Toxicology Research on Cyanotoxins

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Marine and Freshwater Toxins".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 8423

Special Issue Editors


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Guest Editor
Department of Food Science, Toxicology and Legal Medicine, Faculty of Pharmacy, University of Sevilla, 41012 Sevilla, Spain
Interests: toxicology; risk assessment; food safety; cyanotoxins; microcystins; cylindrospermopsin
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Food Science, Toxicology and Legal Medicine, Faculty of Pharmacy, University of Sevilla, 41012 Sevilla, Spain
Interests: toxicology; risk assessment; food safety; cyanotoxins; microcystins; cylindrospermopsin
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cyanotoxins are gaining prominence due to their growing occurrence and the worldwide distribution of cyanobacterial blooms, favoured by the present situation of climate change. They can induce a wide range of toxic effects at different levels, from molecular changes to death to humans and wildlife. There are hepatotoxic, neurotoxic and cytotoxic cyanotoxins, among others. Moreover, although they are found mainly in water, they can be accumulated in plants and fish and can be transferred to the trophic chain, and are a global hazard. In the frame of the “One Health” approach, a great deal of work can be done to reduce health threats (cyanotoxins in this case) at the human–animal–ecosystem interface. This Special Issue welcomes experimental and review papers dealing with any toxicological aspect of cyanotoxins in order to advance our knowledge of their risk assessment and to contribute to the prevention and mitigation of their current and future impact on global health.

Prof. Dr. Ángeles Jos
Prof. Dr. Ana M. Cameán
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

  • cyanotoxins
  • toxicology
  • analytics
  • toxic mechanisms
  • risk assessment

Published Papers (5 papers)

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Research

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19 pages, 5074 KiB  
Article
Integration of Multi-Omics, Histological, and Biochemical Analysis Reveals the Toxic Responses of Nile Tilapia Liver to Chronic Microcystin-LR Exposure
by Yichao Li, Huici Yang, Bing Fu, Gen Kaneko, Hongyan Li, Jingjing Tian, Guangjun Wang, Mingken Wei, Jun Xie and Ermeng Yu
Toxins 2024, 16(3), 149; https://doi.org/10.3390/toxins16030149 - 14 Mar 2024
Viewed by 681
Abstract
Microcystin-LR (MC-LR) is a cyanobacterial metabolite produced during cyanobacterial blooms and is toxic to aquatic animals, and the liver is the main targeted organ of MC-LR. To comprehensively understand the toxicity mechanism of chronic exposure to environmental levels of MC-LR on the liver [...] Read more.
Microcystin-LR (MC-LR) is a cyanobacterial metabolite produced during cyanobacterial blooms and is toxic to aquatic animals, and the liver is the main targeted organ of MC-LR. To comprehensively understand the toxicity mechanism of chronic exposure to environmental levels of MC-LR on the liver of fish, juvenile Nile tilapia were exposed to 0 μg/L (control), 1 μg/L (M1), 3 μg/L (M3), 10 μg/L (M10), and 30 μg/L (M30) MC-LR for 60 days. Then, the liver hepatotoxicity induced by MC-LR exposure was systematically evaluated via histological and biochemical determinations, and the underlying mechanisms were explored through combining analysis of biochemical parameters, multi-omics (transcriptome and metabolome), and gene expression. The results exhibited that chronic MC-LR exposure caused slight liver minor structural damage and lipid accumulation in the M10 group, while resulting in serious histological damage and lipid accumulation in the M30 group, indicating obvious hepatotoxicity, which was confirmed by increased toxicity indexes (i.e., AST, ALT, and AKP). Transcriptomic and metabolomic analysis revealed that chronic MC-LR exposure induced extensive changes in gene expression and metabolites in six typical pathways, including oxidative stress, apoptosis, autophagy, amino acid metabolism, primary bile acid biosynthesis, and lipid metabolism. Taken together, chronic MC-LR exposure induced oxidative stress, apoptosis, and autophagy, inhibited primary bile acid biosynthesis, and caused fatty deposition in the liver of Nile tilapia. Full article
(This article belongs to the Special Issue Toxicology Research on Cyanotoxins)
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13 pages, 440 KiB  
Article
Effects of the Toxic Non-Protein Amino Acid β-Methylamino-L-Alanine (BMAA) on Intracellular Amino Acid Levels in Neuroblastoma Cells
by Jake P. Violi, Lisa Pu, Sercan Pravadali-Cekic, David P. Bishop, Connor R. Phillips and Kenneth J. Rodgers
Toxins 2023, 15(11), 647; https://doi.org/10.3390/toxins15110647 - 09 Nov 2023
Cited by 1 | Viewed by 1364
Abstract
The cyanobacterial non-protein amino acid (AA) β-Methylamino-L-alanine (BMAA) is considered to be a neurotoxin. BMAA caused histopathological changes in brains and spinal cords of primates consistent with some of those seen in early motor neuron disease; however, supplementation with L-serine protected against some [...] Read more.
The cyanobacterial non-protein amino acid (AA) β-Methylamino-L-alanine (BMAA) is considered to be a neurotoxin. BMAA caused histopathological changes in brains and spinal cords of primates consistent with some of those seen in early motor neuron disease; however, supplementation with L-serine protected against some of those changes. We examined the impact of BMAA on AA concentrations in human neuroblastoma cells in vitro. Cells were treated with 1000 µM BMAA and intracellular free AA concentrations in treated and control cells were compared at six time-points over a 48 h culture period. BMAA had a profound effect on intracellular AA levels at specific time points but in most cases, AA homeostasis was re-established in the cell. The most heavily impacted amino acid was serine which was depleted in BMAA-treated cells from 9 h onwards. Correction of serine depletion could be a factor in the observation that supplementation with L-serine protects against BMAA toxicity in vitro and in vivo. AAs that could potentially be involved in protection against BMAA-induced oxidation such as histidine, tyrosine, and phenylalanine were depleted in cells at later time points. Full article
(This article belongs to the Special Issue Toxicology Research on Cyanotoxins)
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12 pages, 334 KiB  
Article
In Vitro Mutagenic and Genotoxic Assessment of Anatoxin-a Alone and in Combination with Cylindrospermopsin
by Cristina Plata-Calzado, Leticia Diez-Quijada, Concepción Medrano-Padial, Ana I. Prieto, Ana M. Cameán and Angeles Jos
Toxins 2023, 15(7), 458; https://doi.org/10.3390/toxins15070458 - 13 Jul 2023
Cited by 1 | Viewed by 1019
Abstract
Anatoxin-a (ATX-a) is a cyanobacterial toxin whose occurrence has been reported worldwide and has attracted increasing scientific interest due to its toxicity. Moreover, in nature, ATX-a usually appears together with other cyanotoxins, such as cylindrospermopsin (CYN), so possible interaction phenomena could happen and [...] Read more.
Anatoxin-a (ATX-a) is a cyanobacterial toxin whose occurrence has been reported worldwide and has attracted increasing scientific interest due to its toxicity. Moreover, in nature, ATX-a usually appears together with other cyanotoxins, such as cylindrospermopsin (CYN), so possible interaction phenomena could happen and should be considered for risk assessment purposes. For this reason, the aim of this work was to explore the potential mutagenicity and genotoxicity of pure ATX-a and an ATX-a/CYN mixture using a battery of in vitro assays, including the bacterial reverse-mutation assay in Salmonella typhimurium (OECD 471) and the micronucleus test (MN) (OECD 487) on L5178Y Tk+/− cells. The results showed that ATX-a was not mutagenic either alone or in combination with CYN under the conditions tested. Nevertheless, genotoxic effects were observed for both ATX-a and its mixture with CYN following the in vitro MN assay. The genotoxicity exhibited by ATX-a was only observed in the absence of S9 mix, whereas in the cyanotoxin mixture the concentration-dependent genotoxicity of ATX-a/CYN in vitro was observed only in the presence of S9. Thus, the toxicity induced by cyanotoxin mixtures may vary from that produced by toxins alone, and consequently more studies are necessary in order to perform more realistic risk assessments. Full article
(This article belongs to the Special Issue Toxicology Research on Cyanotoxins)
15 pages, 3169 KiB  
Article
Immunomodulatory Effects of Cylindrospermopsin in Human T Cells and Monocytes
by Antonio Casas-Rodríguez, Óscar Cebadero-Dominguez, María Puerto, Ana María Cameán and Angeles Jos
Toxins 2023, 15(4), 301; https://doi.org/10.3390/toxins15040301 - 20 Apr 2023
Cited by 2 | Viewed by 1505
Abstract
Cylindrospermopsin (CYN) is a cyanotoxin with an increasing occurrence, and therefore it is important to elucidate its toxicity profile. CYN has been classified as a cytotoxin, although the scientific literature has already revealed that it affects a wide range of organs and systems. [...] Read more.
Cylindrospermopsin (CYN) is a cyanotoxin with an increasing occurrence, and therefore it is important to elucidate its toxicity profile. CYN has been classified as a cytotoxin, although the scientific literature has already revealed that it affects a wide range of organs and systems. However, research on its potential immunotoxicity is still limited. Thus, this study aimed to evaluate the impact of CYN on two human cell lines representative of the immune system: THP-1 (monocytes) and Jurkat (lymphocytes). CYN reduced cell viability, leading to mean effective concentrations (EC50 24 h) of 6.00 ± 1.04 µM and 5.20 ± 1.20 µM for THP-1 and Jurkat cells, respectively, and induced cell death mainly by apoptosis in both experimental models. Moreover, CYN decreased the differentiation of monocytes to macrophages after 48 h of exposure. In addition, an up-regulation of the mRNA expression of different cytokines, such as interleukin (IL) 2, IL-8, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (INF-γ), was also observed mainly after 24 h exposure in both cell lines. However, only an increase in TNF-α in THP-1 supernatants was observed by ELISA. Overall, these results suggest the immunomodulatory activity of CYN in vitro. Therefore, further research is required to evaluate the impact of CYN on the human immune system. Full article
(This article belongs to the Special Issue Toxicology Research on Cyanotoxins)
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Review

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40 pages, 525 KiB  
Review
Potential Endocrine Disruption of Cyanobacterial Toxins, Microcystins and Cylindrospermopsin: A Review
by Antonio Casas-Rodriguez, Ana M. Cameán and Angeles Jos
Toxins 2022, 14(12), 882; https://doi.org/10.3390/toxins14120882 - 17 Dec 2022
Cited by 10 | Viewed by 3272
Abstract
Microcystins (MCs) and cylindrospermopsin (CYN), although classified as hepatotoxins and cytotoxins, respectively, have been shown to also induce toxic effects in many other systems and organs. Among them, their potential endocrine disruption (ED) activity has been scarcely investigated. Considering the increasing relevance of [...] Read more.
Microcystins (MCs) and cylindrospermopsin (CYN), although classified as hepatotoxins and cytotoxins, respectively, have been shown to also induce toxic effects in many other systems and organs. Among them, their potential endocrine disruption (ED) activity has been scarcely investigated. Considering the increasing relevance of ED on humans, mammals, and aquatic organisms, this work aimed to review the state-of-the-art regarding the toxic effects of MCs and CYN at this level. It has been evidenced that MCs have been more extensively investigated than CYN. Reported results are contradictory, with the presence or absence of effects, but experimental conditions also vary to a great extent. In general, both toxins have shown ED activity mediated by very different mechanisms, such as estrogenic responses via a binding estrogen receptor (ER), pathological changes in several organs and cells (testis, ovarian cells), and a decreased gonad-somatic index. Moreover, toxic effects mediated by reactive oxygen species (ROS), changes in transcriptional responses on several endocrine axes and steroidogenesis-related genes, and changes in hormone levels have also been reported. Further research is required in a risk assessment frame because official protocols for assessment of endocrine disrupters have not been used. Moreover, the use of advanced techniques would aid in deciphering cyanotoxins dose-response relationships in relation to their ED potential. Full article
(This article belongs to the Special Issue Toxicology Research on Cyanotoxins)
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