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Toxicological Challenges of Aquatic Toxins
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Toxicological Challenges of Aquatic Toxins

A topical collection in Toxins (ISSN 2072-6651). This collection belongs to the section "Marine and Freshwater Toxins".

Viewed by 77994

Editor

Prof. Dr. Luis M. Botana

E-Mail Website
Collection Editor
Department of Pharmacology, Veterinary School, University Santiago de Compostela, Campus Lugo, 27002 Lugo, Spain
Interests: marine and freshwater detection; toxicology; pharmacology
Special Issues, Collections and Topics in MDPI journals

Topical Collection Information

Dear Colleagues,

Although marine and freshwater toxins are being explored by many research groups worldwide, they are still largely unknown. There is no sound explanation to justify the reason to their production by microalgae or cyanobacteria. In addition, their modes of action are, in several cases, unknown, and, in very few cases, the toxicity symptoms are ascribed to a defined molecular target. Some old toxin groups require a revision of the so-far-accepted mechanism of toxicity (i.e., phosphatase inhibitors), and this extends, especially in the case of marine toxins, to the interpretation of their toxicity equivalency factors, which are legally very important for monitoring and international trading. Additionally, knowledge of their pharmacokinetics is very limited, and in some cases even the concept of a compound being (or not) a toxin itself requires further research (i.e., cyclic imines or yessotoxin). 

This topical collection will provide room for articles dealing with these gaps.

Prof. Dr. Luis M. Botana
Guest Editor

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Keywords

  • Marine toxin
  • Cyanotoxin
  • Mechanism of action
  • Toxicity
  • Toxicity equivalency factor
  • Pharmacological interaction
  • Microalgae production

Published Papers (16 papers)

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2023

Jump to: 2020, 2019

12 pages, 1540 KiB  
Article
Okadaic Acid Is at Least as Toxic as Dinophysistoxin-1 after Repeated Administration to Mice by Gavage
by Se Yong Park, Ju-Hee Kang, Hyun Jin Jung, Jung Ho Hwang, Hyang Sook Chun, Yeo Sung Yoon and Seung Hyun Oh
Toxins 2023, 15(10), 587; https://doi.org/10.3390/toxins15100587 - 23 Sep 2023
Cited by 1 | Viewed by 1124
Abstract
Okadaic acid (OA) and its analogues cause diarrhetic shellfish poisoning (DSP) in humans, and risk assessments of these toxins require toxicity equivalency factors (TEFs), which represent the relative toxicities of analogues. However, no human death by DSP toxin has been reported, and its [...] Read more.
Okadaic acid (OA) and its analogues cause diarrhetic shellfish poisoning (DSP) in humans, and risk assessments of these toxins require toxicity equivalency factors (TEFs), which represent the relative toxicities of analogues. However, no human death by DSP toxin has been reported, and its current TEF value is based on acute lethality. To properly reflect the symptoms of DSP, such as diarrhea without death, the chronic toxicity of DSP toxins at sublethal doses should be considered. In this study, we obtained acute oral LD50 values for OA and dinophysistoxin-1 (DTX-1) (1069 and 897 μg/kg, respectively) to set sublethal doses. Mice were treated with sublethal doses of OA and DTX-1 for 7 days. The mice lost body weight, and the disease activity index and intestinal crypt depths increased. Furthermore, these changes were more severe in OA-treated mice than in the DTX-1-treated mice. Strikingly, ascites was observed, and its severity was greater in mice treated with OA. Our findings suggest that OA is at least as toxic as DTX-1 after repeated oral administration at a low dose. This is the first study to compare repeated oral dosing of DSP toxins. Further sub-chronic and chronic studies are warranted to determine appropriate TEF values for DSP toxins. Full article
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2020

Jump to: 2023, 2019

19 pages, 7380 KiB  
Article
In Vivo Evaluation of the Chronic Oral Toxicity of the Marine Toxin Palytoxin
by Andrea Boente-Juncal, Sandra Raposo-García, Carmen Vale, M. Carmen Louzao, Paz Otero and Luis M. Botana
Toxins 2020, 12(8), 489; https://doi.org/10.3390/toxins12080489 - 30 Jul 2020
Cited by 9 | Viewed by 3530
Abstract
Palytoxin (PLTX) is one of the most poisonous substances known to date and considered as an emergent toxin in Europe. Palytoxin binds to the Na+-K+ ATPase, converting the enzyme in a permeant cation channel. This toxin is known for causing [...] Read more.
Palytoxin (PLTX) is one of the most poisonous substances known to date and considered as an emergent toxin in Europe. Palytoxin binds to the Na+-K+ ATPase, converting the enzyme in a permeant cation channel. This toxin is known for causing human fatal intoxications associated with the consumption of contaminated fish and crustaceans such as crabs, groupers, mackerel, and parrotfish. Human intoxications by PLTX after consumption of contaminated fishery products are a serious health issue and can be fatal. Different reports have previously explored the acute oral toxicity of PLTX in mice. Although the presence of palytoxin in marine products is currently not regulated in Europe, the European Food Safety Authority expressed its opinion on PLTX and demanded assessment for chronic toxicity studies of this potent marine toxin. In this study, the chronic toxicity of palytoxin was evaluated after oral administration to mice by gavage during a 28-day period. After chronic exposure of mice to the toxin, a lethal dose 50 (LD50) of 0.44 µg/kg of PLTX and a No-Observed-Adverse-Effect Level (NOAEL) of 0.03 µg/kg for repeated daily oral administration of PLTX were determined. These results indicate a much higher chronic toxicity of PLTX and a lower NOAEL than that previously described in shorter treatment periods, pointing out the need to further reevaluate the levels of this compound in marine products. Full article
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2019

Jump to: 2023, 2020

13 pages, 2359 KiB  
Article
Cloning and Expression of Genes for Biodegrading Nodularin by Sphingopyxis sp. USTB-05
by Qianqian Xu, Hongfei Ma, Jinhui Fan, Hai Yan, Haiyang Zhang, Chunhua Yin, Xiaolu Liu, Yang Liu and Huasheng Wang
Toxins 2019, 11(10), 549; https://doi.org/10.3390/toxins11100549 - 20 Sep 2019
Cited by 10 | Viewed by 2717
Abstract
Biodegradation is efficient for removing cyanobacterial toxins, such as microcystins (MCs) and nodularin (NOD). However, not all the microbial strains with the microcystin-biodegrading enzymes MlrA and MlrC could biodegrade NOD. Studies on genes and enzymes for biodegrading NOD can reveal the function and [...] Read more.
Biodegradation is efficient for removing cyanobacterial toxins, such as microcystins (MCs) and nodularin (NOD). However, not all the microbial strains with the microcystin-biodegrading enzymes MlrA and MlrC could biodegrade NOD. Studies on genes and enzymes for biodegrading NOD can reveal the function and the biodegradation pathway of NOD. Based on successful cloning and expression of the USTB-05-A and USTB-05-C genes from Sphingopyxis sp. USTB-05, which are responsible for the biodegradation of MCs, the pathway for biodegrading NOD by these two enzymes was investigated in this study. The findings showed that the enzyme USTB-05-A converted cyclic NOD (m/z 825.4516) into its linear type as the first product by hydrolyzing the arginine and Adda peptide bond, and that USTB-05-C cut off the Adda and glutamic acid peptide bond of linearized NOD (m/z 843.4616) and produced dimeric Adda (m/z 663.4377) as the second product. Further, based on the homology modeling of enzyme USTB-05-A, site-directed mutants of USTB-05-A were constructed and seven crucial sites for enzyme USTB-05-A activity were found. A complete enzymatic mechanism for NOD biodegradation by USTB-05-A in the first step was proposed: glutamic acid 172 and histidine 205 activate a water molecule facilitating a nucleophilic attack on the arginine and Adda peptide bond of NOD; tryptophan 176 and tryptophan 201 contact the carboxylate side chain of glutamic acid 172 and accelerate the reaction rates; and histidine 260 and asparagine 264 function as an oxyanion hole to stabilize the transition states. Full article
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13 pages, 12341 KiB  
Article
Prodigiosin Promotes Nrf2 Activation to Inhibit Oxidative Stress Induced by Microcystin-LR in HepG2 Cells
by Jihua Chen, Yuji Li, Fuqiang Liu, De-Xing Hou, Jingjing Xu, Xinying Zhao, Fei Yang and Xiangling Feng
Toxins 2019, 11(7), 403; https://doi.org/10.3390/toxins11070403 - 12 Jul 2019
Cited by 25 | Viewed by 4003
Abstract
Microcystin-LR (MC-LR), a cyanotoxin produced by cyanobacteria, induces oxidative stress in various types of cells. Prodigiosin, a red linear tripyrrole pigment, has been recently reported to have antimicrobial, antioxidative, and anticancer properties. How prodigiosin reacts to reactive oxygen species (ROS) induced by MC-LR [...] Read more.
Microcystin-LR (MC-LR), a cyanotoxin produced by cyanobacteria, induces oxidative stress in various types of cells. Prodigiosin, a red linear tripyrrole pigment, has been recently reported to have antimicrobial, antioxidative, and anticancer properties. How prodigiosin reacts to reactive oxygen species (ROS) induced by MC-LR is still undetermined. This study aimed to examine the effect of prodigiosin against oxidative stress induced by MC-LR in HepG2 cells. Ros was generated after cells were treated with MC-LR and was significantly inhibited with treatment of prodigiosin. In prodigiosin-treated cells, the levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2-related phase II enzyme heme oxygenase-1 (HO-1) were increased. Besides, prodigiosin contributed to enhance nuclear Nrf2 level and repressed ubiquitination. Furthermore, prodigiosin promoted Nrf2 protein level and inhibited ROS in Nrf2 knocked down HepG2 cells. Results indicated that prodigiosin reduced ROS induced by MC-LR by enhancing Nrf2 translocation into the nucleus in HepG2 cells. The finding presents new clues for the potential clinical applications of prodigiosin for inhibiting MC-LR-induced oxidative injury in the future. Full article
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16 pages, 1891 KiB  
Article
LC–MS/MS Analysis of the Emerging Toxin Pinnatoxin-G and High Levels of Esterified OA Group Toxins in Galician Commercial Mussels
by Paz Otero, Natalia Miguéns, Inés Rodríguez and Luis M. Botana
Toxins 2019, 11(7), 394; https://doi.org/10.3390/toxins11070394 - 05 Jul 2019
Cited by 29 | Viewed by 3934
Abstract
The occurrence of marine harmful algae is increasing worldwide and, therefore, the accumulation of lipophilic marine toxins from harmful phytoplankton represents a food safety threat in the shellfish industry. Galicia, which is a commercially important EU producer of edible bivalve mollusk have been [...] Read more.
The occurrence of marine harmful algae is increasing worldwide and, therefore, the accumulation of lipophilic marine toxins from harmful phytoplankton represents a food safety threat in the shellfish industry. Galicia, which is a commercially important EU producer of edible bivalve mollusk have been subjected to recurring cases of mussel farm closures, in the last decades. This work aimed to study the toxic profile of commercial mussels (Mytilus galloprovincialis) in order to establish a potential risk when ingested. For this, a total of 41 samples of mussels farmed in 3 Rías (Ares-Sada, Arousa, and Pontevedra) and purchased in 5 local markets were analyzed by liquid chromatography tandem mass spectrometry (LC–MS/MS). Chromatograms showed the presence of okadaic acid (OA), dinophysistoxin-2 (DTX-2), pectenotoxin-2 (PTX-2), azaspiracid-2 (AZA-2), and the emerging toxins 13-desmethyl spirolide C (SPX-13), and pinnatoxin-G (PnTX-G). Quantification of each toxin was determined using their own standard calibration in the range 0.1%–50 ng/mL (R2 > 0.99) and by considering the toxin recovery (62–110%) and the matrix correction (33–211%). Data showed that OA and DTX-2 (especially in the form of esters) are the main risk in Galician mollusks, which was detected in 38 samples (93%) and 3 of them exceeded the legal limit (160 µg/kg), followed by SPX-13 that was detected in 19 samples (46%) in quantities of up to 28.9 µg/kg. Analysis from PTX-2, AZA-2, and PnTX-G showed smaller amounts. Fifteen samples (37%) were positive for PTX-2 (0.7–2.9 µg/kg), 12 samples (29%) for AZA-2 (0.1–1.8 µg/kg), and PnTX-G was detected in 5 mussel samples (12%) (0.4 µg/kg–0.9 µg/kg). This is the first time Galician mollusk was contaminated with PnTX-G. Despite results indicating that this toxin was not a potential risk through the mussel ingestion, it should be considered in the shellfish safety monitoring programs through the LC–MS/MS methods. Full article
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13 pages, 2318 KiB  
Article
The Efficiency of Microstrainers Filtration in the Process of Removing Phytoplankton with Special Consideration of Cyanobacteria
by Wanda Czyżewska and Marlena Piontek
Toxins 2019, 11(5), 285; https://doi.org/10.3390/toxins11050285 - 21 May 2019
Cited by 12 | Viewed by 3582
Abstract
The research presented in this manuscript concerns the evaluation of the effectiveness of microstrainers, which are designed to reduce the amount of plankton in treated surface water. The efficiency of microstrainer filtration analysis is very important for the proper course of the water-treatment [...] Read more.
The research presented in this manuscript concerns the evaluation of the effectiveness of microstrainers, which are designed to reduce the amount of plankton in treated surface water. The efficiency of microstrainer filtration analysis is very important for the proper course of the water-treatment process not only in the Water-Treatment Plant (WTP) in Zielona Góra (central western Poland) but also in other WTPs around the world. The qualitative and quantitative monitoring of the abundance of plankton including cyanobacteria during the particle-filtration process allows not only for the assessment of the potential cyanotoxic risk in surface water providing a source of drinking water, but also allows the evaluation of the action and the prevention of adverse impacts of microstrainers. Over four years of research, it was observed that the largest amount of cyanobacteria before microstrainer filtration took place in May. The dominant species was Limnothrix redeckei. The microstrainer removal of plankton and cyanobacteria was statistically significant. The quantity of removed plankton increased with its increasing content in raw water. The particle-filtration process, by reducing the amount of cyanobacteria, contributes to a decrease in intracellular microcystins. Full article
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14 pages, 1810 KiB  
Article
Using Advanced Spectroscopy and Organic Matter Characterization to Evaluate the Impact of Oxidation on Cyanobacteria
by Saber Moradinejad, Caitlin M. Glover, Jacinthe Mailly, Tahere Zadfathollah Seighalani, Sigrid Peldszus, Benoit Barbeau, Sarah Dorner, Michèle Prévost and Arash Zamyadi
Toxins 2019, 11(5), 278; https://doi.org/10.3390/toxins11050278 - 17 May 2019
Cited by 9 | Viewed by 3714
Abstract
Drinking water treatment plants throughout the world are increasingly facing the presence of toxic cyanobacteria in their source waters. During treatment, the oxidation of cyanobacteria changes cell morphology and can potentially lyse cells, releasing intracellular metabolites. In this study, a combination of techniques [...] Read more.
Drinking water treatment plants throughout the world are increasingly facing the presence of toxic cyanobacteria in their source waters. During treatment, the oxidation of cyanobacteria changes cell morphology and can potentially lyse cells, releasing intracellular metabolites. In this study, a combination of techniques was applied to better understand the effect of oxidation with chlorine, ozone, potassium permanganate, and hydrogen peroxide on two cell cultures (Microcystis, Dolichospermum) in Lake Champlain water. The discrepancy observed between flow cytometry cell viability and cell count numbers was more pronounced for hydrogen peroxide and potassium permanganate than ozone and chlorine. Liquid chromatography with organic carbon and nitrogen detection was applied to monitor the changes in dissolved organic matter fractions following oxidation. Increases in the biopolymer fraction after oxidation with chlorine and ozone were attributed to the release of intracellular algal organic matter and/or fragmentation of the cell membrane. A novel technique, Enhanced Darkfield Microscopy with Hyperspectral Imaging, was applied to chlorinated and ozonated samples. Significant changes in the peak maxima and number of peaks were observed for the cell walls post-oxidation, but this effect was muted for the cell-bound material, which remained relatively unaltered. Full article
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12 pages, 2797 KiB  
Article
Isolation of a Novel Microcystin-Degrading Bacterium and the Evolutionary Origin of mlr Gene Cluster
by Lian Qin, Xiaoxing Zhang, Xiaoguo Chen, Ke Wang, Yitian Shen and Dan Li
Toxins 2019, 11(5), 269; https://doi.org/10.3390/toxins11050269 - 13 May 2019
Cited by 15 | Viewed by 3263
Abstract
The mlr-dependent biodegradation plays an essential role in the natural attenuation of microcystins (MCs) in eutrophic freshwater ecosystems. However, their evolutionary origin is still unclear due to the lack of mlr gene cluster sequences. In this study, a Sphingopyxis sp. strain X20 [...] Read more.
The mlr-dependent biodegradation plays an essential role in the natural attenuation of microcystins (MCs) in eutrophic freshwater ecosystems. However, their evolutionary origin is still unclear due to the lack of mlr gene cluster sequences. In this study, a Sphingopyxis sp. strain X20 with high MC-degrading ability was isolated, and the mlrA gene activity was verified by heterologous expression. The whole sequence of the mlr gene cluster in strain X20 was obtained through PCR and thermal asymmetric interlaced (TAIL)-PCR, and then used for evolutionary origin analyses together with the sequences available in GenBank. Phylogenetic analyses of mlr gene clusters suggested that the four mlr genes had the same origin and evolutionary history. Genomic island analyses showed that there is a genomic island on the genome of sphingomonads that is capable of degrading MCs, on which the mlr gene cluster anchors. The concentrated distribution of the mlr gene cluster in sphingomonads implied that these genes have likely been present in the sphingomonads gene pool for a considerable time. Therefore, the mlr gene cluster may have initially entered into the genome of sphingomonads together with the genomic island by a horizontal gene transfer event, and then become inherited by some sphingomonads. The species other than sphingomonads have likely acquired mlr genes from sphingomonads by recently horizontal gene transfer due to the sporadic distribution of MC-degrading species and the mlr genes in them. Our results shed new light on the evolutionary origin of the mlr cluster and thus facilitate the interpretation of characteristic distribution of the mlr gene in bacteria and the understanding of whole mlr pathway. Full article
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12 pages, 2364 KiB  
Article
The Ecological Importance of Toxicity: Sea Anemones Maintain Toxic Defence When Bleached
by Cassie M. Hoepner, Catherine A. Abbott and Karen Burke da Silva
Toxins 2019, 11(5), 266; https://doi.org/10.3390/toxins11050266 - 11 May 2019
Cited by 15 | Viewed by 8458
Abstract
Cnidarians are amongst the most venomous animals on the planet. They are also under significant threat due to the impacts of climate change. Corals and anemones undergo climate-induced bleaching during extreme environmental conditions, where a loss of symbiotic photosynthetic algae (zooxanthellae) causes whitening [...] Read more.
Cnidarians are amongst the most venomous animals on the planet. They are also under significant threat due to the impacts of climate change. Corals and anemones undergo climate-induced bleaching during extreme environmental conditions, where a loss of symbiotic photosynthetic algae (zooxanthellae) causes whitening in colour, loss of internal food supply, and reduction in health, which can ultimately lead to death. What has yet to be determined is whether bleaching causes a reduction in the production or quality of venom. In this study, the sea anemone Entacmaea quadricolor was exposed to long-term light-induced bleaching to examine the effect that bleaching has on venom. Venom quality and quantity, as determined through lethality and haemolysis measures and nematocyst production was highly preserved over the five-month imposed bleaching event. Maintenance of venom and nematocyst production, despite a loss of an internal food source provided by endosymbiotic algae, indicates both the ecological importance of maintaining toxicity and a remarkable resilience that anemones have to major environmental stressors. Full article
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18 pages, 3820 KiB  
Article
Toxicity of Cyanopeptides from Two Microcystis Strains on Larval Development of Astyanax altiparanae
by Kelly Fernandes, Andreia Gomes, Leonardo Calado, George Yasui, Diego Assis, Theodore Henry, Ana Fonseca and Ernani Pinto
Toxins 2019, 11(4), 220; https://doi.org/10.3390/toxins11040220 - 13 Apr 2019
Cited by 22 | Viewed by 4328
Abstract
Absorption and accumulation of bioavailable cyanobacterial metabolites (including cyanotoxins) are likely in fish after senescence and the rupturing of cells during bloom episodes. We determined the toxicity of cyanopeptides identified from two strains of Microcystis (M. panniformis MIRS-04 and M. aeruginosa NPDC-01) [...] Read more.
Absorption and accumulation of bioavailable cyanobacterial metabolites (including cyanotoxins) are likely in fish after senescence and the rupturing of cells during bloom episodes. We determined the toxicity of cyanopeptides identified from two strains of Microcystis (M. panniformis MIRS-04 and M. aeruginosa NPDC-01) in a freshwater tropical fish, Astyanax altiparanae (yellowtail tetra, lambari). Aqueous extracts of both Microcystis strains were prepared in order to simulate realistic fish exposure to these substances in a freshwater environment. Both strains were selected because previous assays evidenced the presence of microcystins (MCs) in MIRS-04 and lack of cyanotoxins in NPDC-01. Identification of cyanobacterial secondary metabolites was performed by LC-HR-QTOF-MS and quantification of the MC-LR was carried out by LC-QqQ-MS/MS. MIRS-04 produces the MCs MC-LR, MC-LY and MC-HilR as well as micropeptins B, 973, 959 and k139. NPCD-01 biosynthetizes microginins FR1, FR2/FR4 and SD-755, but does not produce MCs. Larval fish survival and changes in morphology were assessed for 96 h exposure to aqueous extracts of both strains at environmentally relevant concentrations from 0.1 to 0.5 mg (dry weight)/mL, corresponding to 0.15 to 0.74 μg/mL of MC-LR (considering dried amounts of MIRS-04 for comparison). Fish mortality increased with concentration and time of exposure for both strains of Microcystis. The frequencies of morphological abnormalities increased with concentration in both strains, and included abdominal and pericardial oedema, and spinal curvature. Results demonstrate that toxicity was not solely caused by MCs, other classes of cyanobacterial secondary metabolites contributed to the observed toxicity. Full article
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13 pages, 2152 KiB  
Article
15N Stable Isotope Labeling PSTs in Alexandrium minutum for Application of PSTs as Biomarker
by Wancui Xie, Min Li, Lin Song, Rui Zhang, Xiaoqun Hu, Chengzhu Liang and Xihong Yang
Toxins 2019, 11(4), 211; https://doi.org/10.3390/toxins11040211 - 08 Apr 2019
Cited by 1 | Viewed by 3204
Abstract
The dinoflagellate Alexandrium minutum (A. minutum) which can produce paralytic shellfish toxins (PSTs) is often used as a model to study the migration, biotransformation, accumulation, and removal of PSTs. However, the mechanism is still unclear. To provide a new tool for [...] Read more.
The dinoflagellate Alexandrium minutum (A. minutum) which can produce paralytic shellfish toxins (PSTs) is often used as a model to study the migration, biotransformation, accumulation, and removal of PSTs. However, the mechanism is still unclear. To provide a new tool for related studies, we tried to label PSTs metabolically with 15N stable isotope to obtain 15N-PSTs instead of original 14N, which could be treated as biomarker on PSTs metabolism. We then cultured the A. minutum AGY-H46 which produces toxins GTX1-4 in f/2 medium of different 15N/P concentrations. The 15N-PSTs’ toxicity and toxin profile were detected. Meanwhile, the 15N labeling abundance and 15N atom number of 15N-PSTs were identified. The 14N of PSTs produced by A. minutum can be successfully replaced by 15N, and the f/2 medium of standard 15N/P concentration was the best choice in terms of the species’ growth, PST profile, 15N labeling result and experiment cost. After many (>15) generations, the 15N abundance in PSTs extract reached 82.36%, and the 15N atom number introduced into GTX1-4 might be 4–6. This paper innovatively provided the initial evidence that 15N isotope application of labeling PSTs in A. minutum is feasible. The 15N-PSTs as biomarker can be applied and provide further information on PSTs metabolism. Full article
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8 pages, 1724 KiB  
Article
Regulation of Microcystin-LR-Induced DNA Damage by miR-451a in HL7702 Cells
by Lv Chen, Shu Yang, Cong Wen, Shuilin Zheng, Yue Yang, Xiangling Feng, Jihua Chen, Dan Luo, Ran Liu and Fei Yang
Toxins 2019, 11(3), 164; https://doi.org/10.3390/toxins11030164 - 15 Mar 2019
Cited by 23 | Viewed by 3234
Abstract
Microcystin-LR is a cyclic heptapeptide hepatotoxin produced by harmful cyanobacteria. A panel of microRNAs containing miR-451a were found to be significantly changed in normal human liver cells HL7702 after exposure to microcystin-LR (MC-LR) in our previous study. However, the functions of miR-451a in [...] Read more.
Microcystin-LR is a cyclic heptapeptide hepatotoxin produced by harmful cyanobacteria. A panel of microRNAs containing miR-451a were found to be significantly changed in normal human liver cells HL7702 after exposure to microcystin-LR (MC-LR) in our previous study. However, the functions of miR-451a in hepatotoxicity induced by MC-LR remained unclear. The study aimed to investigate the impacts of miR-451a in HL7702 cells following treatment with 5 or 10 μM MC-LR. The comet assay indicated that MC-LR can influence Olive tail moment (OTM) in HL7702 cells. Furthermore, increase of miR-451a significantly repressed DNA damage and the protein expression level of γ-H2AX induced by MC-LR. Moreover, over-expression of miR-451a inhibited the expression level of p-AKT1 protein in cells following treatment by MC-LR. These results showed that miR-451a may protect from MC-LR-induced DNA damage by down-regulating the expression of p-AKT1, which provides new clues for the diagnosis and therapy policies for liver damage induced by MC-LR. Full article
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12 pages, 1462 KiB  
Article
Inhibitory Effect of Metalloproteinase Inhibitors on Skin Cell Inflammation Induced by Jellyfish Nemopilema nomurai Nematocyst Venom
by Aoyu Li, Huahua Yu, Rongfeng Li, Song Liu, Ronge Xing and Pengcheng Li
Toxins 2019, 11(3), 156; https://doi.org/10.3390/toxins11030156 - 10 Mar 2019
Cited by 15 | Viewed by 3710
Abstract
Jellyfish envenomations result in extensive dermatological symptoms, clinically named as jellyfish dermatitis, which can seriously affect the daily activities and physical health of people. Inflammatory response accompanies the whole process of jellyfish dermatitis and the complexity of jellyfish venom components makes it difficult [...] Read more.
Jellyfish envenomations result in extensive dermatological symptoms, clinically named as jellyfish dermatitis, which can seriously affect the daily activities and physical health of people. Inflammatory response accompanies the whole process of jellyfish dermatitis and the complexity of jellyfish venom components makes it difficult to treat jellyfish dermatitis symptoms effectively. Moreover, inhibiting inflammation is essential for the treatment of jellyfish stings and exploring the main components of jellyfish venom that cause inflammation is an urgent research area. In this study, the inhibitory effects of matrix metalloproteinase (MMP) inhibitors for venom-induced inflammation were explored at a cellular level. The expression of the three inflammatory factors, IL-6, TNF-α and MCP-1 in two skin cell lines, human keratinocyte cells (HaCaT) and human embryonic skin fibroblasts cells (CCC-ESF-1), at the cellular level, after treatment with the inhibitors of jellyfish Nemopilema nomurai (N. nomurai) nematocyst venom (NnNV-I), were determined. The results showed that inhibitors of MMP can significantly reduce the toxic effects of jellyfish Nemopilema nomurai nematocyst venom (NnNV) to skin cells. The expression levels of the three inflammatory factors IL-6, MCP-1, and TNF-α in the cells were also significantly decreased, indicating that MMPs in jellyfish venom are probably vital factors leading to jellyfish dermatitis. This study is beneficial in the prevention and treatment of jellyfish stings. Full article
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36 pages, 3751 KiB  
Review
The Toxins of Nemertean Worms
by Ulf Göransson, Erik Jacobsson, Malin Strand and Håkan S. Andersson
Toxins 2019, 11(2), 120; https://doi.org/10.3390/toxins11020120 - 15 Feb 2019
Cited by 29 | Viewed by 14792
Abstract
Most ribbon worms (phylum: Nemertea) are found in marine environments, where they act as predators and scavengers. They are characterized by an eversible proboscis that is used to hunt for prey and thick mucus covering their skin. Both proboscis and epidermal mucus mediate [...] Read more.
Most ribbon worms (phylum: Nemertea) are found in marine environments, where they act as predators and scavengers. They are characterized by an eversible proboscis that is used to hunt for prey and thick mucus covering their skin. Both proboscis and epidermal mucus mediate toxicity to predators and preys. Research into the chemical nature of the substances that render toxicity has not been extensive, but it has nevertheless led to the identification of several compounds of potential medicinal use or for application in biotechnology. This review provides a complete account of the current status of research into nemertean toxins. Full article
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26 pages, 3562 KiB  
Article
RNA-Seq Transcriptome Profiling of the Queen Scallop (Aequipecten opercularis) Digestive Gland after Exposure to Domoic Acid-Producing Pseudo-nitzschia
by Pablo Ventoso, Antonio J. Pazos, M. Luz Pérez-Parallé, Juan Blanco, Juan C. Triviño and José L. Sánchez
Toxins 2019, 11(2), 97; https://doi.org/10.3390/toxins11020097 - 06 Feb 2019
Cited by 16 | Viewed by 5673
Abstract
Some species of the genus Pseudo-nitzschia produce the toxin domoic acid, which causes amnesic shellfish poisoning (ASP). Given that bivalve mollusks are filter feeders, they can accumulate these toxins in their tissues. To elucidate the transcriptional response of the queen scallop Aequipecten opercularis [...] Read more.
Some species of the genus Pseudo-nitzschia produce the toxin domoic acid, which causes amnesic shellfish poisoning (ASP). Given that bivalve mollusks are filter feeders, they can accumulate these toxins in their tissues. To elucidate the transcriptional response of the queen scallop Aequipecten opercularis after exposure to domoic acid-producing Pseudo-nitzschia, the digestive gland transcriptome was de novo assembled using an Illumina HiSeq 2000 platform. Then, a differential gene expression analysis was performed. After the assembly, 142,137 unigenes were obtained, and a total of 10,144 genes were differentially expressed in the groups exposed to the toxin. Functional enrichment analysis found that 374 Pfam (protein families database) domains were significantly enriched. The C1q domain, the C-type lectin, the major facilitator superfamily, the immunoglobulin domain, and the cytochrome P450 were among the most enriched Pfam domains. Protein network analysis showed a small number of highly connected nodes involved in specific functions: proteasome components, mitochondrial ribosomal proteins, protein translocases of mitochondrial membranes, cytochromes P450, and glutathione S-transferases. The results suggest that exposure to domoic acid-producing organisms causes oxidative stress and mitochondrial dysfunction. The transcriptional response counteracts these effects with the up-regulation of genes coding for some mitochondrial proteins, proteasome components, and antioxidant enzymes (glutathione S-transferases, thioredoxins, glutaredoxins, and copper/zinc superoxide dismutases). Full article
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19 pages, 1616 KiB  
Article
Structure Elucidation and Biological Evaluation of Maitotoxin-3, a Homologue of Gambierone, from Gambierdiscus belizeanus
by Andrea Boente-Juncal, Mercedes Álvarez, Álvaro Antelo, Inés Rodríguez, Kevin Calabro, Carmen Vale, Olivier P. Thomas and Luis M. Botana
Toxins 2019, 11(2), 79; https://doi.org/10.3390/toxins11020079 - 01 Feb 2019
Cited by 39 | Viewed by 7881
Abstract
Gambierdiscus species are the producers of the marine toxins ciguatoxins and maitotoxins which cause worldwide human intoxications recognized as Ciguatera Fish Poisoning. A deep chemical investigation of a cultured strain of G. belizeanus, collected in the Caribbean Sea, led to the identification [...] Read more.
Gambierdiscus species are the producers of the marine toxins ciguatoxins and maitotoxins which cause worldwide human intoxications recognized as Ciguatera Fish Poisoning. A deep chemical investigation of a cultured strain of G. belizeanus, collected in the Caribbean Sea, led to the identification of a structural homologue of the recently described gambierone isolated from the same strain. The structure was elucidated mainly by comparison of NMR and MS data with those of gambierone and ascertained by 2D NMR data analyses. Gratifyingly, a close inspection of the MS data of the new 44-methylgambierone suggests that this toxin would actually correspond to the structure of maitotoxin-3 (MTX3, m/z 1039.4957 for the protonated adduct) detected in 1994 in a Pacific strain of Gambierdiscus and recently shown in routine monitoring programs. Therefore, this work provides for the first time the chemical identification of the MTX3 molecule by NMR. Furthermore, biological data confirmed the similar activities of both gambierone and 44-methylgambierone. Both gambierone and MTX3 induced a small increase in the cytosolic calcium concentration but only MTX3 caused cell cytotoxicity at micromolar concentrations. Moreover, chronic exposure of human cortical neurons to either gambierone or MTX3 altered the expression of ionotropic glutamate receptors, an effect already described before for the synthetic ciguatoxin CTX3C. However, even when gambierone and MTX3 affected glutamate receptor expression in a similar manner their effect on receptor expression differed from that of CTX3C, since both toxins decreased AMPA receptor levels while increasing N-methyl-d-aspartate (NMDA) receptor protein. Thus, further studies should be pursued to clarify the similarities and differences in the biological activity between the known ciguatoxins and the new identified molecule as well as its contribution to the neurological symptoms of ciguatera. Full article
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