Toxins

23 pages, 951 KiB

Open AccessEditor’s ChoiceReview

Antibodies and Vaccines against Botulinum Toxins: Available Measures and Novel Approaches

by Christine Rasetti-Escargueil and Michel R. Popoff

Toxins 2019, 11(9), 528; https://doi.org/10.3390/toxins11090528 - 12 Sep 2019

Cited by 37 | Viewed by 10854

Botulinum neurotoxin (BoNT) is produced by the anaerobic, Gram-positive bacterium Clostridium botulinum. As one of the most poisonous toxins known and a potential bioterrosism agent, BoNT is characterized by a complex mode of action comprising: internalization, translocation and proteolytic cleavage of a [...] Read more.

Botulinum neurotoxin (BoNT) is produced by the anaerobic, Gram-positive bacterium Clostridium botulinum. As one of the most poisonous toxins known and a potential bioterrosism agent, BoNT is characterized by a complex mode of action comprising: internalization, translocation and proteolytic cleavage of a substrate, which inhibits synaptic exocytotic transmitter release at neuro-muscular nerve endings leading to peripheral neuroparalysis of the skeletal and autonomic nervous systems. There are seven major serologically distinct toxinotypes (A–G) of BoNT which act on different substrates. Human botulism is generally caused by BoNT/A, B and E. Due to its extreme lethality and potential use as biological weapon, botulism remains a global public health concern. Vaccination against BoNT, although an effective strategy, remains undesirable due to the growing expectation around therapeutic use of BoNTs in various pathological conditions. This review focuses on the current approaches for botulism control by immunotherapy, highlighting the future challenges while the molecular underpinnings among subtypes variants and BoNT sequences found in non-clostridial species remain to be elucidated. Full article

(This article belongs to the Special Issue Characterization and Quantitative Analysis of Botulinum Neurotoxin)

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33 pages, 1826 KiB

Open AccessEditor’s ChoiceReview

New Insights into the Roles of Monocytes/Macrophages in Cardiovascular Calcification Associated with Chronic Kidney Disease

by Lucie Hénaut, Alexandre Candellier, Cédric Boudot, Maria Grissi, Romuald Mentaverri, Gabriel Choukroun, Michel Brazier, Saïd Kamel and Ziad A. Massy

Toxins 2019, 11(9), 529; https://doi.org/10.3390/toxins11090529 - 12 Sep 2019

Cited by 36 | Viewed by 5530

Abstract

Cardiovascular disease (CVD) is an important cause of death in patients with chronic kidney disease (CKD), and cardiovascular calcification (CVC) is one of the strongest predictors of CVD in this population. Cardiovascular calcification results from complex cellular interactions involving the endothelium, vascular/valvular cells [...] Read more.

Cardiovascular disease (CVD) is an important cause of death in patients with chronic kidney disease (CKD), and cardiovascular calcification (CVC) is one of the strongest predictors of CVD in this population. Cardiovascular calcification results from complex cellular interactions involving the endothelium, vascular/valvular cells (i.e., vascular smooth muscle cells, valvular interstitial cells and resident fibroblasts), and monocyte-derived macrophages. Indeed, the production of pro-inflammatory cytokines and oxidative stress by monocyte-derived macrophages is responsible for the osteogenic transformation and mineralization of vascular/valvular cells. However, monocytes/macrophages show the ability to modify their phenotype, and consequently their functions, when facing environmental modifications. This plasticity complicates efforts to understand the pathogenesis of CVC—particularly in a CKD setting, where both uraemic toxins and CKD treatment may affect monocyte/macrophage functions and thereby influence CVC. Here, we review (i) the mechanisms by which each monocyte/macrophage subset either promotes or prevents CVC, and (ii) how both uraemic toxins and CKD therapies might affect these monocyte/macrophage functions. Full article

(This article belongs to the Special Issue The Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD))

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11 pages, 1582 KiB

Open AccessEditor’s ChoiceArticle

Aflatoxin B₁ Conversion by Black Soldier Fly (Hermetia illucens) Larval Enzyme Extracts

by Nathan Meijer, Geert Stoopen, H.J. van der Fels-Klerx, Joop J.A. van Loon, John Carney and Guido Bosch

Toxins 2019, 11(9), 532; https://doi.org/10.3390/toxins11090532 - 12 Sep 2019

Cited by 31 | Viewed by 7176

Abstract

The larvae of the black soldier fly (Hermetia illucens L., BSFL) have received increased industrial interest as a novel protein source for food and feed. Previous research has found that insects, including BSFL, are capable of metabolically converting aflatoxin B₁ (AFB [...] Read more.

The larvae of the black soldier fly (Hermetia illucens L., BSFL) have received increased industrial interest as a novel protein source for food and feed. Previous research has found that insects, including BSFL, are capable of metabolically converting aflatoxin B₁ (AFB₁), but recovery of total AFB₁ is less than 20% when accounting for its conversion to most known metabolites. The aim of this study was to examine the conversion of AFB₁ by S9 extracts of BSFL reared on substrates with or without AFB₁. Liver S9 of Aroclor-induced rats was used as a reference. To investigate whether cytochrome P450 enzymes are involved in the conversion of AFB₁, the inhibitor piperonyl butoxide (PBO) was tested in a number of treatments. The results showed that approximately 60% of AFB₁ was converted to aflatoxicol and aflatoxin P₁. The remaining 40% of AFB₁ was not converted. Cytochrome P450s were indeed responsible for metabolic conversion of AFB₁ into AFP₁, and a cytoplasmic reductase was most likely responsible for conversion of AFB₁ into aflatoxicol. Full article

(This article belongs to the Special Issue Mycotoxins in Feed and Food Chain: Present Status and Future Concerns)

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34 pages, 2898 KiB

Open AccessEditor’s ChoiceReview

The Diversity of Cyanobacterial Toxins on Structural Characterization, Distribution and Identification: A Systematic Review

by Xingde Du, Haohao Liu, Le Yuan, Yueqin Wang, Ya Ma, Rui Wang, Xinghai Chen, Michael D. Losiewicz, Hongxiang Guo and Huizhen Zhang

Toxins 2019, 11(9), 530; https://doi.org/10.3390/toxins11090530 - 12 Sep 2019

Cited by 118 | Viewed by 9203

Abstract

The widespread distribution of cyanobacteria in the aquatic environment is increasing the risk of water pollution caused by cyanotoxins, which poses a serious threat to human health. However, the structural characterization, distribution and identification techniques of cyanotoxins have not been comprehensively reviewed in [...] Read more.

The widespread distribution of cyanobacteria in the aquatic environment is increasing the risk of water pollution caused by cyanotoxins, which poses a serious threat to human health. However, the structural characterization, distribution and identification techniques of cyanotoxins have not been comprehensively reviewed in previous studies. This paper aims to elaborate the existing information systematically on the diversity of cyanotoxins to identify valuable research avenues. According to the chemical structure, cyanotoxins are mainly classified into cyclic peptides, alkaloids, lipopeptides, nonprotein amino acids and lipoglycans. In terms of global distribution, the amount of cyanotoxins are unbalanced in different areas. The diversity of cyanotoxins is more obviously found in many developed countries than that in undeveloped countries. Moreover, the threat of cyanotoxins has promoted the development of identification and detection technology. Many emerging methods have been developed to detect cyanotoxins in the environment. This communication provides a comprehensive review of the diversity of cyanotoxins, and the detection and identification technology was discussed. This detailed information will be a valuable resource for identifying the various types of cyanotoxins which threaten the environment of different areas. The ability to accurately identify specific cyanotoxins is an obvious and essential aspect of cyanobacterial research. Full article

(This article belongs to the Special Issue Cyanobacterial Toxins: Identification and Structural Characterisation to Better Understand Their Distribution and Diversity)

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15 pages, 1415 KiB

Open AccessEditor’s ChoiceArticle

Detoxification of the Fumonisin Mycotoxins in Maize: An Enzymatic Approach

by Johanna Alberts, Gerd Schatzmayr, Wulf-Dieter Moll, Ibtisaam Davids, John Rheeder, Hester-Mari Burger, Gordon Shephard and Wentzel Gelderblom

Toxins 2019, 11(9), 523; https://doi.org/10.3390/toxins11090523 - 10 Sep 2019

Cited by 27 | Viewed by 5037

Abstract

Enzymatic detoxification has become a promising approach for control of mycotoxins postharvest in grains through modification of chemical structures determining their toxicity. In the present study fumonisin esterase FumD (EC 3.1.1.87) (FUMzyme^®; BIOMIN, Tulln, Austria), hydrolysing fumonisin (FB) mycotoxins by [...] Read more.

Enzymatic detoxification has become a promising approach for control of mycotoxins postharvest in grains through modification of chemical structures determining their toxicity. In the present study fumonisin esterase FumD (EC 3.1.1.87) (FUMzyme^®; BIOMIN, Tulln, Austria), hydrolysing fumonisin (FB) mycotoxins by de-esterification, was utilised to develop an enzymatic reduction method in a maize kernel enzyme incubation mixture. Efficacy of the FumD FB reduction method in “low” and “high” FB contaminated home-grown maize was compared by monitoring FB₁ hydrolysis to the hydrolysed FB₁ (HFB₁) product utilising a validated LC-MS/MS analytical method. The method was further evaluated in terms of enzyme activity and treatment duration by assessing enzyme kinetic parameters and the relative distribution of HFB₁ between maize kernels and the residual aqueous environment. FumD treatments resulted in significant reduction (≥80%) in “low” (≥1000 U/L, p < 0.05) and “high” (100 U/L, p < 0.05; ≥1000 U/L, p < 0.0001) FB contaminated maize after 1 h respectively, with an approximate 1:1 µmol conversion ratio of FB₁ into the formation of HFB₁. Enzyme kinetic parameters indicated that, depending on the activity of FumD utilised, a significantly (p < 0.05) higher FB₁ conversion rate was noticed in “high” FB contaminated maize. The FumD FB reduction method in maize could find application in commercial maize-based practices as well as in communities utilising home-grown maize as a main dietary staple and known to be exposed above the tolerable daily intake levels. Full article

(This article belongs to the Special Issue Novel Approaches to Minimising Mycotoxin Contamination)

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17 pages, 1469 KiB

Open AccessEditor’s ChoiceReview

Modifying Phosphate Toxicity in Chronic Kidney Disease

by Marc Vervloet

Toxins 2019, 11(9), 522; https://doi.org/10.3390/toxins11090522 - 9 Sep 2019

Cited by 16 | Viewed by 5332

Abstract

Phosphate toxicity is a well-established phenomenon, especially in chronic kidney disease (CKD), where hyperphosphatemia is a frequent occurrence when CKD is advanced. Many therapeutic efforts are targeted at phosphate, and comprise dietary intervention, modifying dialysis schemes, treating uncontrolled hyperparathyroidism and importantly, phosphate binder [...] Read more.

Phosphate toxicity is a well-established phenomenon, especially in chronic kidney disease (CKD), where hyperphosphatemia is a frequent occurrence when CKD is advanced. Many therapeutic efforts are targeted at phosphate, and comprise dietary intervention, modifying dialysis schemes, treating uncontrolled hyperparathyroidism and importantly, phosphate binder therapy. Despite all these interventions, hyperphosphatemia persists in many, and its pathological influence is ongoing. In nephrological care, a somewhat neglected aspect of treatment—when attempts fail to lower exposure to a toxin like phosphate—is to explore the possibility of “anti-dotes”. Indeed, quite a long list of factors modify, or are mediators of phosphate toxicity. Addressing these, especially when phosphate itself cannot be sufficiently controlled, may provide additional protection. In this narrative overview, several factors are discussed that may qualify as either such a modifier or mediator, that can be influenced by other means than simply lowering phosphate exposure. A wider scope when targeting phosphate-induced comorbidity in CKD, in particular cardiovascular disease, may alleviate the burden of disease that is the consequence of this potentially toxic mineral in CKD. Full article

(This article belongs to the Special Issue The Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD))

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22 pages, 1889 KiB

Open AccessEditor’s ChoiceArticle

Development of an UPLC-MS/MS Method for the Analysis of Mycotoxins in Rumen Fluid with and without Maize Silage Emphasizes the Importance of Using Matrix-Matched Calibration

by Sandra Debevere, Siegrid De Baere, Geert Haesaert, Michael Rychlik, Veerle Fievez and Siska Croubels

Toxins 2019, 11(9), 519; https://doi.org/10.3390/toxins11090519 - 7 Sep 2019

Cited by 19 | Viewed by 5019

Abstract

Ruminants are less susceptible to the effects of mycotoxins than monogastric animals as their rumen microbiota are claimed to degrade and/or deactivate at least some of these toxic compounds. However, the mycotoxin degradation is not well-known yet. For this, a sensitive, specific, and [...] Read more.

Ruminants are less susceptible to the effects of mycotoxins than monogastric animals as their rumen microbiota are claimed to degrade and/or deactivate at least some of these toxic compounds. However, the mycotoxin degradation is not well-known yet. For this, a sensitive, specific, and accurate analytical method is needed to determine mycotoxins in the rumen fluid. This study aims to develop and thoroughly validate an ultra-performance liquid chromatography tandem mass spectrometry method for the quantitative determination in the rumen fluid of some of the most relevant mycotoxins found in maize silage in Western Europe: deoxynivalenol (DON), nivalenol (NIV), zearalenone (ZEN), mycophenolic acid (MPA), roquefortine C (ROQ-C) and enniatin B (ENN B), as well as their metabolites deepoxy-deoxynivalenol (DOM-1), α-zearalenol (α-ZEL), β-zearalenol (β-ZEL), zearalanone (ZAN), α-zearalanol (α-ZAL) and β-zearalanol (β-ZAL). As feed is often present in the rumen fluid samples, the potential interaction of feed particles with the mycotoxin extraction and analysis was investigated. Extraction recovery and matrix effects were determined in the rumen fluid with and without maize silage. Differences in those parameters between rumen fluid alone and rumen fluid with maize silage highlight the importance of using matrix-matched calibration curves for the quantification of mycotoxins in rumen fluid samples. A cross-validation of the method with rumen fluid and maize silage demonstrates that this analytical method can be applied in research on rumen fluid samples to investigate the degradation of the reported mycotoxins by rumen microbiota if matrix-matched calibration is performed. Full article

(This article belongs to the Special Issue Application of LC-MS/MS in the Mycotoxins Studies)

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13 pages, 1430 KiB

Open AccessEditor’s ChoiceArticle

Serrulin: A Glycine-Rich Bioactive Peptide from the Hemolymph of the Yellow Tityus serrulatus Scorpion

by Thiago de Jesus Oliveira, Ursula Castro de Oliveira and Pedro Ismael da Silva Junior

Toxins 2019, 11(9), 517; https://doi.org/10.3390/toxins11090517 - 6 Sep 2019

Cited by 18 | Viewed by 4840

Abstract

Antimicrobial peptides (AMPs) are small molecules, which have a potential use as antibiotic or pharmacological tools. In chelicerate organisms, such as scorpions, these molecules constitute an alternative defense system against microorganisms. The aim of this work was to identify AMPs in the hemolymph [...] Read more.

Antimicrobial peptides (AMPs) are small molecules, which have a potential use as antibiotic or pharmacological tools. In chelicerate organisms, such as scorpions, these molecules constitute an alternative defense system against microorganisms. The aim of this work was to identify AMPs in the hemolymph of the Tityus serrulatus scorpion. Fractions of plasma and hemocytes were subjected to high-performance liquid chromatography (HPLC) and then analyzed to determine their activity in inhibiting microbial growth. One of the fractions from the hemocytes presents antimicrobial activity against microorganisms, such as Gram-negative and Gram-positive bacteria, fungi, and yeast. These fractions were analyzed by mass spectrometry, and a fragment of 3564 Da. was identified. The peptide was called serrulin, because it is derived from the species T. serrulatus. A comparison of the amino acid sequence of serrulin with databases shows that it has a similarity to the glycine-rich peptides described in Cupienius salai and Acanthoscurria gomesiana (spiders). Furthermore, serrulin has no hemolytic activity against human erythrocytes. While the presence of AMPs in T. serrulatus venom has been described in other works, this is the first work to characterize the presence of these molecules in the hemolymph (hemocytes) of this species and show its potential use as an alternative to conventional antibiotics against different species of microorganisms. Full article

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21 pages, 786 KiB

Open AccessEditor’s ChoiceReview

Updates on the Effect of Mycotoxins on Male Reproductive Efficiency in Mammals

by Diala El. Khoury, Salma Fayjaloun, Marc Nassar, Joseph Sahakian and Pauline Y. Aad

Toxins 2019, 11(9), 515; https://doi.org/10.3390/toxins11090515 - 3 Sep 2019

Cited by 46 | Viewed by 6873

Abstract

Mycotoxins are ubiquitous and unavoidable harmful fungal products with the ability to cause disease in both animals and humans, and are found in almost all types of foods, with a greater prevalence in hot humid environments. These mycotoxins vary greatly in structure and [...] Read more.

Mycotoxins are ubiquitous and unavoidable harmful fungal products with the ability to cause disease in both animals and humans, and are found in almost all types of foods, with a greater prevalence in hot humid environments. These mycotoxins vary greatly in structure and biochemical effects; therefore, by better understanding the toxicological and pathological aspects of mycotoxins, we can be better equipped to fight the diseases, as well as the biological and economic devastations, they induce. Multiple studies point to the association between a recent increase in male infertility and the increased occurrence of these mycotoxins in the environment. Furthermore, understanding how mycotoxins may induce an accumulation of epimutations during parental lifetimes can shed light on their implications with respect to fertility and reproductive efficiency. By acknowledging the diversity of mycotoxin molecular function and mode of action, this review aims to address the current limited knowledge on the effects of these chemicals on spermatogenesis and the various endocrine and epigenetics patterns associated with their disruptions. Full article

(This article belongs to the Special Issue Dietary Mycotoxin Exposure: Emerging Risks to Human Health)

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25 pages, 7424 KiB

Open AccessEditor’s ChoiceArticle

Comparative Structure–Activity Analysis of the Antimicrobial Activity, Cytotoxicity, and Mechanism of Action of the Fungal Cyclohexadepsipeptides Enniatins and Beauvericin

by Hamza Olleik, Cendrine Nicoletti, Mickael Lafond, Elise Courvoisier-Dezord, Peiwen Xue, Akram Hijazi, Elias Baydoun, Josette Perrier and Marc Maresca

Toxins 2019, 11(9), 514; https://doi.org/10.3390/toxins11090514 - 3 Sep 2019

Cited by 37 | Viewed by 4613

Abstract

Filamentous fungi, although producing noxious molecules such as mycotoxins, have been used to produce numerous drugs active against human diseases such as paclitaxel, statins, and penicillin, saving millions of human lives. Cyclodepsipeptides are fungal molecules with potentially adverse and positive effects. Although these [...] Read more.

Filamentous fungi, although producing noxious molecules such as mycotoxins, have been used to produce numerous drugs active against human diseases such as paclitaxel, statins, and penicillin, saving millions of human lives. Cyclodepsipeptides are fungal molecules with potentially adverse and positive effects. Although these peptides are not novel, comparative studies of their antimicrobial activity, toxicity, and mechanism of action are still to be identified. In this study, the fungal cyclohexadepsipeptides enniatin (ENN) and beauvericin (BEA) were assessed to determine their antimicrobial activity and cytotoxicity against human cells. Results showed that these peptides were active against Gram-positive bacteria, Mycobacterium, and fungi, but not against Gram-negative bacteria. ENN and BEA had a limited hemolytic effect, yet were found to be toxic at low doses to nucleated human cells. Both peptides also interacted with bacterial lipids, causing low to no membrane permeabilization, but induced membrane depolarization and inhibition of macromolecules synthesis. The structure–activity analysis showed that the chemical nature of the side chains present on ENN and BEA (either iso-propyl, sec-butyl, or phenylmethyl) impacts their interaction with lipids, antimicrobial action, and toxicity. Full article

(This article belongs to the Section Mycotoxins)

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13 pages, 894 KiB

Open AccessEditor’s ChoiceArticle

Production of β-methylamino-L-alanine (BMAA) and Its Isomers by Freshwater Diatoms

by Jake P. Violi, Jordan A. Facey, Simon M. Mitrovic, Anne Colville and Kenneth J. Rodgers

Toxins 2019, 11(9), 512; https://doi.org/10.3390/toxins11090512 - 2 Sep 2019

Cited by 38 | Viewed by 6050

Abstract

β-methylamino-L-alanine (BMAA) is a non-protein amino acid that has been implicated as a risk factor for motor neurone disease (MND). BMAA is produced by a wide range of cyanobacteria globally and by a small number of marine diatoms. BMAA is commonly found with [...] Read more.

β-methylamino-L-alanine (BMAA) is a non-protein amino acid that has been implicated as a risk factor for motor neurone disease (MND). BMAA is produced by a wide range of cyanobacteria globally and by a small number of marine diatoms. BMAA is commonly found with two of its constitutional isomers: 2,4-diaminobutyric acid (2,4-DAB), and N-(2-aminoethyl)glycine (AEG). The isomer 2,4-DAB, like BMAA, has neurotoxic properties. While many studies have shown BMAA production by cyanobacteria, few studies have looked at other algal groups. Several studies have shown BMAA production by marine diatoms; however, there are no studies examining freshwater diatoms. This study aimed to determine if some freshwater diatoms produced BMAA, and which diatom taxa are capable of BMAA, 2,4-DAB and AEG production. Five axenic diatom cultures were established from river and lake sites across eastern Australia. Cultures were harvested during the stationary growth phase and intracellular amino acids were extracted. Using liquid chromatography triple quadrupole mass spectrometry (LC-MS/MS), diatom extracts were analysed for the presence of both free and protein-associated BMAA, 2,4-DAB and AEG. Of the five diatom cultures analysed, four were found to have detectable BMAA and AEG, while 2,4-DAB was found in all cultures. These results show that BMAA production by diatoms is not confined to marine genera and that the prevalence of these non-protein amino acids in Australian freshwater environments cannot be solely attributed to cyanobacteria. Full article

(This article belongs to the Special Issue Freshwater Cyanobacterial Toxins: Developments in Monitoring, Identification, Impacts and Factors Influencing Production)

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26 pages, 8963 KiB

Open AccessEditor’s ChoiceArticle

Nigritanine as a New Potential Antimicrobial Alkaloid for the Treatment of Staphylococcus aureus-Induced Infections

by Bruno Casciaro, Andrea Calcaterra, Floriana Cappiello, Mattia Mori, Maria Rosa Loffredo, Francesca Ghirga, Maria Luisa Mangoni, Bruno Botta and Deborah Quaglio

Toxins 2019, 11(9), 511; https://doi.org/10.3390/toxins11090511 - 1 Sep 2019

Cited by 43 | Viewed by 5268

Abstract

Staphylococcus aureus is a major human pathogen causing a wide range of nosocomial infections including pulmonary, urinary, and skin infections. Notably, the emergence of bacterial strains resistant to conventional antibiotics has prompted researchers to find new compounds capable of killing these pathogens. Nature [...] Read more.

Staphylococcus aureus is a major human pathogen causing a wide range of nosocomial infections including pulmonary, urinary, and skin infections. Notably, the emergence of bacterial strains resistant to conventional antibiotics has prompted researchers to find new compounds capable of killing these pathogens. Nature is undoubtedly an invaluable source of bioactive molecules characterized by an ample chemical diversity. They can act as unique platform providing new scaffolds for further chemical modifications in order to obtain compounds with optimized biological activity. A class of natural compounds with a variety of biological activities is represented by alkaloids, important secondary metabolites produced by a large number of organisms including bacteria, fungi, plants, and animals. In this work, starting from the screening of 39 alkaloids retrieved from a unique in-house library, we identified a heterodimer β-carboline alkaloid, nigritanine, with a potent anti-Staphylococcus action. Nigritanine, isolated from Strychnos nigritana, was characterized for its antimicrobial activity against a reference and three clinical isolates of S. aureus. Its potential cytotoxicity was also evaluated at short and long term against mammalian red blood cells and human keratinocytes, respectively. Nigritanine showed a remarkable antimicrobial activity (minimum inhibitory concentration of 128 µM) without being toxic in vitro to both tested cells. The analysis of the antibacterial activity related to the nigritanine scaffold furnished new insights in the structure–activity relationships (SARs) of β-carboline, confirming that dimerization improves its antibacterial activity. Taking into account these interesting results, nigritanine can be considered as a promising candidate for the development of new antimicrobial molecules for the treatment of S. aureus-induced infections. Full article

(This article belongs to the Special Issue Biological Activities of Alkaloids: From Toxicology to Pharmacology)

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20 pages, 1356 KiB

Open AccessEditor’s ChoiceReview

A Review of Cardiovascular Toxicity of Microcystins

by Linghui Cao, Isaac Yaw Massey, Hai Feng and Fei Yang

Toxins 2019, 11(9), 507; https://doi.org/10.3390/toxins11090507 - 30 Aug 2019

Cited by 48 | Viewed by 5107

Abstract

The mortality rate of cardiovascular diseases (CVD) in China is on the rise. The increasing burden of CVD in China has become a major public health problem. Cyanobacterial blooms have been recently considered a global environmental concern. Microcystins (MCs) are the secondary products [...] Read more.

The mortality rate of cardiovascular diseases (CVD) in China is on the rise. The increasing burden of CVD in China has become a major public health problem. Cyanobacterial blooms have been recently considered a global environmental concern. Microcystins (MCs) are the secondary products of cyanobacteria metabolism and the most harmful cyanotoxin found in water bodies. Recent studies provide strong evidence of positive associations between MC exposure and cardiotoxicity, representing a threat to human cardiovascular health. This review focuses on the effects of MCs on the cardiovascular system and provides some evidence that CVD could be induced by MCs. We summarized the current knowledge of the cardiovascular toxicity of MCs, with regard to direct cardiovascular toxicity and indirect cardiovascular toxicity. Toxicity of MCs is mainly governed by the increasing level of reactive oxygen species (ROS), oxidative stress in mitochondria and endoplasmic reticulum, the inhibition activities of serine/threonine protein phosphatase 1 (PP1) and 2A (PP2A) and the destruction of cytoskeletons, which finally induce the occurrence of CVD. To protect human health from the threat of MCs, this paper also puts forward some directions for further research. Full article

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18 pages, 4179 KiB

Open AccessEditor’s ChoiceArticle

Annona cherimola Seed Extract Activates Extrinsic and Intrinsic Apoptotic Pathways in Leukemic Cells

by Tony Haykal, Peter Nasr, Mohammad H. Hodroj, Robin I. Taleb, Rita Sarkis, Marvy Nadine El. Moujabber and Sandra Rizk

Toxins 2019, 11(9), 506; https://doi.org/10.3390/toxins11090506 - 30 Aug 2019

Cited by 24 | Viewed by 10627

Abstract

Annona cherimola Mill is a large green fruit with black seeds widely known to possess toxic properties due to the presence of Annonaceous acetogenins. The present study investigates the anti-cancer properties of an Annona cherimola Mill ethanolic seed extract on Acute Myeloid Leukemia [...] Read more.

Annona cherimola Mill is a large green fruit with black seeds widely known to possess toxic properties due to the presence of Annonaceous acetogenins. The present study investigates the anti-cancer properties of an Annona cherimola Mill ethanolic seed extract on Acute Myeloid Leukemia (AML) cell lines in vitro and elucidates the underlying cellular mechanism. The anti-proliferative effects of the extract on various AML cell lines and normal mesenchymal cells (MSCs) were assessed using WST-1 viability reagent. The pro-apoptotic effect of the extract was evaluated using Annexin V/PI staining and Cell Death ELISA. The underlying mechanism was deciphered by analyzing the expression of various proteins using western blots. Treatment with an A. cherimola seed ethanolic extract promotes a dose- and time-dependent inhibition of the proliferation of various AML cell lines, but not MSCs. Positive Annexin V staining, as well as DNA fragmentation, confirm an increase in apoptotic cell death by upregulating the expression of pro-apoptotic proteins which control both intrinsic and extrinsic pathways of apoptosis. GC/MS analysis revealed the presence of phytosterols, in addition to other bioactive compounds. In conclusion, Annona cherimola Mill seed extract, previously known to possess a potent toxic activity, induces apoptosis in AML cell lines by the activation of both the extrinsic and the intrinsic pathways. Full article

(This article belongs to the Collection Toxic and Pharmacological Effect of Plant Toxins)

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17 pages, 4410 KiB

Open AccessEditor’s ChoiceArticle

Fusarubin and Anhydrofusarubin Isolated from A Cladosporium Species Inhibit Cell Growth in Human Cancer Cell Lines

by Sabrina Adorisio, Alessandra Fierabracci, Isabella Muscari, Anna Marina Liberati, Lorenza Cannarile, Trinh Thi Thuy, Tran Van Sung, Hossain Sohrab, Choudhury Mahmood Hasan, Emira Ayroldi, Carlo Riccardi, Abdul Mazid and Domenico V. Delfino

Toxins 2019, 11(9), 503; https://doi.org/10.3390/toxins11090503 - 29 Aug 2019

Cited by 32 | Viewed by 5114

Abstract

Cladosporium species are endophytic fungi that grow on organic matter and are considered food contaminants. The anti-microbial and anti-tumor naphthoquinones fusarubin (FUS) and anhydrofusarubin (AFU) were isolated using column chromatography from a Cladosporium species residing inside Rauwolfia leaves. The impact of FUS and [...] Read more.

Cladosporium species are endophytic fungi that grow on organic matter and are considered food contaminants. The anti-microbial and anti-tumor naphthoquinones fusarubin (FUS) and anhydrofusarubin (AFU) were isolated using column chromatography from a Cladosporium species residing inside Rauwolfia leaves. The impact of FUS and AFU on cell growth was assessed in acute myeloid leukemia (OCI-AML3) and other hematologic tumor cell lines (HL-60, U937, and Jurkat). Treatment with FUS or AFU reduced the number of OCI-AML3 cells as evaluated by a hemocytometer. Flow cytometry analyses showed that this effect was accompanied by diverse impairments in cell cycle progression. Specifically, FUS (20 or 10 μg/mL significantly decreased the percentage of cells in S phase and increased the percentage of cells in G2/M phase, whereas AFU increased the percentage of cells in G0/G1 phase (50 and 25 μg/mL) and decreased the percentage of cells in S (50 μg/mL) and G2/M (50 and 25 μg/mL) phases. Both substances significantly increased apoptosis at higher concentrations. The effects of FUS were more potent than those of AFU, with FUS up-regulating p21 expression in a p53-dependent manner, as detected by Western blot analyses, likely the consequence of decreased ERK phosphorylation and increased p38 expression (both of which increase p21 stability). FUS also decreased Akt phosphorylation and resulted in increased Fas ligand production and caspase-8/3-dependent apoptosis. These results suggest that FUS and AFU inhibit proliferation and increase apoptosis in cell lines derived from hematological cancers. Full article

(This article belongs to the Collection Toxic and Pharmacological Effect of Plant Toxins)

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20 pages, 1879 KiB

Open AccessEditor’s ChoiceArticle

Molecular Characterisation of Aflatoxigenic and Non-Aflatoxigenic Strains of Aspergillus Section Flavi Isolated from Imported Peanuts along the Supply Chain in Malaysia

by Mahror Norlia, Selamat Jinap, Mahmud Ab Rashid Nor-Khaizura, Son Radu, Cheow Keat Chin, Nik Iskandar Putra Samsudin and Abdul Halim Farawahida

Toxins 2019, 11(9), 501; https://doi.org/10.3390/toxins11090501 - 29 Aug 2019

Cited by 21 | Viewed by 4799

Abstract

Peanuts are widely consumed in many local dishes in southeast Asian countries, especially in Malaysia which is one of the major peanut-importing countries in this region. Therefore, Aspergillus spp. and aflatoxin contamination in peanuts during storage are becoming major concerns due to the [...] Read more.

Peanuts are widely consumed in many local dishes in southeast Asian countries, especially in Malaysia which is one of the major peanut-importing countries in this region. Therefore, Aspergillus spp. and aflatoxin contamination in peanuts during storage are becoming major concerns due to the tropical weather in this region that favours the growth of aflatoxigenic fungi. The present study thus aimed to molecularly identify and characterise the Aspergillus section Flavi isolated from imported peanuts in Malaysia. The internal transcribed spacer (ITS) and β-tubulin sequences were used to confirm the species and determine the phylogenetic relationship among the isolates, while aflatoxin biosynthesis genes (aflR, aflP (omtA), aflD (nor-1), aflM (ver-1), and pksA) were targeted in a multiplex PCR to determine the toxigenic potential. A total of 76 and one isolates were confirmed as A. flavus and A. tamarii, respectively. The Maximum Likelihood (ML) phylogenetic tree resolved the species into two different clades in which all A. flavus (both aflatoxigenic and non-aflatoxigenic) were grouped in the same clade and A. tamarii was grouped in a different clade. The aflatoxin biosynthesis genes were detected in all aflatoxigenic A. flavus while the non-aflatoxigenic A. flavus failed to amplify at least one of the genes. The results indicated that both aflatoxigenic and non-aflatoxigenic A. flavus could survive in imported peanuts and, thus, appropriate storage conditions preferably with low temperature should be considered to avoid the re-emergence of aflatoxigenic A. flavus and the subsequent aflatoxin production in peanuts during storage. Full article

(This article belongs to the Special Issue Fungal Growth and Mycotoxins: Challenges for developing countries)

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13 pages, 848 KiB

Open AccessEditor’s ChoiceReview

Genetics, Toxicity, and Distribution of Enterohemorrhagic Escherichia coli Hemolysin

by Maike Schwidder, Laura Heinisch and Herbert Schmidt

Toxins 2019, 11(9), 502; https://doi.org/10.3390/toxins11090502 - 29 Aug 2019

Cited by 32 | Viewed by 7485

Abstract

The ability to produce enterohemolysin is regarded as a potential virulence factor for enterohemorrhagic Escherichia coli (EHEC) and is frequently associated with severe human diseases such as hemorrhagic colitis (HC) and the hemolytic uremic syndrome (HUS). The responsible toxin, which has also been [...] Read more.

The ability to produce enterohemolysin is regarded as a potential virulence factor for enterohemorrhagic Escherichia coli (EHEC) and is frequently associated with severe human diseases such as hemorrhagic colitis (HC) and the hemolytic uremic syndrome (HUS). The responsible toxin, which has also been termed EHEC-hemolysin (EHEC-Hly, syn. Ehx), belongs to the Repeats in Toxin (RTX)-family of pore-forming cytolysins and is characterized by the formation of incomplete turbid lysis zones on blood agar plates containing defibrinated sheep erythrocytes. Besides the expression of Shiga toxins (Stx) and the locus of enterocyte effacement (LEE), EHEC-Hly is a commonly used marker for the detection of potential pathogenic E. coli strains, although its exact role in pathogenesis is not completely understood. Based on the current knowledge of EHEC-Hly, this review describes the influence of various regulator proteins, explains the different mechanisms leading to damage of target cells, discusses the diagnostic role, and gives an insight of the prevalence and genetic evolution of the toxin. Full article

(This article belongs to the Special Issue RTX Toxins)

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14 pages, 1443 KiB

Open AccessEditor’s ChoiceArticle

Distribution of Toxinogenic Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus from Different Ecological Niches in Algeria

by Assia Mairi, Abdelaziz Touati, Alix Pantel, Karima Zenati, Alex Yahiaoui Martinez, Catherine Dunyach-Remy, Albert Sotto and Jean-Philippe Lavigne

Toxins 2019, 11(9), 500; https://doi.org/10.3390/toxins11090500 - 28 Aug 2019

Cited by 22 | Viewed by 4020

Abstract

The diffusion of Panton–Valentine leukocidin (PVL)–positive methicillin-resistant S. aureus (MRSA) is a health problem in Algeria. The objectives of the study were to investigate the global distribution of methicillin-susceptible S. aureus (MSSA) and MRSA isolates in different ecological niches in this country. In [...] Read more.

The diffusion of Panton–Valentine leukocidin (PVL)–positive methicillin-resistant S. aureus (MRSA) is a health problem in Algeria. The objectives of the study were to investigate the global distribution of methicillin-susceptible S. aureus (MSSA) and MRSA isolates in different ecological niches in this country. In total, 2246 samples were collected from humans, livestock, wild animals, pets, food products and the aquatic environment, from 12 Algerian provinces. A total of 312 S. aureus were detected from 2446 samples (12.7%) in the screened niches. We observed the emergence of toxinogenic S. aureus representing 41% of the isolates. Among them, we noted the diffusion of ST80-IV CA-MRSA PVL + strains isolated in human, animals, and food and genetic diversity of MSSA PVL + isolates. This study suggests an alarming dissemination of MRSA-ST80 PVL + in both human and extra-human sources in Algeria. Moreover, MSSA may become a permanent reservoir of the PVL genes necessary for human infections. Full article

(This article belongs to the Special Issue Methicillin-Resistant Staphylococci and Macrococci at the Interface of Human and Animal Health)

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18 pages, 3367 KiB

Open AccessEditor’s ChoiceArticle

Insights into the Diversity of Secondary Metabolites of Planktothrix Using a Biphasic Approach Combining Global Genomics and Metabolomics

by Sandra Kim Tiam, Muriel Gugger, Justine Demay, Séverine Le Manach, Charlotte Duval, Cécile Bernard and Benjamin Marie

Toxins 2019, 11(9), 498; https://doi.org/10.3390/toxins11090498 - 27 Aug 2019

Cited by 24 | Viewed by 5269

Abstract

Cyanobacteria are an ancient lineage of slow-growing photosynthetic bacteria and a prolific source of natural products with diverse chemical structures and potent biological activities and toxicities. The chemical identification of these compounds remains a major bottleneck. Strategies that can prioritize the most prolific [...] Read more.

Cyanobacteria are an ancient lineage of slow-growing photosynthetic bacteria and a prolific source of natural products with diverse chemical structures and potent biological activities and toxicities. The chemical identification of these compounds remains a major bottleneck. Strategies that can prioritize the most prolific strains and novel compounds are of great interest. Here, we combine chemical analysis and genomics to investigate the chemodiversity of secondary metabolites based on their pattern of distribution within some cyanobacteria. Planktothrix being a cyanobacterial genus known to form blooms worldwide and to produce a broad spectrum of toxins and other bioactive compounds, we applied this combined approach on four closely related strains of Planktothrix. The chemical diversity of the metabolites produced by the four strains was evaluated using an untargeted metabolomics strategy with high-resolution LC–MS. Metabolite profiles were correlated with the potential of metabolite production identified by genomics for the different strains. Although, the Planktothrix strains present a global similarity in terms of a biosynthetic cluster gene for microcystin, aeruginosin, and prenylagaramide for example, we found remarkable strain-specific chemodiversity. Only few of the chemical features were common to the four studied strains. Additionally, the MS/MS data were analyzed using Global Natural Products Social Molecular Networking (GNPS) to identify molecular families of the same biosynthetic origin. In conclusion, we depict an efficient, integrative strategy for elucidating the chemical diversity of a given genus and link the data obtained from analytical chemistry to biosynthetic genes of cyanobacteria. Full article

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12 pages, 1711 KiB

Open AccessEditor’s ChoiceArticle

A Novel Magnetic Molecular Imprinted Polymer for Selective Extraction of Zearalenone from Cereal Flours before Liquid Chromatography-Tandem Mass Spectrometry Determination

by Chiara Cavaliere, Michela Antonelli, Andrea Cerrato, Giorgia La Barbera, Aldo Laganà, Michele Laus, Susy Piovesana and Anna Laura Capriotti

Toxins 2019, 11(9), 493; https://doi.org/10.3390/toxins11090493 - 27 Aug 2019

Cited by 17 | Viewed by 3901

Abstract

Zearalenone (ZEN) is a nonsteroidal estrogenic mycotoxin produced by various Fusarium species and commonly occurring in corn and other cereals. Even though its acute toxicity is low, still the estrogenic activity of ZEN and metabolites is a matter of concern. In this work, [...] Read more.

Zearalenone (ZEN) is a nonsteroidal estrogenic mycotoxin produced by various Fusarium species and commonly occurring in corn and other cereals. Even though its acute toxicity is low, still the estrogenic activity of ZEN and metabolites is a matter of concern. In this work, a new magnetic molecularly imprinted polymer (mMIP) for the selective extraction of ZEN from cereal flours is presented. The mMIP was synthesized previously using quercetin as dummy template, and here we wanted to test its applicability to complex food samples. Analyte determination was carried out by high-performance liquid chromatography coupled to tandem mass spectrometry. The selectivity of the mMIP and the main validation method parameters were assessed. In particular, even in samples as complex as cereals, matrix effect was negligible. Although the mMIP showed cross-selectivity towards both ZEN-related and quercetin-related compounds, nonetheless ZEN recovery was > 95% for the two lower spiking levels, and the quantification limit was 0.14 ng g⁻¹, i.e., ca. 500 times lower than the maximum limit fixed for most cereals by European law. Therefore, the material, also in comparison with a commercial sorbent, appears suitable for the application in food analysis, also to isolate ZEN at trace levels. Full article

(This article belongs to the Special Issue Advanced Methods for Mycotoxins Detection)

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16 pages, 2485 KiB

Open AccessEditor’s ChoiceArticle

Influence of Two Garlic-Derived Compounds, Propyl Propane Thiosulfonate (PTS) and Propyl Propane Thiosulfinate (PTSO), on Growth and Mycotoxin Production by Fusarium Species In Vitro and in Stored Cereals

by Kalliopi Mylona, Esther Garcia-Cela, Michael Sulyok, Angel Medina and Naresh Magan

Toxins 2019, 11(9), 495; https://doi.org/10.3390/toxins11090495 - 27 Aug 2019

Cited by 24 | Viewed by 4902

Abstract

Two garlic-derived compounds, Propyl Propane Thiosulfonate (PTS) and Propyl Propane Thiosulfinate (PTSO), were examined for their efficacy against mycotoxigenic Fusarium species (F. graminearum, F. langsethiae, F. verticillioides). The objectives were to assess the inhibitory effect of these compounds on [...] Read more.

Two garlic-derived compounds, Propyl Propane Thiosulfonate (PTS) and Propyl Propane Thiosulfinate (PTSO), were examined for their efficacy against mycotoxigenic Fusarium species (F. graminearum, F. langsethiae, F. verticillioides). The objectives were to assess the inhibitory effect of these compounds on growth and mycotoxin production in vitro, and in situ in artificially inoculated wheat, oats and maize with one isolate of each respectively, at different water activity (a_w) conditions when stored for up to 20 days at 25 °C. In vitro, 200 ppm of either PTS or PTSO reduced fungal growth by 50–100% and mycotoxin production by >90% depending on species, mycotoxin and a_w conditions on milled wheat, oats and maize respectively. PTS was generally more effective than PTSO. Deoxynivalenol (DON) and zearalenone (ZEN) were decreased by 50% with 80 ppm PTSO. One-hundred ppm of PTS reduced DON and ZEN production in wheat stored at 0.93 a_w for 20 days, although contamination was still above the legislative limits. Contrasting effects on T-2/HT-2 toxin contamination of oats was found depending on a_w, with PTS stimulating production under marginal conditions (0.93 a_w), but at 0.95 a_w effective control was achieved with 100 ppm. Treatment of stored maize inoculated with F. verticilliodies resulted in a stimulation of total fumonsins in most treatments. The potential use of such compounds for mycotoxin control in stored commodities is discussed. Full article

(This article belongs to the Special Issue Novel Approaches to Minimising Mycotoxin Contamination)

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21 pages, 6496 KiB

Open AccessEditor’s ChoiceArticle

Venomic, Transcriptomic, and Bioactivity Analyses of Pamphobeteus verdolaga Venom Reveal Complex Disulfide-Rich Peptides That Modulate Calcium Channels

by Sebastian Estrada-Gomez, Fernanda Caldas Cardoso, Leidy Johana Vargas-Muñoz, Juan Carlos Quintana-Castillo, Claudia Marcela Arenas Gómez, Sandy Steffany Pineda and Monica Maria Saldarriaga-Cordoba

Toxins 2019, 11(9), 496; https://doi.org/10.3390/toxins11090496 - 27 Aug 2019

Cited by 16 | Viewed by 4791

Abstract

Pamphobeteus verdolaga is a recently described Theraphosidae spider from the Andean region of Colombia. Previous reports partially characterized its venom profile. In this study, we conducted a detailed analysis that includes reversed-phase high-performance liquid chromatography (rp-HPLC), calcium influx assays, tandem mass spectrometry analysis [...] Read more.

Pamphobeteus verdolaga is a recently described Theraphosidae spider from the Andean region of Colombia. Previous reports partially characterized its venom profile. In this study, we conducted a detailed analysis that includes reversed-phase high-performance liquid chromatography (rp-HPLC), calcium influx assays, tandem mass spectrometry analysis (tMS/MS), and venom-gland transcriptome. rp-HPLC fractions of P. verdolaga venom showed activity on Ca_V2.2, Ca_V3.2, and Na_V1.7 ion channels. Active fractions contained several peptides with molecular masses ranging from 3399.4 to 3839.6 Da. The tMS/MS analysis of active fraction displaying the strongest activity to inhibit calcium channels showed sequence fragments similar to one of the translated transcripts detected in the venom-gland transcriptome. The putative peptide of this translated transcript corresponded to a toxin, here named ω-theraphositoxin-Pv3a, a potential ion channel modulator toxin that is, in addition, very similar to other theraphositoxins affecting calcium channels (i.e., ω-theraphotoxin-Asp1a). Additionally, using this holistic approach, we found that P. verdolaga venom is an important source of disulfide-rich proteins expressing at least eight superfamilies. Full article

(This article belongs to the Special Issue Venoms and Ion Channels)

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21 pages, 1055 KiB

Open AccessEditor’s ChoiceReview

Aggregatibacter actinomycetemcomitans Leukotoxin (LtxA; Leukothera^®): Mechanisms of Action and Therapeutic Applications

by Brian A. Vega, Benjamin A. Belinka Jr. and Scott C. Kachlany

Toxins 2019, 11(9), 489; https://doi.org/10.3390/toxins11090489 - 26 Aug 2019

Cited by 26 | Viewed by 5897

Abstract

Aggregatibacter actinomycetemcomitans is an oral pathogen that produces the RTX toxin, leukotoxin (LtxA; Leukothera^®). A. actinomycetemcomitans is strongly associated with the development of localized aggressive periodontitis. LtxA acts as a virulence factor for A. actinomycetemcomitans to subvert the host immune response [...] Read more.

Aggregatibacter actinomycetemcomitans is an oral pathogen that produces the RTX toxin, leukotoxin (LtxA; Leukothera^®). A. actinomycetemcomitans is strongly associated with the development of localized aggressive periodontitis. LtxA acts as a virulence factor for A. actinomycetemcomitans to subvert the host immune response by binding to the β₂ integrin lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18) on white blood cells (WBCs), causing cell death. In this paper, we reviewed the state of knowledge on LtxA interaction with WBCs and the subsequent mechanisms of induced cell death. Finally, we touched on the potential therapeutic applications of LtxA (trade name Leukothera^®) toxin therapy for the treatment of hematological malignancies and immune-mediated diseases. Full article

(This article belongs to the Special Issue RTX Toxins)

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11 pages, 1951 KiB

Open AccessEditor’s ChoiceArticle

TMA, A Forgotten Uremic Toxin, but Not TMAO, Is Involved in Cardiovascular Pathology

by Kinga Jaworska, Dagmara Hering, Grażyna Mosieniak, Anna Bielak-Zmijewska, Marta Pilz, Michał Konwerski, Aleksandra Gasecka, Agnieszka Kapłon-Cieślicka, Krzysztof Filipiak, Ewa Sikora, Robert Hołyst and Marcin Ufnal

Toxins 2019, 11(9), 490; https://doi.org/10.3390/toxins11090490 - 26 Aug 2019

Cited by 80 | Viewed by 9628

Abstract

Trimethylamine-N-oxide (TMAO) has been suggested as a marker and mediator of cardiovascular diseases. However, data are contradictory, and the mechanisms are obscure. Strikingly, the role of the TMAO precursor trimethylamine (TMA) has not drawn attention in cardiovascular studies even though toxic effects of [...] Read more.

Trimethylamine-N-oxide (TMAO) has been suggested as a marker and mediator of cardiovascular diseases. However, data are contradictory, and the mechanisms are obscure. Strikingly, the role of the TMAO precursor trimethylamine (TMA) has not drawn attention in cardiovascular studies even though toxic effects of TMA were proposed several decades ago. We assessed plasma TMA and TMAO levels in healthy humans (HH) and cardiovascular patients qualified for aortic valve replacement (CP). The cytotoxicity of TMA and TMAO in rat cardiomyocytes was evaluated using an MTT test. The effects of TMA and TMAO on albumin and lactate dehydrogenase (LDH) were assessed using fluorescence correlation spectroscopy. In comparison to HH, CP had a two-fold higher plasma TMA (p < 0.001) and a trend towards higher plasma TMAO (p = 0.07). In CP plasma, TMA was inversely correlated with an estimated glomerular filtration rate (eGFR, p = 0.002). TMA but not TMAO reduced cardiomyocytes viability. Incubation with TMA but not TMAO resulted in the degradation of the protein structure of LDH and albumin. In conclusion, CP show increased plasma TMA, which is inversely correlated with eGFR. TMA but not TMAO exerts negative effects on cardiomyocytes, likely due to its disturbing effect on proteins. Therefore, TMA but not TMAO may be a toxin and a marker of cardiovascular risk. Full article

(This article belongs to the Section Uremic Toxins)

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22 pages, 2742 KiB

Open AccessEditor’s ChoiceReview

Immunogenicity Associated with Botulinum Toxin Treatment

by Steven Bellows and Joseph Jankovic

Toxins 2019, 11(9), 491; https://doi.org/10.3390/toxins11090491 - 26 Aug 2019

Cited by 112 | Viewed by 12657

Abstract

Botulinum toxin (BoNT) has been used for the treatment of a variety of neurologic, medical and cosmetic conditions. Two serotypes, type A (BoNT-A) and type B (BoNT-B), are currently in clinical use. While considered safe and effective, their use has been rarely complicated [...] Read more.

Botulinum toxin (BoNT) has been used for the treatment of a variety of neurologic, medical and cosmetic conditions. Two serotypes, type A (BoNT-A) and type B (BoNT-B), are currently in clinical use. While considered safe and effective, their use has been rarely complicated by the development of antibodies that reduce or negate their therapeutic effect. The presence of antibodies has been attributed to shorter dosing intervals (and booster injections), higher doses per injection cycle, and higher amounts of antigenic protein. Other factors contributing to the immunogenicity of BoNT include properties of each serotype, such as formulation, manufacturing, and storage of the toxin. Some newer formulations with purified core neurotoxin devoid of accessory proteins may have lower overall immunogenicity. Several assays are available for the detection of antibodies, including both structural assays such as ELISA and mouse-based bioassays, but there is no consistent correlation between these antibodies and clinical response. Prevention and treatment of antibody-associated non-responsiveness is challenging and primarily involves the use of less immunogenic formulations of BoNT, waiting for the spontaneous disappearance of the neutralizing antibody, and switching to an immunologically alternate type of BoNT. Full article

(This article belongs to the Special Issue Characterization and Quantitative Analysis of Botulinum Neurotoxin)

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19 pages, 1184 KiB

Open AccessEditor’s ChoiceArticle

Cytotoxic and Proapoptotic Activity of Sanguinarine, Berberine, and Extracts of Chelidonium majus L. and Berberis thunbergii DC. toward Hematopoietic Cancer Cell Lines

by Anna Och, Daniel Zalewski, Łukasz Komsta, Przemysław Kołodziej, Janusz Kocki and Anna Bogucka-Kocka

Toxins 2019, 11(9), 485; https://doi.org/10.3390/toxins11090485 - 23 Aug 2019

Cited by 42 | Viewed by 6316

Abstract

Isoquinoline alkaloids belong to the toxic secondary metabolites occurring in plants of many families. The high biological activity makes these compounds promising agents for use in medicine, particularly as anticancer drugs. The aim of our study was to evaluate the cytotoxicity and proapoptotic [...] Read more.

Isoquinoline alkaloids belong to the toxic secondary metabolites occurring in plants of many families. The high biological activity makes these compounds promising agents for use in medicine, particularly as anticancer drugs. The aim of our study was to evaluate the cytotoxicity and proapoptotic activity of sanguinarine, berberine, and extracts of Chelidonium majus L. and Berberis thunbergii DC. IC10, IC50, and IC90 doses were established toward hematopoietic cancer cell lines using trypan blue staining. Alterations in the expression of 18 apoptosis-related genes in cells exposed to IC10, IC50, and IC90 were evaluated using real-time PCR. Sanguinarine and Chelidonium majus L. extract exhibit significant cytotoxicity against all studied cell lines. Lower cytotoxic activity was demonstrated for berberine. Berberis thunbergii DC. extract had no influence on cell viability. Berberine, sanguinarine, and Chelidonium majus L. extract altered the expression of apoptosis-related genes in all tested cell lines, indicating the induction of apoptosis. The presented study confirmed the substantial cytotoxicity and proapoptotic activity of sanguinarine, berberine, and Chelidonium majus L. extract toward the studied hematopoietic cell lines, which indicates the utility of these substances in anticancer therapy. Full article

(This article belongs to the Special Issue Biological Activities of Alkaloids: From Toxicology to Pharmacology)

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22 pages, 10781 KiB

Open AccessEditor’s ChoiceArticle

Chronic Low Dose Oral Exposure to Microcystin-LR Exacerbates Hepatic Injury in a Murine Model of Non-Alcoholic Fatty Liver Disease

by Apurva Lad, Robin C. Su, Joshua D. Breidenbach, Paul M. Stemmer, Nicholas J. Carruthers, Nayeli K. Sanchez, Fatimah K. Khalaf, Shungang Zhang, Andrew L. Kleinhenz, Prabhatchandra Dube, Chrysan J. Mohammed, Judy A. Westrick, Erin L. Crawford, Dilrukshika Palagama, David Baliu-Rodriguez, Dragan Isailovic, Bruce Levison, Nikolai Modyanov, Amira F. Gohara, Deepak Malhotra, Steven T. Haller and David J. Kennedy Show full author list Hide full author list

Toxins 2019, 11(9), 486; https://doi.org/10.3390/toxins11090486 - 23 Aug 2019

Cited by 36 | Viewed by 7475

Abstract

Microcystins are potent hepatotoxins that have become a global health concern in recent years. Their actions in at-risk populations with pre-existing liver disease is unknown. We tested the hypothesis that the No Observed Adverse Effect Level (NOAEL) of Microcystin-LR (MC-LR) established in healthy [...] Read more.

Microcystins are potent hepatotoxins that have become a global health concern in recent years. Their actions in at-risk populations with pre-existing liver disease is unknown. We tested the hypothesis that the No Observed Adverse Effect Level (NOAEL) of Microcystin-LR (MC-LR) established in healthy mice would cause exacerbation of hepatic injury in a murine model (Lepr^db/J) of Non-alcoholic Fatty Liver Disease (NAFLD). Ten-week-old male Lepr^db/J mice were gavaged with 50 μg/kg, 100 μg/kg MC-LR or vehicle every 48 h for 4 weeks (n = 15–17 mice/group). Early mortality was observed in both the 50 μg/kg (1/17, 6%), and 100 μg/kg (3/17, 18%) MC-LR exposed mice. MC-LR exposure resulted in significant increases in circulating alkaline phosphatase levels, and histopathological markers of hepatic injury as well as significant upregulation of genes associated with hepatotoxicity, necrosis, nongenotoxic hepatocarcinogenicity and oxidative stress response. In addition, we observed exposure dependent changes in protein phosphorylation sites in pathways involved in inflammation, immune function, and response to oxidative stress. These results demonstrate that exposure to MC-LR at levels that are below the NOAEL established in healthy animals results in significant exacerbation of hepatic injury that is accompanied by genetic and phosphoproteomic dysregulation in key signaling pathways in the livers of NAFLD mice. Full article

(This article belongs to the Special Issue Freshwater Algal Toxins: Monitoring and Toxicity Profile)

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12 pages, 1446 KiB

Open AccessEditor’s ChoiceArticle

Effects of Microcystin-LR on the Microstructure and Inflammation-Related Factors of Jejunum in Mice

by Linghui Cao, Feiyu Huang, Isaac Yaw Massey, Cong Wen, Shuilin Zheng, Shuaishuai Xu and Fei Yang

Toxins 2019, 11(9), 482; https://doi.org/10.3390/toxins11090482 - 21 Aug 2019

Cited by 51 | Viewed by 4157

Abstract

The increasing cyanobacterial blooms have recently been considered a severe environmental problem. Microcystin-leucine arginine (MC-LR) is one of the secondary products of cyanobacteria metabolism and most harmful cyanotoxins found in water bodies. Studies show MC-LR negatively affects various human organs when exposed to [...] Read more.

The increasing cyanobacterial blooms have recently been considered a severe environmental problem. Microcystin-leucine arginine (MC-LR) is one of the secondary products of cyanobacteria metabolism and most harmful cyanotoxins found in water bodies. Studies show MC-LR negatively affects various human organs when exposed to it. The phenotype of the jejunal chronic toxicity induced by MC-LR has not been well described. The aim of this paper was to investigate the effects of MC-LR on the jejunal microstructure and expression level of inflammatory-related factors in jejunum. Mice were treated with different doses (1, 30, 60, 90 and 120 μg/L) of MC-LR for six months. The microstructure and mRNA expression levels of inflammation-related factors in jejunum were analyzed. Results showed that the microstructure of the jejunum was destroyed and expression levels of inflammation-related factors interleukin (IL)-1β, interleukin (IL)-8, tumor necrosis factor alpha, transforming growth factor-β1 and interleukin (IL)-10 were altered at different MC-LR concentrations. To the best of our knowledge, this is the first study that mice were exposed to a high dose of MC-LR for six months. Our data demonstrated MC-LR had the potential to cause intestinal toxicity by destroying the microstructure of the jejunum and inducing an inflammatory response in mice, which provided new insight into understanding the prevention and diagnosis of the intestinal diseases caused by MC-LR. Full article

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21 pages, 2157 KiB

Open AccessEditor’s ChoiceArticle

Biotransformation of the Mycotoxin Zearalenone to its Metabolites Hydrolyzed Zearalenone (HZEN) and Decarboxylated Hydrolyzed Zearalenone (DHZEN) Diminishes its Estrogenicity In Vitro and In Vivo

by Sebastian Fruhauf, Barbara Novak, Veronika Nagl, Matthias Hackl, Doris Hartinger, Valentina Rainer, Silvia Labudová, Gerhard Adam, Markus Aleschko, Wulf-Dieter Moll, Michaela Thamhesl and Bertrand Grenier

Toxins 2019, 11(8), 481; https://doi.org/10.3390/toxins11080481 - 20 Aug 2019

Cited by 41 | Viewed by 5473

Abstract

Zearalenone (ZEN)-degrading enzymes are a promising strategy to counteract the negative effects of this mycotoxin in livestock. The reaction products of such enzymes need to be thoroughly characterized before technological application as a feed additive can be envisaged. Here, we evaluated the estrogenic [...] Read more.

Zearalenone (ZEN)-degrading enzymes are a promising strategy to counteract the negative effects of this mycotoxin in livestock. The reaction products of such enzymes need to be thoroughly characterized before technological application as a feed additive can be envisaged. Here, we evaluated the estrogenic activity of the metabolites hydrolyzed zearalenone (HZEN) and decarboxylated hydrolyzed zearalenone (DHZEN) formed by hydrolysis of ZEN by the zearalenone-lactonase Zhd101p. ZEN, HZEN, and DHZEN were tested in two in vitro models, the MCF-7 cell proliferation assay (0.01–500 nM) and an estrogen-sensitive yeast bioassay (1–10,000 nM). In addition, we compared the impact of dietary ZEN (4.58 mg/kg) and equimolar dietary concentrations of HZEN and DHZEN on reproductive tract morphology as well as uterine mRNA and microRNA expression in female piglets (n = 6, four weeks exposure). While ZEN increased cell proliferation and reporter gene transcription, neither HZEN nor DHZEN elicited an estrogenic response, suggesting that these metabolites are at least 50–10,000 times less estrogenic than ZEN in vitro. In piglets, HZEN and DHZEN did not increase vulva size or uterus weight. Moreover, RNA transcripts altered upon ZEN treatment (EBAG9, miR-135a-5p, miR-187-3p and miR-204-5p) were unaffected by HZEN and DHZEN. Our study shows that both metabolites exhibit markedly reduced estrogenicity in vitro and in vivo, and thus provides an important basis for further evaluation of ZEN-degrading enzymes. Full article

(This article belongs to the Special Issue Novel Approaches to Minimising Mycotoxin Contamination)

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17 pages, 2310 KiB

Open AccessEditor’s ChoiceArticle

Bacteriocin Occurrence and Activity in Escherichia coli Isolated from Bovines and Wastewater

by Andrew Cameron, Rahat Zaheer, Emelia H. Adator, Ruth Barbieri, Tim Reuter and Tim A. McAllister

Toxins 2019, 11(8), 475; https://doi.org/10.3390/toxins11080475 - 15 Aug 2019

Cited by 31 | Viewed by 5640

Abstract

The increasing prevalence of antimicrobial resistant (AMR) E. coli and related Enterobacteriaceae is a serious problem necessitating new mitigation strategies and antimicrobial agents. Bacteriocins, functionally diverse toxins produced by most microbes, have long been studied for their antimicrobial potential. Bacteriocins have once again [...] Read more.

The increasing prevalence of antimicrobial resistant (AMR) E. coli and related Enterobacteriaceae is a serious problem necessitating new mitigation strategies and antimicrobial agents. Bacteriocins, functionally diverse toxins produced by most microbes, have long been studied for their antimicrobial potential. Bacteriocins have once again received attention for their role as probiotic traits that could mitigate pathogen burden and AMR bacteria in livestock. Here, bacteriocins were identified by activity screening and whole-genome sequencing of bacteriocin-producers capable of inhibiting bovine and wastewater E. coli isolates enriched for resistance to cephalosporins. Producers were tested for activity against shiga toxin-producing E. coli (STEC), AMR E. coli, and related enteric pathogens. Multiple bacteriocins were found in 14 out of 90 E. coli isolates tested. Based on alignment within BACTIBASE, colicins M, B, R, Ia, Ib, S4, E1, E2, and microcins V, J25, and H47, encoded by identical, variant, or truncated genes were identified. Although some bacteriocin-producers exhibited activity against AMR and STEC E. coli in agar-based assays, most did not. Despite this idiosyncrasy, liquid co-cultures of all bacteriocinogenic isolates with luciferase-expressing generic (K12) or STEC E. coli (EDL933) resulted in inhibited growth or reduced viability. These abundant toxins may have real potential as next-generation control strategies in livestock production systems but separating the bacteriocin from its immunity gene may be necessary for such a strategy to be effective. Full article

(This article belongs to the Special Issue Molecular Basis and the Pathogenesis of Enterohemorrhagic Escherichia coli Infections)

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13 pages, 2613 KiB

Open AccessEditor’s ChoiceArticle

Structure Elucidation and Toxicity Analysis of the Degradation Products of Deoxynivalenol by Gaseous Ozone

by Mengmeng Li, Erqi Guan and Ke Bian

Toxins 2019, 11(8), 474; https://doi.org/10.3390/toxins11080474 - 15 Aug 2019

Cited by 27 | Viewed by 4177

Abstract

Fusarium Head Blight (FHB) or scab is a fungal disease of cereal grains. Wheat scab affects the yield and quality of wheat and produces mycotoxins such as deoxynivalenol (DON), which can seriously threaten human and animal health. In this study, gaseous ozone was [...] Read more.

Fusarium Head Blight (FHB) or scab is a fungal disease of cereal grains. Wheat scab affects the yield and quality of wheat and produces mycotoxins such as deoxynivalenol (DON), which can seriously threaten human and animal health. In this study, gaseous ozone was used to degrade DON in wheat scab and the degradation products of ozonolysis were analyzed by ultra-performance liquid chromatography quadrupole-orbitrap mass spectrometry (UHPLC Q-Orbitrap). Toxicology analyses of the degradation products were also studied using structure-activity relationships. Ozone (8 mg L⁻¹ concentration) was applied to 2 μg mL⁻¹ of DON in ultrapure water, resulted in 95.68% degradation within 15 s. Ten ozonized products of DON in ultrapure water were analyzed and six main products (C₁₅H₁₈O₇, C₁₅H₁₈O₉, C₁₅H₂₂O₉, C₁₅H₂₀O₁₀, C₁₅H₁₈O_8, and C₁₅H₂₀O₉) were analyzed at varying concentrations of ozone and DON. Structural formulae were assigned to fragmentation products generated by MS² and Mass Frontier^® software. According to structure-activity relationship studies, the toxicities of the ozonized products were significantly decreased due to de-epoxidation and the attack of ozone at the C_9-10 double bond in DON. Based on the results of the study above, we can find that gaseous ozone is an efficient and safe technology to degrade DON, and these results may provide a theoretical basis for the practical research of detoxifying DON in scabby wheat and other grains. Full article

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14 pages, 1829 KiB

Open AccessEditor’s ChoiceCommunication

Clostridium botulinum and Clostridium perfringens Occurrence in Kazakh Honey Samples

by Balgabay Maikanov, Raikhan Mustafina, Laura Auteleyeva, Jan Wiśniewski, Krzysztof Anusz, Tomasz Grenda, Krzysztof Kwiatek, Magdalena Goldsztejn and Magdalena Grabczak

Toxins 2019, 11(8), 472; https://doi.org/10.3390/toxins11080472 - 13 Aug 2019

Cited by 25 | Viewed by 7758

Abstract

The aim of this study was to assess occurrence of Clostridium botulinum and Clostridium perfringens in honey samples from Kazakhstan. Analyses were carried out using a set of PCR methods for identification of anaerobic bacteria, and detection of toxin genes of C. botulinum [...] Read more.

The aim of this study was to assess occurrence of Clostridium botulinum and Clostridium perfringens in honey samples from Kazakhstan. Analyses were carried out using a set of PCR methods for identification of anaerobic bacteria, and detection of toxin genes of C. botulinum and C. perfringens. Among 197 samples, C. botulinum was noticed in only one (0.5%). The isolated strain of this pathogen showed the presence of the bont/A and ntnh genes. C. perfringens strains were isolated from 18 (9%) samples, and mPCR (multiplex PCR) analysis led to them all being classified as toxin type A with the ability to produce α toxin. Sequence analysis of 16S rDNA genes showed occurrence in 4 samples of other anaerobes related to C. botulinum, which were C. sporogenes and C. beijerinckii strains. C. botulinum prevalence in honey samples from Kazakhstan in comparison to the prevalence in samples collected from the other regions seems to be less. The highest prevalence of Clostridium sp. was noticed in the East Kazakhstan province. Our study is the first survey on BoNT-producing clostridia and C. perfringens prevalence in Kazakh honey. Full article

(This article belongs to the Special Issue New Challenges in Foodborne Botulism Outbreaks)

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12 pages, 286 KiB

Open AccessEditor’s ChoiceArticle

Determination of Ochratoxin A (OTA), Ochratoxin B (OTB), T-2, and HT-2 Toxins in Wheat Grains, Wheat Flour, and Bread in Lebanon by LC-MS/MS

by Jomana Elaridi, Osama Yamani, Amira Al Matari, Saada Dakroub and Zouhair Attieh

Toxins 2019, 11(8), 471; https://doi.org/10.3390/toxins11080471 - 12 Aug 2019

Cited by 36 | Viewed by 4786

Abstract

Cereals are prone to fungal infection during growth, harvesting, transportation, and/or storage. As a result, cereals such as wheat grains and wheat-derived products may be contaminated with mycotoxins leading to acute and chronic health exposure. The current study investigated the presence of the [...] Read more.

Cereals are prone to fungal infection during growth, harvesting, transportation, and/or storage. As a result, cereals such as wheat grains and wheat-derived products may be contaminated with mycotoxins leading to acute and chronic health exposure. The current study investigated the presence of the mycotoxins: ochratoxin A (OTA), ochratoxin B (OTB), T-2, and HT-2 toxins in samples of wheat grains (n = 50), wheat flour (n = 50), and bread (n = 37) from the main mills in Lebanon using LC-MS/MS. Accuracy ranged from 98–100%, recoveries from 93–105%, and intraday and interday precision were 5–7% and 9–12%, respectively. The tested wheat grains, wheat flour, and bread samples did not contain detectable levels of T-2 and HT-2 toxins and OTB. Four wheat flour samples (8% of flour samples) showed positive OTA levels ranging from 0.6–3.4 μg·kg⁻¹ with an arithmetic mean of 1.9 ± 0.2 μg·kg⁻¹. Only one sample contained an OTA concentration greater than the limit set by the European Union (3 μg·kg⁻¹) for wheat-derived products. This study suggests that mycotoxin contamination of wheat grains, wheat flour, and bread in Lebanon is currently not a serious public health concern. However, surveillance strategies and monitoring programs must be routinely implemented to ensure minimal mycotoxin contamination of wheat-based products. Full article

(This article belongs to the Section Mycotoxins)

11 pages, 828 KiB

Open AccessEditor’s ChoiceArticle

Contrasting Toxin Selectivity between the Marine Pufferfish Takifugu pardalis and the Freshwater Pufferfish Pao suvattii

by Wei Gao, Yoko Kanahara, Misako Yamada, Ryohei Tatsuno, Hiroyuki Yoshikawa, Hiroyuki Doi, Tomohiro Takatani and Osamu Arakawa

Toxins 2019, 11(8), 470; https://doi.org/10.3390/toxins11080470 - 10 Aug 2019

Cited by 28 | Viewed by 4388

Abstract

To clarify the differences in toxin selectivity between marine and freshwater pufferfish, we conducted experiments in artificially reared nontoxic specimens of Takifugu pardalis (marine) and Pao suvattii (freshwater) using tetrodotoxin (TTX) and paralytic shellfish poison (PSP; decarbamoylsaxitoxin (dcSTX) or saxitoxin (STX)). T. pardalis [...] Read more.

To clarify the differences in toxin selectivity between marine and freshwater pufferfish, we conducted experiments in artificially reared nontoxic specimens of Takifugu pardalis (marine) and Pao suvattii (freshwater) using tetrodotoxin (TTX) and paralytic shellfish poison (PSP; decarbamoylsaxitoxin (dcSTX) or saxitoxin (STX)). T. pardalis specimens were administered feed homogenate containing TTX or dcSTX (dose of toxin, 55.2 nmol/fish) and P. suvattii specimens were administered feed homogenate containing TTX + STX (dose of each toxin, 19.2 nmol/fish) by oral gavage. The toxin content in the intestine, muscle, skin, liver, and gonads was quantified after 24 and 48 or 72 h. In T. pardalis, TTX administered into the intestine was absorbed into the body and transferred and retained mainly in the skin and liver, while dcSTX was hardly retained in the body, although it partly remained in the intestine. In strong contrast, in P. suvattii, little TTX remained in the body, whereas STX was absorbed into the body and was transferred and retained in the ovary and skin. The findings revealed that TTX/PSP selectivity differs between the marine species T. pardalis and the freshwater species P. suvattii. T. pardalis, which naturally harbors TTX, selectively accumulates TTX, and P. suvattii, which naturally harbors PSP, selectively accumulates PSP. Full article

(This article belongs to the Special Issue Isolation and Characterization of Marine Toxins)

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12 pages, 1933 KiB

Open AccessEditor’s ChoiceArticle

Aflatoxin Exposure from Milk in Rural Kenya and the Contribution to the Risk of Liver Cancer

by Anima J. Sirma, Kohei Makita, Delia Grace Randolph, Daniel Senerwa and Johanna F. Lindahl

Toxins 2019, 11(8), 469; https://doi.org/10.3390/toxins11080469 - 10 Aug 2019

Cited by 18 | Viewed by 5007

Abstract

Milk is an important commodity in Kenya; the country has the largest dairy herd and highest per capita milk consumption in East Africa. As such, hazards in milk are of concern. Aflatoxin M₁ (AFM₁) is a toxic metabolite of aflatoxin [...] Read more.

Milk is an important commodity in Kenya; the country has the largest dairy herd and highest per capita milk consumption in East Africa. As such, hazards in milk are of concern. Aflatoxin M₁ (AFM₁) is a toxic metabolite of aflatoxin B₁ (AFB₁) excreted in milk by lactating animals after ingesting AFB₁-contaminated feeds. This metabolite is injurious to human health, but there is little information on the risk to human health posed by AFM₁ in milk in rural Kenya. To fill this gap, a quantitative risk assessment (QRA) applying probabilistic statistical tools to quantify risks was conducted. This assessed the risk of liver cancer posed by AFM₁ in milk, assuming 10-fold lower carcinogenicity than AFB₁. Data from four agro–ecological zones in Kenya (semi-arid, temperate, sub-humid and humid) were used. We estimated that people were exposed to between 0.3 and 1 ng AFM₁ per kg body weight per day through the consumption of milk. The annual incidence rates of cancer attributed to the consumption of AFM₁ in milk were 3.5 × 10⁻³ (95% CI: 3 × 10⁻³–3.9 × 10⁻³), 2.9 × 10⁻³ (95% CI: 2.5 × 10⁻³–3.3 × 10⁻³), 1.4 × 10⁻³ (95% CI: 1.2 × 10⁻³–1.5 × 10⁻³) and 2.7 × 10⁻³ (95% CI: 2.3 × 10⁻³–3 × 10⁻³) cancers per 100,000 in adult females, adult males, children 6–18 years old, and in children less than five years old, respectively. Our results show that aflatoxin exposure from milk contributes relatively little to the incidence of liver cancer. Nonetheless, risk managers should take action based on cumulative exposure from all sources of aflatoxins. Full article

(This article belongs to the Special Issue Dietary Mycotoxin Exposure: Emerging Risks to Human Health)

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13 pages, 2488 KiB

Open AccessEditor’s ChoiceArticle

Paralytic Shellfish Toxin Uptake, Assimilation, Depuration, and Transformation in the Southeast Asian Green-Lipped Mussel (Perna viridis)

by John Kristoffer Andres, Aletta T. Yñiguez, Jennifer Mary Maister, Andrew D. Turner, Dave Eldon B. Olano, Jenelyn Mendoza, Lilibeth Salvador-Reyes and Rhodora V. Azanza

Toxins 2019, 11(8), 468; https://doi.org/10.3390/toxins11080468 - 9 Aug 2019

Cited by 23 | Viewed by 6984

Abstract

Bivalve molluscs represent an important food source within the Philippines, but the health of seafood consumers is compromised through the accumulation of harmful algal toxins in edible shellfish tissues. In order to assess the dynamics of toxin risk in shellfish, this study investigated [...] Read more.

Bivalve molluscs represent an important food source within the Philippines, but the health of seafood consumers is compromised through the accumulation of harmful algal toxins in edible shellfish tissues. In order to assess the dynamics of toxin risk in shellfish, this study investigated the uptake, depuration, assimilation, and analogue changes of paralytic shellfish toxins in Perna viridis. Tank experiments were conducted where mussels were fed with the toxic dinoflagellate Alexandrium minutum. Water and shellfish were sampled over a six day period to determine toxin concentrations in the shellfish meat and water, as well as algal cell densities. The maximum summed toxin concentration determined was 367 µg STX eq./100 g shellfish tissue, more than six times higher than the regulatory action limit in the Philippines. Several uptake and depuration cycles were observed during the study, with the first observed within the first 24 h coinciding with high algal cell densities. Toxin burdens were assessed within different parts of the shellfish tissue, with the highest levels quantified in the mantle during the first 18 h period but shifting towards the gut thereafter. A comparison of toxin profile data evidenced the conversion of GTX1,4 in the source algae to the less potent GTX2,3 in the shellfish tissue. Overall, the study illustrated the temporal variability in Perna viridis toxin concentrations during a modelled algal bloom event, and the accumulation of toxin from the water even after toxic algae were removed. Full article

(This article belongs to the Special Issue Marine Biotoxins and Seafood Poisoning)

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16 pages, 1711 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Biomonitoring of Deoxynivalenol and Deoxynivalenol-3-glucoside in Human Volunteers: Renal Excretion Profiles

by Marcel Mengelers, Marco Zeilmaker, Arnau Vidal, Marthe De Boevre, Sarah De Saeger and Rudolf Hoogenveen

Toxins 2019, 11(8), 466; https://doi.org/10.3390/toxins11080466 - 8 Aug 2019

Cited by 33 | Viewed by 4268

Abstract

Biomarkers for the determination of the dietary exposure to deoxynivalenol (DON) have been proposed in the past but so far no quantification of their use in humans has been carried out. Following a human intervention study with two mycotoxins, namely DON and deoxynivalenol-3-glucoside [...] Read more.

Biomarkers for the determination of the dietary exposure to deoxynivalenol (DON) have been proposed in the past but so far no quantification of their use in humans has been carried out. Following a human intervention study with two mycotoxins, namely DON and deoxynivalenol-3-glucoside (DON3G), the renal excretion of these compounds, including their phase II metabolites, was analysed. The purpose was to develop biokinetic models that can be used to determine: (1) the preferred (set of) urinary biomarker(s), (2) the preferred urinary collection period, and (3) a method to estimate the dietary exposure to these mycotoxins. Twenty adult volunteers were restricted in consuming cereals and cereal-based foods for 4 days. At day 3, a single dose of 1 µg/kg body weight of DON or DON3G was orally administered to 16 volunteers; 4 volunteers served as control. All individual urine discharges were collected during 24 h after administration. The metabolism and renal excretion could be described by a biokinetic model using three physiological compartments (gastrointestinal tract, liver, and kidneys). Kinetic analysis revealed a complete recovery of the renal excretion of total DON (mainly DON and its glucuronides) within 24 h after administration of DON or DON3G. The so-called ‘reverse dosimetry’ factor was used to determine the preferred (set of) biomarker(s) and to estimate the dietary intake of the parent compounds in the future. The fact that DON3G was absorbed and mainly excreted as DON and its glucuronides confirms that DON3G (as well as other modified forms) should be taken into account in the exposure and risk assessment of this group of mycotoxins. Full article

(This article belongs to the Special Issue Mycotoxin Biomarkers of Exposure)

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18 pages, 4543 KiB

Open AccessEditor’s ChoiceArticle

Investigation of Zearalenone Adsorption and Biotransformation by Microorganisms Cultured under Cellular Stress Conditions

by Agnieszka Rogowska, Paweł Pomastowski, Justyna Walczak, Viorica Railean-Plugaru, Joanna Rudnicka and Bogusław Buszewski

Toxins 2019, 11(8), 463; https://doi.org/10.3390/toxins11080463 - 7 Aug 2019

Cited by 25 | Viewed by 4349

Abstract

The zearalenone binding and metabolization ability of probiotic microorganisms, such as lactic acid bacteria, Lactobacillus paracasei, Lactococcus lactis, and yeast Saccharomyces cerevisiae, isolated from food products, were examined. Moreover, the influence of cellular stress (induced by silver nanoparticles) and lyophilization on the [...] Read more.

The zearalenone binding and metabolization ability of probiotic microorganisms, such as lactic acid bacteria, Lactobacillus paracasei, Lactococcus lactis, and yeast Saccharomyces cerevisiae, isolated from food products, were examined. Moreover, the influence of cellular stress (induced by silver nanoparticles) and lyophilization on the effectiveness of tested microorganisms was also investigated. The concentration of zearalenone after a certain time of incubation with microorganisms was determined using high-performance liquid chromatography. The maximum sorption effectiveness for L. paracasei, L. lactis, and S. cerevisiae cultured in non-stress conditions was 53.3, 41.0, and 36.5%, respectively. At the same time for the same microorganisms cultured at cellular stress conditions, the maximum sorption effectiveness was improved to 55.3, 47.4, and 57.0%, respectively. Also, the effect of culture conditions on the morphology of the cells and its metabolism was examined using microscopic technique and matrix-assisted laser desorption ionization-time of flight mass spectrometry, respectively. Full article

(This article belongs to the Collection Fusarium Toxins – Relevance for Human and Animal Health)

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18 pages, 1953 KiB

Open AccessEditor’s ChoiceArticle

Camelid VHHs Fused to Human Fc Fragments Provide Long Term Protection Against Botulinum Neurotoxin A in Mice

by Svetlana A. Godakova, Anatoly N. Noskov, Irina D. Vinogradova, Galina A. Ugriumova, Andrey I. Solovyev, Ilias B. Esmagambetov, Amir I. Tukhvatulin, Denis Y. Logunov, Boris S. Naroditsky, Dmitry V. Shcheblyakov and Aleksandr L. Gintsburg

Toxins 2019, 11(8), 464; https://doi.org/10.3390/toxins11080464 - 7 Aug 2019

Cited by 47 | Viewed by 5854

Abstract

The bacterium Clostridium botulinum is the causative agent of botulism—a severe intoxication caused by botulinum neurotoxin (BoNT) and characterized by damage to the nervous system. In an effort to develop novel C. botulinum immunotherapeutics, camelid single-domain antibodies (sdAbs, VHHs, or nanobodies) could be [...] Read more.

The bacterium Clostridium botulinum is the causative agent of botulism—a severe intoxication caused by botulinum neurotoxin (BoNT) and characterized by damage to the nervous system. In an effort to develop novel C. botulinum immunotherapeutics, camelid single-domain antibodies (sdAbs, VHHs, or nanobodies) could be used due to their unique structure and characteristics. In this study, VHHs were produced using phage display technology. A total of 15 different monoclonal VHHs were selected based on their comlementarity-determining region 3 (CDR3) sequences. Different toxin lethal dose (LD₅₀) challenges with each selected phage clone were conducted in vivo to check their neutralizing potency. We demonstrated that modification of neutralizing VHHs with a human immunoglobulin G (IgG)1 Fc (fragment crystallizable) fragment (fusionbody, VHH-Fc) significantly increased the circulation time in the blood (up to 14 days). At the same time, VHH-Fc showed the protective activity 1000 times higher than monomeric form when challenged with 5 LD₅₀. Moreover, VHH-Fcs remained protective even 14 days after antibody administration. These results indicate that this VHH-Fc could be used as an effective long term antitoxin protection against botulinum type A. Full article

(This article belongs to the Section Bacterial Toxins)

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9 pages, 732 KiB

Open AccessEditor’s ChoiceArticle

Evolution of Asian Corn Borer Resistance to Bt Toxins Used Singly or in Pairs

by Yueqin Wang, Yudong Quan, Jing Yang, Changlong Shu, Zhenying Wang, Jie Zhang, Angharad M. R. Gatehouse, Bruce E. Tabashnik and Kanglai He

Toxins 2019, 11(8), 461; https://doi.org/10.3390/toxins11080461 - 6 Aug 2019

Cited by 11 | Viewed by 4304

Abstract

Transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt) have revolutionized pest control, but the benefits of this approach have been reduced by the evolution of resistance in pests. The widely adopted ’pyramid strategy’ for delaying resistance entails transgenic crops producing two or [...] Read more.

Transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt) have revolutionized pest control, but the benefits of this approach have been reduced by the evolution of resistance in pests. The widely adopted ’pyramid strategy’ for delaying resistance entails transgenic crops producing two or more distinct toxins that kill the same pest. The limited experimental evidence supporting this strategy comes primarily from a model system under ideal conditions. Here we tested the pyramid strategy under nearly worst-case conditions, including some cross-resistance between the toxins in the pyramid. In a laboratory selection experiment with an artificial diet, we used Bt toxins Cry1Ab, Cry1F, and Cry1Ie singly or in pairs against Ostrinia furnacalis, one of the most destructive pests of corn in Asia. Under the conditions evaluated, pairs of toxins did not consistently delay the evolution of resistance relative to single toxins. Full article

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22 pages, 1648 KiB

Open AccessEditor’s ChoiceReview

Biological Control of Citrus Postharvest Phytopathogens

by Jaqueline Moraes Bazioli, João Raul Belinato, Jonas Henrique Costa, Daniel Yuri Akiyama, João Guilherme de Moraes Pontes, Katia Cristina Kupper, Fabio Augusto, João Ernesto de Carvalho and Taícia Pacheco Fill

Toxins 2019, 11(8), 460; https://doi.org/10.3390/toxins11080460 - 6 Aug 2019

Cited by 113 | Viewed by 11390

Abstract

Citrus are vulnerable to the postharvest decay caused by Penicillium digitatum, Penicillium italicum, and Geotrichum citri-aurantii, which are responsible for the green mold, blue mold, and sour rot post-harvest disease, respectively. The widespread economic losses in citriculture caused by these [...] Read more.

Citrus are vulnerable to the postharvest decay caused by Penicillium digitatum, Penicillium italicum, and Geotrichum citri-aurantii, which are responsible for the green mold, blue mold, and sour rot post-harvest disease, respectively. The widespread economic losses in citriculture caused by these phytopathogens are minimized with the use of synthetic fungicides such as imazalil, thiabendazole, pyrimethanil, and fludioxonil, which are mainly employed as control agents and may have harmful effects on human health and environment. To date, numerous non-chemical postharvest treatments have been investigated for the control of these pathogens. Several studies demonstrated that biological control using microbial antagonists and natural products can be effective in controlling postharvest diseases in citrus, as well as the most used commercial fungicides. Therefore, microbial agents represent a considerably safer and low toxicity alternative to synthetic fungicides. In the present review, these biological control strategies as alternative to the chemical fungicides are summarized here and new challenges regarding the development of shelf-stable formulated biocontrol products are also discussed. Full article

(This article belongs to the Special Issue Novel Approaches to Minimising Mycotoxin Contamination)

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24 pages, 1060 KiB

Open AccessEditor’s ChoiceReview

Mechanisms of Botulinum Toxin Type A Action on Pain

by Ivica Matak, Kata Bölcskei, Lidija Bach-Rojecky and Zsuzsanna Helyes

Toxins 2019, 11(8), 459; https://doi.org/10.3390/toxins11080459 - 5 Aug 2019

Cited by 149 | Viewed by 20550

Abstract

Already a well-established treatment for different autonomic and movement disorders, the use of botulinum toxin type A (BoNT/A) in pain conditions is now continuously expanding. Currently, the only approved use of BoNT/A in relation to pain is the treatment of chronic migraines. However, [...] Read more.

Already a well-established treatment for different autonomic and movement disorders, the use of botulinum toxin type A (BoNT/A) in pain conditions is now continuously expanding. Currently, the only approved use of BoNT/A in relation to pain is the treatment of chronic migraines. However, controlled clinical studies show promising results in neuropathic and other chronic pain disorders. In comparison with other conventional and non-conventional analgesic drugs, the greatest advantages of BoNT/A use are its sustained effect after a single application and its safety. Its efficacy in certain therapy-resistant pain conditions is of special importance. Novel results in recent years has led to a better understanding of its actions, although further experimental and clinical research is warranted. Here, we summarize the effects contributing to these advantageous properties of BoNT/A in pain therapy, specific actions along the nociceptive pathway, consequences of its central activities, the molecular mechanisms of actions in neurons, and general pharmacokinetic parameters. Full article

(This article belongs to the Special Issue Botulinum Toxin for Neuropathic Pain Treatment)

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19 pages, 3296 KiB

Open AccessEditor’s ChoiceArticle

Diagnosing Microcystin Intoxication of Canines: Clinicopathological Indications, Pathological Characteristics, and Analytical Detection in Postmortem and Antemortem Samples

by Amanda J. Foss, Mark T. Aubel, Brandi Gallagher, Nancy Mettee, Amanda Miller and Susan B. Fogelson

Toxins 2019, 11(8), 456; https://doi.org/10.3390/toxins11080456 - 3 Aug 2019

Cited by 25 | Viewed by 6285

Abstract

In the summer of 2018, six dogs exposed to a harmful algal bloom (HAB) of Microcystis in Martin County Florida (USA) developed clinicopathological signs of microcystin (MC) intoxication (i.e., acute vomiting, diarrhea, severe thrombocytopenia, elevated alanine aminotransferase, hemorrhage). Successful supportive veterinary care was [...] Read more.

In the summer of 2018, six dogs exposed to a harmful algal bloom (HAB) of Microcystis in Martin County Florida (USA) developed clinicopathological signs of microcystin (MC) intoxication (i.e., acute vomiting, diarrhea, severe thrombocytopenia, elevated alanine aminotransferase, hemorrhage). Successful supportive veterinary care was provided and led to survival of all but one patient. Confirmation of MC intoxication was made through interpretation of clinicopathological abnormalities, pathological examination of tissues, microscopy (vomitus), and analytical MC testing of antemortem/postmortem samples (vomitus, blood, urine, bile, liver, kidney, hair). Gross and microscopic examination of the deceased patient confirmed massive hepatic necrosis, mild multifocal renal tubular necrosis, and hemorrhage within multiple organ systems. Microscopy of a vomitus sample confirmed the presence of Microcystis. Three analytical MC testing approaches were used, including the MMPB (2-methyl-3-methoxy-4-phenylbutyric acid) technique, targeted congener analysis (e.g., liquid chromatography tandem-mass spectrometry of MC-LR), and enzyme-linked immunosorbent assay (ELISA). Total Adda MCs (as MMPB) were confirmed in the liver, bile, kidney, urine, and blood of the deceased dog. Urinalysis (MMPB) of one surviving dog showed a high level of MCs (32,000 ng mL⁻¹) 1-day post exposure, with MCs detectable >2 months post exposure. Furthermore, hair from a surviving dog was positive for MMPB, illustrating another testable route of MC elimination in canines. The described cases represent the first use of urine as an antemortem, non-invasive specimen to diagnose microcystin toxicosis. Antemortem diagnostic testing to confirm MC intoxication cases, whether acute or chronic, is crucial for providing optimal supportive care and mitigating MC exposure. Full article

(This article belongs to the Special Issue Freshwater Algal Toxins: Monitoring and Toxicity Profile)

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18 pages, 3609 KiB

Open AccessEditor’s ChoiceArticle

Indoxyl Sulfate Stimulates Angiogenesis by Regulating Reactive Oxygen Species Production via CYP1B1

by Jiayi Pei, Rio Juni, Magdalena Harakalova, Dirk J. Duncker, Folkert W. Asselbergs, Pieter Koolwijk, Victor van Hinsbergh, Marianne C. Verhaar, Michal Mokry and Caroline Cheng

Toxins 2019, 11(8), 454; https://doi.org/10.3390/toxins11080454 - 2 Aug 2019

Cited by 14 | Viewed by 4095

Abstract

Indoxyl sulfate (IS) is an accumulative protein-bound uremic toxin found in patients with kidney disease. It is reported that IS impairs the vascular endothelium, but a comprehensive overview of all mechanisms active in IS-injury currently remains lacking. Here we performed RNA sequencing in [...] Read more.

Indoxyl sulfate (IS) is an accumulative protein-bound uremic toxin found in patients with kidney disease. It is reported that IS impairs the vascular endothelium, but a comprehensive overview of all mechanisms active in IS-injury currently remains lacking. Here we performed RNA sequencing in human umbilical vein endothelial cells (HUVECs) after IS or control medium treatment and identified 1293 genes that were affected in a IS-induced response. Gene enrichment analysis highlighted pathways involved in altered vascular formation and cell metabolism. We confirmed these transcriptome profiles at the functional level by demonstrating decreased viability and increased cell senescence in response to IS treatment. In line with the additional pathways highlighted by the transcriptome analysis, we further could demonstrate that IS exposure of HUVECs promoted tubule formation as shown by the increase in total tubule length in a 3D HUVECs/pericytes co-culture assay. Notably, the pro-angiogenic response of IS and increased ROS production were abolished when CYP1B1, one of the main target genes that was highly upregulated by IS, was silenced. This observation indicates IS-induced ROS in endothelial cells is CYP1B1-dependent. Taken together, our findings demonstrate that IS promotes angiogenesis and CYP1B1 is an important factor in IS-activated angiogenic response. Full article

(This article belongs to the Special Issue The Endothelial Effects of Uremic Toxins)

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18 pages, 1880 KiB

Open AccessEditor’s ChoiceArticle

Lack of Toxic Interaction between Fusariotoxins in Broiler Chickens Fed throughout Their Life at the Highest Level Tolerated in the European Union

by Jean-Paul Metayer, Angelique Travel, Amandine Mika, Jean-Denis Bailly, Didier Cleva, Cyril Boissieu, Jean Le Guennec, Pascal Froment, Olivier Albaric, Sophie Labrut, Gurvan Lepivert, Eric Marengue, Didier Tardieu and Philippe Guerre

Toxins 2019, 11(8), 455; https://doi.org/10.3390/toxins11080455 - 2 Aug 2019

Cited by 24 | Viewed by 4035

Abstract

Fusarium mycotoxins (FUS) occur frequently in poultry diets, and regulatory limits are laid down in several countries. However, the limits were established for exposure to a single mycotoxin, whereas multiple contamination is more realistic, and different studies have demonstrated that it is not [...] Read more.

Fusarium mycotoxins (FUS) occur frequently in poultry diets, and regulatory limits are laid down in several countries. However, the limits were established for exposure to a single mycotoxin, whereas multiple contamination is more realistic, and different studies have demonstrated that it is not possible to predict interactions between mycotoxins. The purpose of this study was thus to compare the toxic effect of deoxynivalenol (DON), fumonisins (FB) and zearalenone (ZON), alone and in combination on broiler chickens, at the maximum tolerated level established by the EU for poultry feed. Experimental corn-soybean diets incorporated ground cultured toxigenic Fusarium strains. One feed was formulated for chickens 0 to 10 days old and another for chickens 11 to 35 days old. The control diets were mycotoxin free, the DON diets contained 5 mg DON/kg, the FB diet contained 20 mg FB1 + FB2/kg, and the ZON diet contained 0.5 mg ZON/kg. The DONFBZON diet contained 5, 20, and 0.5 mg/kg of DON, FB1 + FB2, and ZON, respectively. Diets were distributed ad libitum to 70 broilers (male Ross PM3) separated into five groups of 14 chickens each reared in individual cages from one to 35 days of age. On day 35, after a starvation period of 8 h, a blood sample was collected, and all the animals were killed and autopsied. No difference between groups that could be attributed to FUS was observed in performances, the relative weight of organs, biochemistry, histopathology, intestinal morphometry, variables of oxidative damage, and markers of testicle toxicity. A significant increase in sphinganine and in the sphinganine to sphingosine ratio was observed in broilers fed FB. Taken together, these results suggest that the regulatory guidelines established for single contamination of broiler chickens fed with DON, FB, and ZON can also be used in the case of multiple contamination with these toxins. Full article

(This article belongs to the Special Issue Dietary Mycotoxin Exposure to Livestock and Poultry)

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11 pages, 2360 KiB

Open AccessEditor’s ChoiceArticle

Zearalenone Contamination in Corn, Corn Products, and Swine Feed in China in 2016–2018 as Assessed by Magnetic Bead Immunoassay

by Ming Li, Chuqin Yang, Yuhao Mao, Xia Hong and Daolin Du

Toxins 2019, 11(8), 451; https://doi.org/10.3390/toxins11080451 - 1 Aug 2019

Cited by 25 | Viewed by 4285

Abstract

In total, 405 samples of corn, corn products, and swine feed from China in 2016–2018 were surveyed for zearalenone (ZEN) contamination using a magnetic bead immunoassay-coupled biotin–streptavidin system (BAS-MBI). The developed BAS-MBI had a limit of detection (LOD) of 0.098 ng mL⁻¹ [...] Read more.

In total, 405 samples of corn, corn products, and swine feed from China in 2016–2018 were surveyed for zearalenone (ZEN) contamination using a magnetic bead immunoassay-coupled biotin–streptavidin system (BAS-MBI). The developed BAS-MBI had a limit of detection (LOD) of 0.098 ng mL⁻¹, with half-maximal inhibition concentration (IC₅₀) of 0.71 ng mL⁻¹ in working buffer, and an LOD of 0.98 ng g⁻¹; the detection range was from 0.98 to 51.6 ng g⁻¹ in authentic agricultural samples. The BAS-MBI has been demonstrated to be a powerful method for the rapid, sensitive, specific, and accurate determination of ZEN. The ZEN positivity rate reached the highest level of 40.6% in 133 samples in 2016; ZEN levels ranged from 1.8 to 1100.0 ng g⁻¹, with an average level of 217.9 ng g⁻¹. In 2017, the ZEN positivity rate was the lowest at 24.5% in 143 samples; ZEN levels ranged from 1.1 to 722.6 ng g⁻¹, with an average of 166.7 ng g⁻¹. In 2018, the ZEN positivity rate was 31.8% in 129 samples; ZEN levels ranged from 1.3 to 947.8 ng g⁻¹, with an average of 157.0 ng g⁻¹. About 20% of ZEN-positive samples exceeded maximum limit levels. An alternative method of ZEN detection and a valuable reference for ZEN contamination in corn and its related products in China are provided. This survey suggests the need for prevention of serious ZEN contamination, along with management for food safety and human health. Full article

(This article belongs to the Special Issue Advanced Methods for Mycotoxins Detection)

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27 pages, 18163 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Bottom-Up Proteomic Analysis of Polypeptide Venom Components of the Giant Ant Dinoponera Quadriceps

by Douglas Oscar Ceolin Mariano, Úrsula Castro de Oliveira, André Junqueira Zaharenko, Daniel Carvalho Pimenta, Gandhi Rádis-Baptista and Álvaro Rossan de Brandão Prieto-da-Silva

Toxins 2019, 11(8), 448; https://doi.org/10.3390/toxins11080448 - 29 Jul 2019

Cited by 16 | Viewed by 5232

Abstract

Ant species have specialized venom systems developed to sting and inoculate a biological cocktail of organic compounds, including peptide and polypeptide toxins, for the purpose of predation and defense. The genus Dinoponera comprises predatory giant ants that inoculate venom capable of causing long-lasting [...] Read more.

Ant species have specialized venom systems developed to sting and inoculate a biological cocktail of organic compounds, including peptide and polypeptide toxins, for the purpose of predation and defense. The genus Dinoponera comprises predatory giant ants that inoculate venom capable of causing long-lasting local pain, involuntary shaking, lymphadenopathy, and cardiac arrhythmias, among other symptoms. To deepen our knowledge about venom composition with regard to protein toxins and their roles in the chemical–ecological relationship and human health, we performed a bottom-up proteomics analysis of the crude venom of the giant ant D. quadriceps, popularly known as the “false” tocandiras. For this purpose, we used two different analytical approaches: (i) gel-based proteomics approach, wherein the crude venom was resolved by denaturing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and all protein bands were excised for analysis; (ii) solution-based proteomics approach, wherein the crude venom protein components were directly fragmented into tryptic peptides in solution for analysis. The proteomic data that resulted from these two methodologies were compared against a previously annotated transcriptomic database of D. quadriceps, and subsequently, a homology search was performed for all identified transcript products. The gel-based proteomics approach unequivocally identified nine toxins of high molecular mass in the venom, as for example, enzymes [hyaluronidase, phospholipase A1, dipeptidyl peptidase and glucose dehydrogenase/flavin adenine dinucleotide (FAD) quinone] and diverse venom allergens (homologous of the red fire ant Selenopsis invicta) and venom-related proteins (major royal jelly-like). Moreover, the solution-based proteomics revealed and confirmed the presence of several hydrolases, oxidoreductases, proteases, Kunitz-like polypeptides, and the less abundant inhibitor cysteine knot (ICK)-like (knottin) neurotoxins and insect defensin. Our results showed that the major components of the D. quadriceps venom are toxins that are highly likely to damage cell membranes and tissue, to cause neurotoxicity, and to induce allergic reactions, thus, expanding the knowledge about D. quadriceps venom composition and its potential biological effects on prey and victims. Full article

(This article belongs to the Special Issue Arthropod Venom Components and Their Potential Usage)

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22 pages, 6852 KiB

Open AccessEditor’s ChoiceArticle

Ostreopsis cf. ovata Bloom in Currais, Brazil: Phylogeny, Toxin Profile and Contamination of Mussels and Marine Plastic Litter

by Carlos Eduardo J. A. Tibiriçá, Isabel P. Leite, Talita V. V. Batista, Luciano F. Fernandes, Nicolas Chomérat, Fabienne Herve, Philipp Hess and Luiz L. Mafra

Toxins 2019, 11(8), 446; https://doi.org/10.3390/toxins11080446 - 27 Jul 2019

Cited by 46 | Viewed by 7986

Abstract

Ostreopsis cf. ovata is a toxic marine benthic dinoflagellate responsible for harmful blooms affecting ecosystem and human health, mostly in the Mediterranean Sea. In this study we report the occurrence of a summer O. cf. ovata bloom in Currais, a coastal archipelago located [...] Read more.

Ostreopsis cf. ovata is a toxic marine benthic dinoflagellate responsible for harmful blooms affecting ecosystem and human health, mostly in the Mediterranean Sea. In this study we report the occurrence of a summer O. cf. ovata bloom in Currais, a coastal archipelago located on the subtropical Brazilian coast (~25° S). This bloom was very similar to Mediterranean episodes in many aspects: (a) field-sampled and cultivated O. cf. ovata cells aligned phylogenetically (ITS and LSU regions) along with Mediterranean strains; (b) the bloom occurred at increasing temperature and irradiance, and decreasing wind speed; (c) cell densities reached up to 8.0 × 10⁴ cell cm⁻² on fiberglass screen and 5.6 × 10⁵ cell g⁻¹ fresh weight on seaweeds; (d) and toxin profiles were composed mostly of ovatoxin-a (58%) and ovatoxin-b (32%), up to 35.5 pg PLTX-eq. cell⁻¹ in total. Mussels were contaminated during the bloom with unsafe toxin levels (up to 131 µg PLTX-eq. kg⁻¹). Ostreopsis cells attached to different plastic litter, indicating an alternate route for toxin transfer to marine fauna via ingestion of biofilm-coated plastic debris. Full article

(This article belongs to the Special Issue Potentially Toxic Benthic Microorganisms in Freshwater and Marine Ecosystems)

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11 pages, 1798 KiB

Open AccessEditor’s ChoiceArticle

Abnormal Development of Hyalomma Marginatum Ticks (Acari: Ixodidae) Induced by Plant Cytotoxic Substances

by Alicja Buczek, Katarzyna Bartosik, Alicja M. Buczek, Weronika Buczek and Dorota Kulina

Toxins 2019, 11(8), 445; https://doi.org/10.3390/toxins11080445 - 26 Jul 2019

Cited by 11 | Viewed by 3564

Abstract

The increasing application of toxic plant substances to deter and fight ticks proves the need for investigations focused on the elucidation of their impact on the developmental stages and populations of these arthropods. We examined the course of embryogenesis and egg hatch in [...] Read more.

The increasing application of toxic plant substances to deter and fight ticks proves the need for investigations focused on the elucidation of their impact on the developmental stages and populations of these arthropods. We examined the course of embryogenesis and egg hatch in Hyalomma marginatum ticks under the effect of cytotoxic plant substances. The investigations demonstrated that the length of embryonic development of egg batches treated with 20 μL of a 0.1875% colchicine solution did not differ significantly from that in the control group. Colchicine caused the high mortality of eggs (16.3%) and embryos (9.7%), disturbances in larval hatch (8.1%), and lower numbers of normal larval hatches (65.6%). In 0.2% of the larvae, colchicine induced anomalies in the idiosoma (67.6%) and gnathosoma (22.5%) as well as composite anomalies (8.5%). The study demonstrates that cytotoxic compounds with an effect similar to that of colchicine can reduce tick populations and cause teratological changes, which were observed in the specimens found during field studies. Since there are no data on the toxic effects of active plant substances on other organisms and the risk of development of tick resistance, a strategy for the use of such compounds in tick control and the management of plant products should be developed. Full article

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16 pages, 526 KiB

Open AccessEditor’s ChoiceArticle

Determination of Deoxynivalenol Biomarkers in Italian Urine Samples

by Barbara De Santis, Francesca Debegnach, Brunella Miano, Giorgio Moretti, Elisa Sonego, Antonio Chiaretti, Danilo Buonsenso and Carlo Brera

Toxins 2019, 11(8), 441; https://doi.org/10.3390/toxins11080441 - 25 Jul 2019

Cited by 24 | Viewed by 3379

Abstract

Deoxynivalenol (DON) is a mycotoxin mainly produced by Fusarium graminearum that can contaminate cereals and cereal-based foodstuff. Urinary DON levels can be used as biomarker for exposure assessment purposes. This study assessed urinary DON concentrations in Italian volunteers recruited by age group, namely [...] Read more.

Deoxynivalenol (DON) is a mycotoxin mainly produced by Fusarium graminearum that can contaminate cereals and cereal-based foodstuff. Urinary DON levels can be used as biomarker for exposure assessment purposes. This study assessed urinary DON concentrations in Italian volunteers recruited by age group, namely children, adolescents, adults, and the elderly. In addition, vulnerable groups, namely vegetarians and pregnant women, were included in the study. To determine the urinary DON, its glucuronide and de-epoxydated (DOM-1) forms, an indirect analytical approach was used, measuring free DON and total DON (as sum of free and glucuronides forms), before and after enzymatic treatment, respectively. Morning urine samples were collected on two consecutive days, from six different population groups, namely children, adolescent, adults, elderly, vegetarians and pregnant women. Total DON was measured in the 76% of the collected samples with the maximum incidences in children and adolescent age group. Urine samples from children and adolescent also showed the highest total DON levels, up to 17.0 ng/mg_creat. Pregnant women had the lowest positive samples per category (40% for day 1 and 43% for day 2, respectively), low mean levels of total DON (down to 2.84 ng/mg_creat) and median equal to 0 ng/mg_creat. Estimation of DON dietary intake reveals that 7.5% of the total population exceeds the TDI of 1 μg/kg bw/day set for DON, with children showing 40% of individuals surpassing this value (male, day 2). Full article

(This article belongs to the Special Issue Fate of Free, “Masked” and Conjugated/Modified forms of Mycotoxins)

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