, especially filter-feeding bivalve mussels. In the mussel farms of the Northwestern Adriatic Sea, seawater and seafood are regularly monitored for the presence of Dinophysis species and their associated toxins, but the current methodological approaches, such as light microscopy determinations, require a long time to make results available to local authorities. A molecular qPCR-based assay can be used to quantify various toxic Dinophysis species in a shorter timeframe. However, this approach is not currently employed in official testing activities. In this study, field samples were collected monthly or bi-weekly over one year from various mussel farms along the Northwestern Adriatic coast. The abundance of Dinophysis species in the seawater was determined using both traditional microscopy and qPCR assays. In addition, the concentration of lipophilic toxins for DSP in mussel flesh was quantified using LC-MS/MS focusing on the okadaic acid group. Dinophysis spp. site-specific single cells were isolated and analysed by qPCR yielding a mean rDNA copy number per cell of 1.21 × 104 ± 1.81 × 103. The qPCR assay gave an efficiency of 98 % and detected up to 10 copies of the rDNA target gene. The qPCR and light microscopy determinations in environmental samples showed a significant positive correlation (Spearman rs = 0.57, p-value < 0.001) with a ratio of 2.24 between the two quantification methods, indicating that light microscopy estimates were generally 44.6 % lower than those obtained by the qPCR assay. The qPCR approach showed several advantages such as rapidity, sensitivity and efficiency over conventional microscopy analysis, showing its potential future role in phytoplankton monitoring under the Official Controls Regulations for shellfish.


Subject(s)
Bivalvia , Dinoflagellida , Animals , Dinoflagellida/genetics , Dinoflagellida/classification , Bivalvia/chemistry , Environmental Monitoring/methods , Marine Toxins/analysis , Seawater/chemistry , Aquaculture
6.
Harmful Algae ; 138: 102701, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39244236

ABSTRACT

Amphidoma languida, a marine thecate dinoflagellate that produces the lipophilic toxin azaspiracids (AZAs), is primarily found in the Atlantic. Although this species has not been recorded in the Asian Pacific, environmental DNAs related to Am. languida have been widely detected in the region by metabarcoding analysis. Their morphology and AZA production remain unclear. In this study, the morphology, ultrastructure, phylogeny, and AZA production of nine Amphidoma strains isolated from Japan, Malaysia, and Philippines were investigated. Phylogenetic trees inferred from rDNAs (SSU, ITS, and LSU rDNA) showed monophyly of the nine Pacific strains and were sister to the Am. languida clade, including the toxigenic strains from the Atlantic. Cells were ellipsoid, 8.7-16.7 µm in length and 7.4-14.0 µm in width, with a conspicuous apical pore complex. A large nucleus in the hyposome, parietal chloroplast with a spherical pyrenoid in the episome, and refractile bodies were observed. Thecal tabulation was typical of Amphidoma, Po, cp, X, 6', 6'', 6C, 5S, 6''', 2''''. A ventral pore was located on the anterior of 1' plate, beside the suture to 6' plate. The presence of a ventral depression, on the anterior of anterior sulcal plate, was different from Am. languida. A large antapical pore, containing approximately 10 small pores, was observed. Cells were apparently smaller than Am. trioculata, a species possessing three pores (ventral pore, ventral depression, and antapical pore). TEM showed the presence of crystalline structures, resembling guanine crystals, and cytoplasmic invaginations into the pyrenoid matrix. Flagellar apparatus lacking the striated root connective is similar to peridinioids and related dinoflagellates. AZAs were not detected from the Pacific strains by LC-MS/MS. This non-toxigenic Amphidoma species, here we propose as Amphidoma fulgens sp. nov., is widely distributed in the Asian Pacific. Moreover, molecular comparison also suggested that most of the environmental DNA sequences previously reported as Am. languida or related sequences from the Asian Pacific were attributable to Am. fulgens.


Subject(s)
Dinoflagellida , Phylogeny , Dinoflagellida/genetics , Dinoflagellida/ultrastructure , Dinoflagellida/classification , Japan , Pacific Ocean , Malaysia , Marine Toxins , Spiro Compounds , DNA, Ribosomal/genetics , Philippines , Polyether Toxins
7.
Harmful Algae ; 138: 102704, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39244239

ABSTRACT

The production of allelochemicals by the toxigenic dinoflagellate Alexandrium catenella is one of the suggested mechanisms to facilitate its bloom formation and persistence by outcompeting other phototrophic protists and reducing grazing pressure. In Southern California, toxic events caused by A. catenella and paralytic shellfish toxins (PSTs) regularly impact coastal ecosystems; however, the trophic interactions and mechanisms promoting this species in a food web context are still not fully understood. In the present study, we combined a dynamical mathematical model with laboratory experiments to investigate potential toxic and allelochemical effects of an A. catenella strain isolated off the coast of Los Angeles, Southern California, on competitors and a common zooplankton consumer. Experiments were conducted using three toxigenic strains of A. catenella, comparing the new Californian isolate (Alex Cal) to two strains previously described from the North Sea, a lytic (Alex2) and non-lytic (Alex5) strain, testing for donor density-dependent effects on two phytoplankton species (Rhodomonas salina, Tetraselmis sp.) and on the rotifer Brachionus plicatilis. Bioassays revealed a steep decline in competitor and consumer populations with increasing Alex Cal concentrations, indicating an intermediate lytic activity compared to the North Sea strains (lytic Alex2 and non-lytic Alex5). The rotifer fed and grew well on the PST- toxic, but non-lytic Alex5 strain, while its survival significantly decreased with increasing concentrations of the two lytic strains Alex Cal and Alex 2, indicating that negative effects on the rotifer were mediated by allelochemicals rather than PST-toxins. Mixed culture experiments including both competitors and consumers demonstrated that the intensity of allelochemical effects not only depended on the A. catenella density but also on the target density. Negative effects on grazers were alleviated by co-occurring competitors with a lower sensitivity to allelochemicals, thus reducing harmful compounds and allowing grazing control on the dinoflagellate to come into effect again. Results from mixed culture experiments were supported by the mathematical approach used in this study which was calibrated with data from simple monoculture growth, pairwise competition and predator-prey experiments, demonstrating the applicability of this model approach to predict the outcome of more complex food web dynamics at the community level.


Subject(s)
Dinoflagellida , Pheromones , Dinoflagellida/physiology , Dinoflagellida/metabolism , Pheromones/metabolism , Animals , Food Chain , California , Marine Toxins/metabolism , Zooplankton/physiology
8.
Int J Mol Sci ; 25(17)2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39273145

ABSTRACT

Marine algal toxins have garnered significant attention in the research community for their unique biochemical properties and potential medical applications. These bioactive compounds, produced by microalgae, pose significant risks due to their high toxicity, yet offer promising therapeutic benefits. Despite extensive research identifying over 300 marine algal toxins, including azaspiracids, brevetoxins, cyclic imines, and yessotoxins, gaps remain in the understanding of their pharmacological potential. In this paper, we critically review the classification, bioactive components, toxicology, pharmacological activities, and mechanisms of these toxins, with a particular focus on their clinical applications. Our motivation stems from the increasing interest in marine algal toxins as candidates for drug development, driven by their high specificity and affinity for various biological receptors. We aim to bridge the gap between toxicological research and therapeutic application, offering insights into the advantages and limitations of these compounds in comparison to other bioactive substances. This review not only enhances the understanding of marine algal toxins' complexity and diversity, but also highlights their extensive application potential in medicine and bioscience, providing a foundation for future research and development in this field.


Subject(s)
Marine Toxins , Marine Toxins/toxicity , Marine Toxins/chemistry , Marine Toxins/pharmacology , Humans , Animals , Oxocins/toxicity , Oxocins/chemistry , Oxocins/pharmacology , Microalgae/chemistry , Polyether Toxins , Mollusk Venoms
9.
Anal Chem ; 96(37): 15050-15058, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39234915

ABSTRACT

An efficient electrochemiluminescence (ECL) emitter, Ir(ppy)3-based molecules has recently been reported to exhibit aggregation-induced electrochemiluminescence (AIECL) phenomenon. However, it remains a significant challenge to control the aggregation states of these molecules and achieve uniform aggregates with intense ECL emission. In this work, a biosensor was developed to detect microcystin-LR (MC-LR) based on Ir(ppy)3-functionalized zeolitic imidazolate framework-8 (Ir-ZIF-8) as the ECL emitter and the trans-cleavage activity of CRISPR-Cas12a as the methodological strategy. The Ir-ZIF-8, a functional metal-organic framework (MOF), exhibited the AIECL phenomenon via the spatial domain-limiting effect of encapsulating Ir(ppy)3 into the mesopores of ZIF-8, while the porosity and highly ordered topological structure of ZIF-8 effectively limited the molecular motion of Ir(ppy)3. CRISPR-Cas12a was employed to indiscriminately cleave double-stranded DNA decorated with carboxy tetramethylrhodamine (TAMRA), which quenched the ECL signal of Ir-ZIF-8 by resonance energy transfer and then separated the quencher from Ir-ZIF-8 to reactivate the signal. The concentration of MC-LR was designed to correlate with both the quencher amount and the activity of Cas12a. Then, two linear regression equations for MC-LR detection were constructed to improve the accuracy of the biosensor, and the constructed biosensor showed remarkable reproducibility, stability, and selectivity. The accurate detection of MC-LR with limits of detection of 1.2 and 5.9 pg/mL was made possible by the high quenching efficiency of TAMRA and the effective cutting ability of the editable CRISPR-Cas12a system.


Subject(s)
Biosensing Techniques , CRISPR-Cas Systems , Electrochemical Techniques , Luminescent Measurements , Marine Toxins , Microcystins , Microcystins/analysis , Microcystins/chemistry , Marine Toxins/chemistry , CRISPR-Cas Systems/genetics , Biosensing Techniques/methods , Zeolites/chemistry , Metal-Organic Frameworks/chemistry , Imidazoles/chemistry , Limit of Detection , CRISPR-Associated Proteins/metabolism , CRISPR-Associated Proteins/chemistry
10.
Cells ; 13(17)2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39273011

ABSTRACT

Microcystin-LR (MC-LR), a cyanobacterial toxin, is a potent carcinogen implicated in colorectal cancer (CRC) progression. However, its impact on the tumor microenvironment (TME) during CRC development remains poorly understood. This study investigates the interaction between tumor cells and macrophages mediated by MC-LR within the TME and its influence on CRC progression. CRC mice exposed to MC-LR demonstrated a significant transformation from adenoma to adenocarcinoma. The infiltration of macrophages increased, and the IRE1α/XBP1 pathway was activated in CRC cells after MC-LR exposure, influencing macrophage M2 polarization under co-culture conditions. Additionally, hexokinase 2 (HK2), a downstream target of the IRE1α/XBP1 pathway, was identified, regulating glycolysis and lactate production. The MC-LR-induced IRE1α/XBP1/HK2 axis enhanced lactate production in CRC cells, promoting M2 macrophage polarization. Furthermore, co-culturing MC-LR-exposed CRC cells with macrophages, along with the IRE1α/XBP1 pathway inhibitor 4µ8C and the hexokinase inhibitor 2-DG, suppressed M2 macrophage-induced CRC cell migration, clonogenicity, and M2 macrophage polarization. This study elucidates the mechanism by which MC-LR-mediated interactions through the IRE1α/XBP1 pathway promote CRC progression, highlighting potential therapeutic targets.


Subject(s)
Colorectal Neoplasms , Endoribonucleases , Macrophages , Microcystins , Signal Transduction , Animals , Humans , Mice , Cell Line, Tumor , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Disease Progression , Endoribonucleases/metabolism , Hexokinase/metabolism , Macrophages/metabolism , Macrophages/drug effects , Marine Toxins , Microcystins/pharmacology , Protein Serine-Threonine Kinases/metabolism , Signal Transduction/drug effects , Tumor Microenvironment/drug effects , X-Box Binding Protein 1/metabolism
11.
Sci Total Environ ; 953: 176039, 2024 Nov 25.
Article in English | MEDLINE | ID: mdl-39241870

ABSTRACT

Domoic acid (DA) is a compound generated as a secondary metabolite during harmful algal blooms, has historically received attention as the potent neurotoxicity in marine environment. However, the aerobic degradation mechanism of DA and the DA-degrader remain largely unknown. Here, we revealed the mechanism of aerobic degradation of DA by a ubiquitous marine Pseudoalteromonas sp., and more importantly, we confirmed that the degradation of DA is mediated by biogenic reactive oxygen species (ROS), rather than direct enzyme-mediated as traditionally conceived. Results indicated that DA degradation was caused by biogenic O2- and OH, where DA underwent reactions of decarboxylation, hydroxylation, and oxidation to yield the detoxification terminal product. Besides, whole genome sequencing and RT-qPCR analysis revealed that the genes conferring to encoding leucine dehydrogenase (ldh) and Na+-translocated NADH-quinone oxidoreductase (nqrA, nqrF) are responsible for biogenic ROS production. Finally, we found through comparative proteomic analysis that biogenic ROS mediated the DA degradation may be prevalent in the environment. Overall, this work not only reveals aerobic biotransformation mechanism of DA, but also identifies a novel mechanism of DA degradation, which provides new perspective into the environmental fate of DA and the artificial bioremediation of DA.


Subject(s)
Kainic Acid , Marine Toxins , Reactive Oxygen Species , Marine Toxins/metabolism , Reactive Oxygen Species/metabolism , Kainic Acid/analogs & derivatives , Kainic Acid/metabolism , Biodegradation, Environmental , Pseudoalteromonas/metabolism , Pseudoalteromonas/genetics , Water Pollutants, Chemical/metabolism
12.
Chemosphere ; 364: 143274, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39243896

ABSTRACT

Addressing the critical health concerns posed by domoic acid (DA), a neurotoxic compound produced by toxic marine algae and bioaccumulated in shellfish, necessitates the development of a rapid, precise, and robust detection system. Traditional DA detection methods have stability and sensitivity issues, which hinder effective toxin detection. To overcome these limitations, we developed a novel direct competitive enzyme-linked immunosorbent assay (dc-ELISA) platform that utilizes peptide-immobilized magnetic beads (MGBs/peptide). The affinity peptides identified through phage display and chemically synthesized with biotin labels present an innovative alternative to conventional antibodies for ELISA applications. Streptavidin-modified MGBs were used as the bioreceptor carriers to facilitate magnetic separation and simplify sample preparation, making the MGB/peptide-based dc-ELISA platform an ideal tool for comprehensive monitoring efforts. The developed platform exhibits a detection range of 0.5-10 ng mL-1 and a low limit of detection of 0.29 ng mL-1, offering enhanced sensitivity and cost-effectiveness. Moreover, our developed dc-ELISA demonstrated a high recovery rate when validated with DA-spiked CRM-mussel samples. This method overcomes the limitations of traditional detection techniques and offers a scalable and efficient approach to marine toxin surveillance with improved marine environmental monitoring and public health management.


Subject(s)
Enzyme-Linked Immunosorbent Assay , Kainic Acid , Marine Toxins , Peptides , Shellfish , Kainic Acid/analogs & derivatives , Kainic Acid/analysis , Enzyme-Linked Immunosorbent Assay/methods , Shellfish/analysis , Peptides/chemistry , Peptides/analysis , Marine Toxins/analysis , Animals , Limit of Detection , Bivalvia/chemistry , Food Contamination/analysis
13.
Environ Geochem Health ; 46(11): 430, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39316189

ABSTRACT

Cyanobacterial toxins are the most common algal toxins, which are highly toxic and can persist in the aquatic environment without easy degradation, posing risks to the ecosystem and human health that cannot be ignored. Although microbiological methods for the removal of cyanobacterial toxins from aqueous environments are highly efficient, their degradation efficiency is susceptible to many abiotic environmental factors. In this paper, Microcystin-LR (MC-LR) and its microbial degrading enzymes were selected to study the effects of common environmental factors (temperature (T), NO3-, NH4+, Cu2+, Zn2+) and their levels during microbial degradation of cyanobacterial toxins in aqueous environments by using molecular docking, molecular dynamics simulation, analytical factor design, and the combined toxicokinetics of TOPKAT (toxicity prediction). It was found that the addition of T, NO3- and Cu2+ to the aqueous environment promoted the microbial degradation of MC-LR, while the addition of NH4+ and Zn2+ inhibited the degradation; The level effect study showed that the microbial degradation of MC-LR was promoted by increasing levels of added T and NO3- in the aqueous environment, whereas it was inhibited and then promoted by increasing levels of NH4+, Cu2+ and Zn2+. In addition, the predicted toxicity of common Microcystins (MCs) showed that MC-LR, Microcystin-RR (MC-RR) and Microcystin-YR (MC-YR) were not carcinogenic, developmentally toxic, mutagenic or ocular irritants in humans. MC-LR and MC-RR are mild skin irritants and MC-YR is not a skin irritant. MC-YR has a higher chronic and acute toxicity in humans than MC-LR and MC-RR. Acute/chronic toxicity intensity for aquatic animals: MC-YR > MC-LR > MC-RR and for aquatic plants: MC-LR > MC-YR > MC-RR. This suggests that MC-YR also has a high environmental health risk. This paper provides theoretical support for optimizing the environmental conditions for microbial degradation of cyanobacterial toxins by studying the effects of common environmental factors and their level effects in the aquatic environment.


Subject(s)
Bacterial Toxins , Marine Toxins , Microcystins , Microcystins/metabolism , Microcystins/toxicity , Microcystins/chemistry , Marine Toxins/metabolism , Marine Toxins/toxicity , Bacterial Toxins/metabolism , Bacterial Toxins/toxicity , Biodegradation, Environmental , Cyanobacteria/metabolism , Cyanobacteria Toxins , Molecular Docking Simulation , Water Pollutants, Chemical/toxicity , Water Pollutants, Chemical/metabolism , Molecular Dynamics Simulation
14.
Toxins (Basel) ; 16(9)2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39330832

ABSTRACT

The systemic toxicity of cyclic peptides produced by cyanobacteria (CCPs) is not yet completely understood. Apart from the most known damages to the liver and kidneys, symptoms of their neurotoxicity have also been reported. Hepatotoxic CCPs, like microcystins, as well as non-hepatotoxic anabaenopeptins and planktopeptins, all exhibit cytotoxic and cytostatic effects on mammalian cells. However, responses of different cell types to CCPs depend on their specific modes of interaction with cell membranes. This study demonstrates that non-hepatotoxic planktopeptin BL1125 and anabaenopeptins B and F, at concentrations up to 10 µM, affect normal and tumor human astrocytes (NHA and U87-GM) in vitro by their almost immediate insertion into the lipid monolayer. Like microcystin-LR (up to 1 µM), they inhibit Ser/Thr phosphatases and reorganize cytoskeletal elements, with modest effects on their gene expression. Based on the observed effects on intermediate filaments and intermediate filament linkage elements, their direct or indirect influence on tubulin cytoskeletons via post-translational modifications, we conclude that the basic mechanism of CCP toxicities is the induction of inter- and intracellular communication failure. The assessed inhibitory activity on Ser/Thr phosphatases is also crucial since the signal transduction cascades are modulated by phosphorylation/dephosphorylation processes.


Subject(s)
Astrocytes , Cyanobacteria , Cytoskeleton , Peptides, Cyclic , Humans , Astrocytes/drug effects , Astrocytes/metabolism , Peptides, Cyclic/toxicity , Cytoskeleton/drug effects , Cyanobacteria Toxins , Microcystins/toxicity , Marine Toxins/toxicity , Bacterial Toxins/toxicity , Cell Line, Tumor
15.
Toxins (Basel) ; 16(9)2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39330839

ABSTRACT

When humans consume seafood contaminated by lipophilic polyether phycotoxins, such as azaspiracids (AZAs), the toxins are mainly leached and absorbed in the small intestine, potentially causing intestinal damage. In this study, human intestinal epithelial Caco-2 cells were used to investigate the adverse effects of azaspiracid-2 (AZA-2) on human intestinal epithelial cells. Cell viability, apoptosis, oxidative damage and mitochondrial ultrastructure were investigated, and ribonucleic acid sequence (RNA-seq) analysis was applied to explore the potential mechanisms of AZA-2 toxicity to Caco-2 cells. Results showed that AZA-2 significantly reduced the proliferation of Caco-2 cells in a concentration-dependent response, and the 48 h EC50 of AZA-2 was 12.65 nmol L-1. AZA-2 can induce apoptosis in Caco-2 cells in a dose-dependent manner. Visible mitochondrial swelling, cristae disintegration, membrane rupture and autophagy were observed in Caco-2 cells exposed to AZA-2. Reactive oxygen species (ROS) and malondialdehyde (MDA) content were significantly increased in Caco-2 cells after 48 h of exposure to 1 and 10 nmol L-1 of AZA-2. Transcriptome analysis showed that KEGG pathways related to cellular oxidative damage and lipid metabolism were affected, mainly including mitophagy, oxidative phosphorylation, cholesterol metabolism, vitamin digestion and absorption, bile secretion and the peroxisome proliferator-activated receptor signaling pathway. The cytotoxic effects of AZA-2 on Caco-2 cells may be associated with ROS-mediated autophagy and apoptosis in mitochondrial cells. Results of this study improve understanding of the cytotoxicity and molecular mechanisms of AZA-2 on Caco-2 cells, which is significant for protecting human health.


Subject(s)
Apoptosis , Intestinal Mucosa , Marine Toxins , Oxidative Stress , Spiro Compounds , Humans , Caco-2 Cells , Oxidative Stress/drug effects , Apoptosis/drug effects , Marine Toxins/toxicity , Spiro Compounds/toxicity , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Reactive Oxygen Species/metabolism , Cell Survival/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Polyether Toxins , Furans , Pyrans
16.
Toxins (Basel) ; 16(9)2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39330836

ABSTRACT

Cyanobacteria are cosmopolitan organisms; nonetheless, climate change and eutrophication are increasing the occurrence of cyanobacteria blooms (cyanoblooms), thereby raising the risk of cyanotoxins in water sources used for drinking, agriculture, and livestock. This study aimed to determine the presence of cyanobacteria, including toxigenic cyanobacteria and the occurrence of cyanotoxins in the El Pañe reservoir located in the high-Andean region, Arequipa, Peru, to support water quality management. The study included morphological observation of cyanobacteria, molecular determination of cyanobacteria (16S rRNA analysis), and analysis of cyanotoxins encoding genes (mcyA for microcystins, cyrJ for cylindrospermopsins, sxtl for saxitoxins, and AnaC for anatoxins). In parallel, chemical analysis using Liquid Chromatography coupled with Mass Spectrometry (LC-MS/MS) was performed to detect the presence of cyanotoxins (microcystins, cylindrospermopsin, saxitoxin, and anatoxin, among others) and quantification of Microcystin-LR. Morphological data show the presence of Dolichospermum sp., which was confirmed by molecular analysis. Microcystis sp. was also detected through 16S rRNA analysis and the presence of mcyA gene related to microcystin production was found in both cyanobacteria. Furthermore, microcystin-LR and demethylated microcystin-LR were identified by chemical analysis. The highest concentrations of microcystin-LR were 40.60 and 25.18 µg/L, in May and November 2022, respectively. Microcystins were detected in cyanobacteria biomass. In contrast, toxins in water (dissolved) were not detected. Microcystin concentrations exceeded many times the values established in Peruvian regulation and the World Health Organization (WHO) in water intended for human consumption (1 µg/L). This first comprehensive report integrates morphological, molecular, and chemical data and confirms the presence of two toxigenic cyanobacteria and the presence of microcystins in El Pañe reservoir. This work points out the need to implement continuous monitoring of cyanobacteria and cyanotoxins in the reservoir and effective water management measures to protect the human population from exposure to these contaminants.


Subject(s)
Bacterial Toxins , Cyanobacteria , Environmental Monitoring , Microcystins , Peru , Cyanobacteria/genetics , Cyanobacteria/metabolism , Bacterial Toxins/analysis , Bacterial Toxins/genetics , Microcystins/analysis , Water Quality , Cyanobacteria Toxins , Water Microbiology , Marine Toxins/analysis
17.
Toxins (Basel) ; 16(9)2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39330859

ABSTRACT

Microcystin-LR (MC-LR), frequently generated by cyanobacteria, has been demonstrated to raise the likelihood of liver disease. Few previous studies have explored the potential antagonist against MC-LR. Astaxanthin (ASX) has been shown to possess various beneficial effects in regulating lipid metabolism in the liver. However, whether ASX could alleviate MC-LR-induced hepatic lipid metabolic dysregulation is as yet unclear. In this work, the important roles and mechanisms of ASX in countering MC-LR-induced liver damage and lipid metabolic dysregulation were explored for the first time. The findings revealed that ASX not only prevented weight loss but also enhanced liver health after MC-LR exposure. Moreover, ASX effectively decreased triglyceride, total cholesterol, aspartate transaminase, and alanine aminotransferase contents in mice that were elevated by MC-LR. Histological observation showed that ASX significantly alleviated lipid accumulation and inflammation induced by MC-LR. Mechanically, ASX could significantly diminish the expression of genes responsible for lipid generation (Srebp-1c, Fasn, Cd36, Scd1, Dgat1, and Pparg), which probably reduced lipid accumulation induced by MC-LR. Analogously, MC-LR increased intracellular lipid deposition in THLE-3 cells, while ASX decreased these symptoms by down-regulating the expression of key genes in the lipid synthesis pathway. Our results implied that ASX played a crucial part in lipid synthesis and effectively alleviated MC-LR-induced lipid metabolism dysregulation. ASX might be developed as a novel protectant against hepatic impairment and lipid metabolic dysregulation associated with MC-LR. This study offers new insights for further management of MC-LR-related metabolic diseases.


Subject(s)
Lipid Metabolism , Liver , Marine Toxins , Microcystins , Xanthophylls , Microcystins/toxicity , Animals , Xanthophylls/pharmacology , Lipid Metabolism/drug effects , Liver/drug effects , Liver/metabolism , Liver/pathology , Mice , Male , Mice, Inbred C57BL , Cell Line , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/prevention & control
19.
Ecotoxicol Environ Saf ; 284: 116990, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39236658

ABSTRACT

Marine toxins pose a significant safety risk, leading to human intoxications and causing substantial economic losses in seafood-producing regions. The development of rapid, cost-effective, efficient, and reliable approaches for the containment of these substances is therefore crucial in order to mitigate the adverse impact of marine toxins. This research conducted a comprehensive review on the toxicity and influencing factors of marine toxins production. Additionally, depuration technologies, including adsorption, advanced oxidation processes, biodegradation, heating treatment, temporary maintenance and purification, and drug inhibition, were systematically summarized. The study also provided a comparative analysis of the advantages and disadvantages of various depuration technologies and proposed strategies for future development.


Subject(s)
Marine Toxins , Marine Toxins/toxicity , Water Pollutants, Chemical/toxicity , Animals , Environmental Monitoring/methods , Biodegradation, Environmental , Adsorption , Humans , Aquatic Organisms/drug effects
20.
Toxins (Basel) ; 16(8)2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39195738

ABSTRACT

Peracetic acid (PAA) shows potential for use in drinking water treatment as an alternative to prechlorination, such as for mussel control and disinfection by-product precursor destruction, though its impact as a preoxidant during cyanobacterial blooms remains underexplored. Here, Microcystis aeruginosa inactivation and microcystin-LR and -RR release and degradation using PAA were explored. The toxin degradation rates were found to be higher in alkaline conditions than in neutral and acidic conditions. However, all rates were significantly smaller than comparable rates when using free chlorine. The inactivation of M. aeruginosa cells using PAA was faster at acidic pH, showing immediate cell damage and subsequent cell death after 15-60 min of exposure to 10 mg/L PAA. In neutral and alkaline conditions, cell death occurred after a longer lag phase (3-6 h). During cell inactivation, microcystin-LR was released slowly, with <35% of the initial intracellular toxins measured in solution after 12 h of exposure to 10 mg/L PAA. Overall, PAA appears impractically slow for M. aeruginosa cell inactivation or microcystin-LR and -RR destruction in drinking water treatment, but this slow reactivity may also allow it to continue to be applied as a preoxidant for other purposes during cyanobacterial blooms without the risk of toxin release.


Subject(s)
Marine Toxins , Microcystins , Microcystis , Oxidation-Reduction , Peracetic Acid , Microcystis/drug effects , Microcystis/metabolism , Microcystins/toxicity , Microcystins/metabolism , Peracetic Acid/pharmacology , Marine Toxins/toxicity , Water Purification/methods , Hydrogen-Ion Concentration , Drinking Water/microbiology , Drinking Water/chemistry
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