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Analytical, Toxicological and Molecular Biological Assessment of Cyanobacterial Toxins

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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 May 2022) | Viewed by 9083

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Special Issue Editors

Prof. Dr. Ángeles Jos

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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

Prof. Dr. Ana M. Cameán

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Special Issue Information

Dear Colleagues,

Cyanobacterial toxins are a focus of interest for several reasons. Cyanobacterial blooms are becoming more and more frequently reported, and their increasing distribution makes cyanotoxins occurrence a worldwide health problem. Cyanobacteria and cyanotoxins have an impact not only on humans but also on the environment. Thus, apart from human poisonings from different exposure routes, they can cause toxicity and even mortality in fish, plants, cattle, etc. that can lead to changes in ecosystems composition and loss of biodiversity, among other consequences. Therefore, they are involved in acute toxicosis, but are predominantly associated with long-term deleterious effects. Note that no regulatory limits have been established for the majority of them so far. An increase in the available knowledge of their toxic effects, their molecular mechanisms of action, and the development of improved analytical methods for their determination and quantification will contribute to a better evaluation of their risks, and will help to promote public health. Accordingly, the aim of this Special Issue is to foster cyanobacterial toxins research, particularly in relation to microcystins and cylindrospermopsin, due to their toxicity and ubiquity. Thus, both primary research and comprehensive review papers are welcome in order to provide up-to-date findings regarding their toxicological profile, potential mitigation of their health effects, consequences of their concomitant exposure, analytical challenges, the use of advanced molecular tools, and all other aspects that allow us to obtain further knowledge of these cyanotoxins.

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.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

cyanotoxins
microcystins
cylindrospermopsin
toxicity
analysis
risk assessment
mechanisms of action

Published Papers (4 papers)

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Research

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11 pages, 1497 KiB

Open AccessArticle

Impact of Cyanotoxin Ingestion on Liver Cancer Development Using an At-Risk Two-Staged Model of Mouse Hepatocarcinogenesis

by Igor Mrdjen, Jiyoung Lee, Christopher M. Weghorst and Thomas J. Knobloch

Toxins 2022, 14(7), 484; https://doi.org/10.3390/toxins14070484 - 14 Jul 2022

Cited by 4 | Viewed by 1787

Abstract

Exposure to cyanobacterial hepatotoxins has been linked to the promotion and increased incidence of liver cancer in pre-clinical and epidemiologic studies. The family of hepatotoxins, microcystins (MCs), are produced by over 40 cyanobacterial species found in harmful algal blooms (HABs) worldwide, with MC-LR being the most common and potent MC congener. In the current study, we hypothesized that the low-dose chronic ingestion of Microcystis cyanotoxins via drinking water would promote liver carcinogenesis in pre-initiated mice. Four groups of C3H/HeJ mice received one intraperitoneal (i.p.) injection of diethylnitrosamine (DEN) at 4 weeks of age. Three weeks later, the mice were administered ad libitum drinking water containing one of the following: (1) reverse osmosis, deionized water; (2) water containing 500 mg/L phenobarbital (PB500); (3) water with purified MC-LR (10 µg/L) added; or (4) water containing lysed Microcystis aeruginosa (lysate; 10 µg/L total MCs). The exposure concentrations were based on environmentally relevant concentrations and previously established Ohio EPA recreational water MC guidelines. Throughout the 30-week exposure, mouse weights, food consumption, and water consumption were not significantly impacted by toxin ingestion. We found no significant differences in the number of gross and histopathologic liver lesion counts across the treatment groups, but we did note that the PB500 group developed lesion densities too numerous to count. Additionally, the proportion of lesions classified as hepatocellular carcinomas in the MC-LR group (44.5%; p < 0.05) and lysate group (55%; p < 0.01) was significantly higher compared to the control group (14.9%). Over the course of the study, the mice ingesting the lysate also had a significantly lower survival probability (64.4%; p < 0.001) compared to water (96.8%), PB500 (95.0%), and MC-LR (95.7%) exposures. Using cyanotoxin levels at common recreational water concentration levels, we demonstrate the cancer-promoting effects of a single cyanotoxin MC congener (MC-LR). Furthermore, we show enhanced hepatocarcinogenesis and significant mortality associated with combinatorial exposure to the multiple MCs and bioactive compounds present in lysed cyanobacterial cells—a scenario representative of the ingestion exposure route, such as HAB-contaminated water and food. Full article

(This article belongs to the Special Issue Analytical, Toxicological and Molecular Biological Assessment of Cyanobacterial Toxins)

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20 pages, 888 KiB

Open AccessArticle

In Vitro Toxicity Evaluation of Cyanotoxins Cylindrospermopsin and Microcystin-LR on Human Kidney HEK293 Cells

by Leticia Diez-Quijada, María Puerto, Daniel Gutiérrez-Praena, Maria V. Turkina, Alexandre Campos, Vitor Vasconcelos, Ana M. Cameán and Ángeles Jos

Toxins 2022, 14(7), 429; https://doi.org/10.3390/toxins14070429 - 23 Jun 2022

Cited by 3 | Viewed by 2147

Abstract

Cyanotoxins are secondary metabolites produced by different types of cyanobacteria. Among them, Cylindrospermopsin (CYN) and Microcystins (MCs) stand out due to their wide geographical distribution and toxicity in various organs, including the kidney, which is involved in their distribution and elimination. However, the renal toxicity caused by CYN and MCs has hardly been studied. The aim of this work was to assess the cytotoxicity effects caused by CYN and MC-LR in the renal cell line HEK293, and for the first time, the influence of CYN on the gene expression of selected genes in these cells by quantitative real-time PCR (qRT-PCR). CYN caused an upregulation in the gene expression after exposure to the highest concentration (5 µg/mL) and the longest time of exposure (24 h). Moreover, shotgun proteomic analysis was used to assess the molecular responses of HEK293 cells after exposure to the individuals and combinations of CYN + MC-LR. The simultaneous exposure to both cyanotoxins caused a greater number of alterations in protein expression compared to single toxins, causing changes in the cellular, lipid and protein metabolism and in protein synthesis and transport. Further studies are needed to complete the toxicity molecular mechanisms of both CYN and MC-LR at the renal level. Full article

(This article belongs to the Special Issue Analytical, Toxicological and Molecular Biological Assessment of Cyanobacterial Toxins)

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18 pages, 2310 KiB

Open AccessArticle

Immunomodulatory Effects of Pure Cylindrospermopsin in Rats Orally Exposed for 28 Days

by Leticia Diez-Quijada, Antonio Casas-Rodriguez, Remedios Guzmán-Guillén, Verónica Molina-Hernández, Rafael G. Albaladejo, Ana María Cameán and Angeles Jos

Toxins 2022, 14(2), 144; https://doi.org/10.3390/toxins14020144 - 15 Feb 2022

Cited by 7 | Viewed by 1963

Abstract

Cylindrospermopsin (CYN) is a ubiquitous cyanotoxin showing increasing incidence worldwide. CYN has been classified as a cytotoxin and, among its toxic effects, its immunotoxicity is scarcely studied. This work investigates for the first time the influence of oral CYN exposure (18.75; 37.5 and 75 µg/kg b.w./day, for 28 days) on the mRNA expression of selected interleukin (IL) genes (IL-1β, IL-2, IL-6, Tumor Necrosis Factor alpha (TNF-α), Interferon gamma (IFN-γ)) in the thymus and the spleen of male and female rats, by quantitative real-time polymerase chain reaction (RT-qPCR). Moreover, their serum levels were also measured by a multiplex-bead-based immunoassay, and a histopathological study was performed. CYN produced immunomodulation mainly in the thymus of rats exposed to 75 μg CYN/kg b.w./day in both sexes. However, in the spleen only IL-1β and IL-2 (males), and TNF-α and IFN-γ (females) expression was modified after CYN exposure. Only female rats exposed to 18.75 μg CYN/kg b.w./day showed a significant decrease in TNF-α serum levels. There were no significant differences in the weight or histopathology in the organs studied. Further research is needed to obtain a deeper view of the molecular mechanisms involved in CYN immunotoxicity and its consequences on long-term exposures. Full article

(This article belongs to the Special Issue Analytical, Toxicological and Molecular Biological Assessment of Cyanobacterial Toxins)

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Review

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27 pages, 766 KiB

Open AccessReview

Immunotoxic Effects Induced by Microcystins and Cylindrospermopsin: A Review

by Leticia Diez-Quijada, Maria del Monte Benítez-González, María Puerto, Angeles Jos and Ana M. Cameán

Toxins 2021, 13(10), 711; https://doi.org/10.3390/toxins13100711 - 08 Oct 2021

Cited by 20 | Viewed by 2534

Abstract

Cyanotoxin occurrence is gaining importance due to anthropogenic activities, climate change and eutrophication. Among them, Microcystins (MCs) and Cylindrospermopsin (CYN) are the most frequently studied due to their ubiquity and toxicity. Although MCs are primary classified as hepatotoxins and CYN as a cytotoxin, they have been shown to induce deleterious effects in a wide range of organs. However, their effects on the immune system are as yet scarcely investigated. Thus, to know the impact of cyanotoxins on the immune system, due to its importance in organisms’ homeostasis, is considered of interest. A review of the scientific literature dealing with the immunotoxicity of MCs and CYN has been performed, and both in vitro and in vivo studies have been considered. Results have confirmed the scarcity of reports on the topic, particularly for CYN. Decreased cell viability, apoptosis or altered functions of immune cells, and changed levels and mRNA expression of cytokines are among the most common effects reported. Underlying mechanisms, however, are still not yet fully elucidated. Further research is needed in order to have a full picture of cyanotoxin immunotoxicity. Full article

(This article belongs to the Special Issue Analytical, Toxicological and Molecular Biological Assessment of Cyanobacterial Toxins)

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