Toxins

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Open AccessEditorial

Acknowledgement to Reviewers of Toxins in 2013

by Toxins Editorial Office

Toxins 2014, 6(2), 779-783; https://doi.org/10.3390/toxins6020779 - 24 Feb 2014

Viewed by 3380

The editors of Toxins would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2013. [...] Full article

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Open AccessArticle

Organ Damage and Hepatic Lipid Accumulation in Carp (Cyprinus carpio L.) after Feed-Borne Exposure to the Mycotoxin, Deoxynivalenol (DON)

by Constanze Pietsch, Carsten Schulz, Pere Rovira, Werner Kloas and Patricia Burkhardt-Holm

Toxins 2014, 6(2), 756-778; https://doi.org/10.3390/toxins6020756 - 21 Feb 2014

Cited by 51 | Viewed by 9066

Abstract

Deoxynivalenol (DON) frequently contaminates animal feed, including fish feed used in aquaculture. This study intends to further investigate the effects of DON on carp (Cyprinus carpio L.) at concentrations representative for commercial fish feeds. Experimental feeding with 352, 619 or 953 μg [...] Read more.

Deoxynivalenol (DON) frequently contaminates animal feed, including fish feed used in aquaculture. This study intends to further investigate the effects of DON on carp (Cyprinus carpio L.) at concentrations representative for commercial fish feeds. Experimental feeding with 352, 619 or 953 μg DON kg⁻¹ feed resulted in unaltered growth performance of fish during six weeks of experimentation, but increased lipid peroxidation was observed in liver, head kidney and spleen after feeding of fish with the highest DON concentration. These effects of DON were mostly reversible by two weeks of feeding the uncontaminated control diet. Histopathological scoring revealed increased liver damage in DON-treated fish, which persisted even after the recovery phase. At the highest DON concentration, significantly more fat, and consequently, increased energy content, was found in whole fish body homogenates. This suggests that DON affects nutrient metabolism in carp. Changes of lactate dehydrogenase (LDH) activity in kidneys and muscle and high lactate levels in serum indicate an effect of DON on anaerobic metabolism. Serum albumin was reduced by feeding the medium and a high dosage of DON, probably due to the ribotoxic action of DON. Thus, the present study provides evidence of the effects of DON on liver function and metabolism. Full article

(This article belongs to the Special Issue Recent Advances and Perspectives in Deoxynivalenol Research)

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Open AccessReview

Tetrodotoxin: Chemistry, Toxicity, Source, Distribution and Detection

by Vaishali Bane, Mary Lehane, Madhurima Dikshit, Alan O'Riordan and Ambrose Furey

Toxins 2014, 6(2), 693-755; https://doi.org/10.3390/toxins6020693 - 21 Feb 2014

Cited by 300 | Viewed by 33479

Abstract

Tetrodotoxin (TTX) is a naturally occurring toxin that has been responsible for human intoxications and fatalities. Its usual route of toxicity is via the ingestion of contaminated puffer fish which are a culinary delicacy, especially in Japan. TTX was believed to be confined [...] Read more.

Tetrodotoxin (TTX) is a naturally occurring toxin that has been responsible for human intoxications and fatalities. Its usual route of toxicity is via the ingestion of contaminated puffer fish which are a culinary delicacy, especially in Japan. TTX was believed to be confined to regions of South East Asia, but recent studies have demonstrated that the toxin has spread to regions in the Pacific and the Mediterranean. There is no known antidote to TTX which is a powerful sodium channel inhibitor. This review aims to collect pertinent information available to date on TTX and its analogues with a special emphasis on the structure, aetiology, distribution, effects and the analytical methods employed for its detection. Full article

(This article belongs to the Collection Marine and Freshwater Toxins)

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Open AccessArticle

Light Influences How the Fungal Toxin Deoxynivalenol Affects Plant Cell Death and Defense Responses

by Khairul I. Ansari, Siamsa M. Doyle, Joanna Kacprzyk, Mojibur R. Khan, Stephanie Walter, Josephine M. Brennan, Chanemouga Soundharam Arunachalam, Paul F. McCabe and Fiona M. Doohan

Toxins 2014, 6(2), 679-692; https://doi.org/10.3390/toxins6020679 - 20 Feb 2014

Cited by 12 | Viewed by 8096

Abstract

The Fusarium mycotoxin deoxynivalenol (DON) can cause cell death in wheat (Triticum aestivum), but can also reduce the level of cell death caused by heat shock in Arabidopsis (Arabidopsis thaliana) cell cultures. We show that 10 μg mL⁻¹ [...] Read more.

The Fusarium mycotoxin deoxynivalenol (DON) can cause cell death in wheat (Triticum aestivum), but can also reduce the level of cell death caused by heat shock in Arabidopsis (Arabidopsis thaliana) cell cultures. We show that 10 μg mL⁻¹ DON does not cause cell death in Arabidopsis cell cultures, and its ability to retard heat-induced cell death is light dependent. Under dark conditions, it actually promoted heat-induced cell death. Wheat cultivars differ in their ability to resist this toxin, and we investigated if the ability of wheat to mount defense responses was light dependent. We found no evidence that light affected the transcription of defense genes in DON-treated roots of seedlings of two wheat cultivars, namely cultivar CM82036 that is resistant to DON-induced bleaching of spikelet tissue and cultivar Remus that is not. However, DON treatment of roots led to genotype-dependent and light-enhanced defense transcript accumulation in coleoptiles. Wheat transcripts encoding a phenylalanine ammonia lyase (PAL) gene (previously associated with Fusarium resistance), non-expressor of pathogenesis-related genes-1 (NPR1) and a class III plant peroxidase (POX) were DON-upregulated in coleoptiles of wheat cultivar CM82036 but not of cultivar Remus, and DON-upregulation of these transcripts in cultivar CM82036 was light enhanced. Light and genotype-dependent differences in the DON/DON derivative content of coleoptiles were also observed. These results, coupled with previous findings regarding the effect of DON on plants, show that light either directly or indirectly influences the plant defense responses to DON. Full article

(This article belongs to the Special Issue Recent Advances and Perspectives in Deoxynivalenol Research)

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Open AccessReview

Protein-Bound Uremic Toxins: New Culprits of Cardiovascular Events in Chronic Kidney Disease Patients

by Shunsuke Ito and Masayuki Yoshida

Toxins 2014, 6(2), 665-678; https://doi.org/10.3390/toxins6020665 - 20 Feb 2014

Cited by 140 | Viewed by 12217

Abstract

Chronic kidney disease (CKD) has been considered a major risk factor for cardiovascular diseases. Although great advances have recently been made in the pathophysiology and treatment of cardiovascular diseases, CKD remains a major global health problem. Moreover, the occurrence rates of cardiovascular events [...] Read more.

Chronic kidney disease (CKD) has been considered a major risk factor for cardiovascular diseases. Although great advances have recently been made in the pathophysiology and treatment of cardiovascular diseases, CKD remains a major global health problem. Moreover, the occurrence rates of cardiovascular events among CKD patients increase even in cases in which patients undergo hemodialysis, and the mechanisms underlying the so-called “cardiorenal syndrome” are not clearly understood. Recently, small-molecule uremic toxins have been associated with cardiovascular mortality in CKD and/or dialysis patients. These toxins range from small uncharged solutes to large protein-bound structures. In this review, we focused on protein-bound uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, which are poorly removed by current dialysis techniques. Several studies have demonstrated that protein-bound uremic toxins, especially indoxyl sulfate, induce vascular inflammation, endothelial dysfunction, and vascular calcification, which may explain the relatively poor prognosis of CKD and dialysis patients. The aim of this review is to provide novel insights into the effects of indoxyl sulfate and p-cresyl sulfate on the pathogenesis of atherosclerosis. Full article

(This article belongs to the Special Issue Uremic Toxins)

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Open AccessArticle

Breakdown of Phosphatidylserine Asymmetry Following Treatment of Erythrocytes with Lumefantrine

by Kousi Alzoubi, Bassel Alktifan, Gergely Oswald, Myriam Fezai, Majed Abed and Florian Lang

Toxins 2014, 6(2), 650-664; https://doi.org/10.3390/toxins6020650 - 20 Feb 2014

Cited by 10 | Viewed by 6058

Abstract

Background: Lumefantrine, a commonly used antimalarial drug, inhibits hemozoin formation in parasites. Several other antimalarial substances counteract parasitemia by triggering suicidal death or eryptosis of infected erythrocytes. Eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine-exposure at the erythrocyte [...] Read more.

Background: Lumefantrine, a commonly used antimalarial drug, inhibits hemozoin formation in parasites. Several other antimalarial substances counteract parasitemia by triggering suicidal death or eryptosis of infected erythrocytes. Eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine-exposure at the erythrocyte surface. Signaling involved in eryptosis include increase of cytosolic Ca²⁺-activity ([Ca²⁺]_i), formation of ceramide, oxidative stress and/or activation of p38 kinase, protein kinase C (PKC), or caspases. The present study explored, whether lumefantrine stimulates eryptosis. Methods: Cell volume has been estimated from forward scatter, phosphatidylserine-exposure from annexin V binding, [Ca²⁺]_i from Fluo3-fluorescence, reactive oxygen species from 2',7'-dichlorodihydrofluorescein-diacetate fluorescence, content of reduced glutathione (GSH) from mercury orange fluorescence, and ceramide abundance from binding of fluorescent antibodies in flow cytometry. Results: A 48 h exposure to lumefantrine (3 µg/mL) was followed by a significant increase of annexin-V-binding without significantly altering forward scatter, [Ca²⁺]_i, ROS formation, reduced GSH, or ceramide abundance. The annexin-V-binding following lumefantrine treatment was not significantly modified by p38 kinase inhibitors SB203580 (2 μM) and p38 Inh III (1 μM), PKC inhibitor staurosporine (1 µM) or pancaspase inhibitor zVAD (1 or 10 µM). Conclusions: Lumefantrine triggers cell membrane scrambling, an effect independent from entry of extracellular Ca²⁺, ceramide formation, ROS formation, glutathione content, p38 kinase, PKC or caspases. Full article

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Open AccessArticle

Antitumor Cell-Complex Vaccines Employing Genetically Modified Tumor Cells and Fibroblasts

by Antonio Miguel, María José Herrero, Luis Sendra, Rafael Botella, Ana Diaz, Rosa Algás and Salvador F. Aliño

Toxins 2014, 6(2), 636-649; https://doi.org/10.3390/toxins6020636 - 19 Feb 2014

Cited by 2 | Viewed by 5893

Abstract

The present study evaluates the immune response mediated by vaccination with cell complexes composed of irradiated B16 tumor cells and mouse fibroblasts genetically modified to produce GM-CSF. The animals were vaccinated with free B16 cells or cell complexes. We employed two gene plasmid [...] Read more.

The present study evaluates the immune response mediated by vaccination with cell complexes composed of irradiated B16 tumor cells and mouse fibroblasts genetically modified to produce GM-CSF. The animals were vaccinated with free B16 cells or cell complexes. We employed two gene plasmid constructions: one high producer (pMok) and a low producer (p2F). Tumor transplant was performed by injection of B16 tumor cells. Plasma levels of total IgG and its subtypes were measured by ELISA. Tumor volumes were measured and survival curves were obtained. The study resulted in a cell complex vaccine able to stimulate the immune system to produce specific anti-tumor membrane proteins (TMP) IgG. In the groups vaccinated with cells transfected with the low producer plasmid, IgG production was higher when we used free B16 cell rather than cell complexes. Nonspecific autoimmune response caused by cell complex was not greater than that induced by the tumor cells alone. Groups vaccinated with B16 transfected with low producer plasmid reached a tumor growth delay of 92% (p ≤ 0.01). When vaccinated with cell complex, the best group was that transfected with high producer plasmid, reaching a tumor growth inhibition of 56% (p ≤ 0.05). Significant survival (40%) was only observed in the groups vaccinated with free transfected B16 cells. Full article

(This article belongs to the Collection Toxicity and Therapeutic Interventions in the Immune System)

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Open AccessArticle

Botulinum Neurotoxin A Complex Recognizes Host Carbohydrates through Its Hemagglutinin Component

by Guorui Yao, Kwangkook Lee, Shenyan Gu, Kwok-Ho Lam and Rongsheng Jin

Toxins 2014, 6(2), 624-635; https://doi.org/10.3390/toxins6020624 - 12 Feb 2014

Cited by 17 | Viewed by 7069

Abstract

Botulinum neurotoxins (BoNTs) are potent bacterial toxins. The high oral toxicity of BoNTs is largely attributed to the progenitor toxin complex (PTC), which is assembled from BoNT and nontoxic neurotoxin-associated proteins (NAPs) that are produced together with BoNT in bacteria. Here, we performed [...] Read more.

Botulinum neurotoxins (BoNTs) are potent bacterial toxins. The high oral toxicity of BoNTs is largely attributed to the progenitor toxin complex (PTC), which is assembled from BoNT and nontoxic neurotoxin-associated proteins (NAPs) that are produced together with BoNT in bacteria. Here, we performed ex vivo studies to examine binding of the highly homogeneous recombinant NAPs to mouse small intestine. We also carried out the first comprehensive glycan array screening with the hemagglutinin (HA) component of NAPs. Our data confirmed that intestinal binding of the PTC is partly mediated by the HA moiety through multivalent interactions between HA and host carbohydrates. The specific HA-carbohydrate recognition could be inhibited by receptor-mimicking saccharides. Full article

(This article belongs to the Special Issue Neurotoxins: Health Threats and Biological Tools)

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Open AccessReview

Deficient Glutathione in the Pathophysiology of Mycotoxin-Related Illness

by Frederick T. Guilford and Janette Hope

Toxins 2014, 6(2), 608-623; https://doi.org/10.3390/toxins6020608 - 10 Feb 2014

Cited by 42 | Viewed by 23580

Abstract

Evidence for the role of oxidative stress in the pathophysiology of mycotoxin-related illness is increasing. The glutathione antioxidant and detoxification systems play a major role in the antioxidant function of cells. Exposure to mycotoxins in humans requires the production of glutathione on an [...] Read more.

Evidence for the role of oxidative stress in the pathophysiology of mycotoxin-related illness is increasing. The glutathione antioxidant and detoxification systems play a major role in the antioxidant function of cells. Exposure to mycotoxins in humans requires the production of glutathione on an “as needed” basis. Research suggests that mycotoxins can decrease the formation of glutathione due to decreased gene expression of the enzymes needed to form glutathione. Mycotoxin-related compromise of glutathione production can result in an excess of oxidative stress that leads to tissue damage and systemic illness. The review discusses the mechanisms by which mycotoxin-related deficiency of glutathione may lead to both acute and chronic illnesses. Full article

(This article belongs to the Special Issue Mycotoxins and Human Diseases)

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Open AccessArticle

Time Course Analysis of the Effects of Botulinum Neurotoxin Type A on Pain and Vasomotor Responses Evoked by Glutamate Injection into Human Temporalis Muscles

by Larissa Bittencourt Da Silva, Dolarose Kulas, Ali Karshenas, Brian E. Cairns, Flemming W. Bach, Lars Arendt-Nielsen and Parisa Gazerani

Toxins 2014, 6(2), 592-607; https://doi.org/10.3390/toxins6020592 - 10 Feb 2014

Cited by 19 | Viewed by 6050

Abstract

The effect of botulinum neurotoxin type A (BoNTA) on glutamate-evoked temporalis muscle pain and vasomotor responses was investigated in healthy men and women over a 60 day time course. Subjects participated in a pre-BoNTA session where their responses to injection of glutamate [...] Read more.

The effect of botulinum neurotoxin type A (BoNTA) on glutamate-evoked temporalis muscle pain and vasomotor responses was investigated in healthy men and women over a 60 day time course. Subjects participated in a pre-BoNTA session where their responses to injection of glutamate (1 M, 0.2 mL) and saline (0.2 mL) into the temporalis muscles were assessed. On Day 1, BoNTA (5 U) was injected into one temporalis muscle and saline into the contralateral temporalis muscle, in a randomized order. Subjects then received intramuscular injections of glutamate (1 M, 0.2 mL) into the left and right temporalis muscles at 3 h and subsequently 7, 30 and 60 days post-injection of BoNTA. Pain intensity, pain area, and neurogenic inflammation (skin temperature and skin blood perfusion) were recorded. Prior to BoNTA treatment, glutamate evoked significantly greater pain and vasomotor reactions (P < 0.001) than saline. BoNTA significantly reduced glutamate-evoked pain intensity (P < 0.05), pain area (P < 0.01), skin blood perfusion (P < 0.05), and skin temperature (P < 0.001). The inhibitory effect of BoNTA was present at 3 h after injection, peaked after 7 days and returned to baseline by 60 days. Findings from the present study demonstrated a rapid action of BoNTA on glutamate-evoked pain and neurogenic inflammation, which is in line with animal studies. Full article

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Open AccessArticle

Deoxynivalenol and Oxidative Stress Indicators in Winter Wheat Inoculated with Fusarium graminearum

by Agnieszka Waśkiewicz, Iwona Morkunas, Waldemar Bednarski, Van Chung Mai, Magda Formela, Monika Beszterda, Halina Wiśniewska and Piotr Goliński

Toxins 2014, 6(2), 575-591; https://doi.org/10.3390/toxins6020575 - 7 Feb 2014

Cited by 22 | Viewed by 6735

Abstract

This study comprises analyses of contents of mycotoxins, such as deoxynivalenol and zearalenone, as well as the level of oxidative stress in ears of a susceptible wheat cultivar Hanseat and cv. Arina, resistant to a pathogenic fungus Fusarium graminearum. Starting from 48 [...] Read more.

This study comprises analyses of contents of mycotoxins, such as deoxynivalenol and zearalenone, as well as the level of oxidative stress in ears of a susceptible wheat cultivar Hanseat and cv. Arina, resistant to a pathogenic fungus Fusarium graminearum. Starting from 48 h after inoculation, a marked increase was observed in the contents of these mycotoxins in ears of wheat; however, the greatest accumulation was recorded in the late period after inoculation, i.e., during development of disease. Up to 120 h after inoculation, in ears of both wheat cultivars, the level of deoxynivalenol was higher than that of zearalenone. The susceptible cultivar was characterized by a much greater accumulation of deoxynivalenol than the resistant cultivar. At the same time, in this cultivar, in the time from 0 to 72 h after inoculation, a marked post-infection increase was observed in the generation of the superoxide radical (O₂^•−). Additionally, its level, at all the time points after inoculation, was higher than in the control. In wheat cv. Arina, a markedly higher level of O₂^•− generation in relation to the control was found up to two hours after inoculation and, next, at a later time after inoculation. In turn, the level of semiquinone radicals detected by electron paramagnetic resonance (EPR) increased at later culture times, both in cv. Hanseat and Arina; however, in infested ears of wheat, it was generally lower than in the control. Analysis of disease symptoms revealed the presence of more extensive lesions in ears of a susceptible wheat cv. Hanseat than resistant cv. Arina. Additionally, ergosterol level as a fungal growth indicator was higher in ears of susceptible wheat than in the resistant cultivar. Full article

(This article belongs to the Special Issue Recent Advances and Perspectives in Deoxynivalenol Research)

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Open AccessReview

Soluble T Cell Receptor Vβ Domains Engineered for High-Affinity Binding to Staphylococcal or Streptococcal Superantigens

by Preeti Sharma, Ningyan Wang and David M. Kranz

Toxins 2014, 6(2), 556-574; https://doi.org/10.3390/toxins6020556 - 28 Jan 2014

Cited by 10 | Viewed by 8727

Abstract

Staphylococcus aureus and group A Streptococcus secrete a collection of toxins called superantigens (SAgs), so-called because they stimulate a large fraction of an individual’s T cells. One consequence of this hyperactivity is massive cytokine release leading to severe tissue inflammation and, in some [...] Read more.

Staphylococcus aureus and group A Streptococcus secrete a collection of toxins called superantigens (SAgs), so-called because they stimulate a large fraction of an individual’s T cells. One consequence of this hyperactivity is massive cytokine release leading to severe tissue inflammation and, in some cases, systemic organ failure and death. The molecular basis of action involves the binding of the SAg to both a T cell receptor (TCR) on a T cell and a class II product of the major histocompatibility complex (MHC) on an antigen presenting cell. This cross-linking leads to aggregation of the TCR complex and signaling. A common feature of SAgs is that they bind with relatively low affinity to the variable region (V) of the beta chain of the TCR. Despite this low affinity binding, SAgs are very potent, as each T cell requires only a small fraction of their receptors to be bound in order to trigger cytokine release. To develop high-affinity agents that could neutralize the activity of SAgs, and facilitate the development of detection assays, soluble forms of the Vβ regions have been engineered to affinities that are up to 3 million-fold higher for the SAg. Over the past decade, six different Vβ regions against SAgs from S. aureus (SEA, SEB, SEC3, TSST-1) or S. pyogenes (SpeA and SpeC) have been engineered for high-affinity using yeast display and directed evolution. Here we review the engineering of these high-affinity Vβ proteins, structural features of the six different SAgs and the Vβ proteins, and the specific properties of the engineered Vβ regions that confer high-affinity and specificity for their SAg ligands. Full article

(This article belongs to the Special Issue Enterotoxins: Microbial Proteins and Host Cell Dysregulation)

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Open AccessReview

Food Poisonings by Ingestion of Cyprinid Fish

by Manabu Asakawa and Tamao Noguchi

Toxins 2014, 6(2), 539-555; https://doi.org/10.3390/toxins6020539 - 28 Jan 2014

Cited by 12 | Viewed by 8810

Abstract

Raw or dried gallbladders of cyprinid fish have long been ingested as a traditional medicine in the Asian countries, particularly in China, for ameliorating visual acuity, rheumatism, and general health; however, sporadic poisoning incidences have occurred after their ingestion. The poisoning causes complex [...] Read more.

Raw or dried gallbladders of cyprinid fish have long been ingested as a traditional medicine in the Asian countries, particularly in China, for ameliorating visual acuity, rheumatism, and general health; however, sporadic poisoning incidences have occurred after their ingestion. The poisoning causes complex symptoms in patients, including acute renal failure, liver dysfunction, paralysis, and convulsions of limbs. The causative substance for the poisoning was isolated, and its basic properties were examined. The purified toxin revealed a minimum lethal dose of 2.6 mg/20 g in mouse, when injected intraperitoneally. The main symptoms were paralysis and convulsions of the hind legs, along with other neurological signs. Liver biopsy of the euthanized mice clearly exhibited hepatocytes necrosis and infiltration of neutrophils and lymphocytes, suggesting the acute dysfunction of the liver. Blood tests disclosed the characteristics of acute renal failure and liver injury. Infrared (IR) spectrometry, fast atom bombardment (FAB) mass spectrometry, and ¹H- and ¹³C-nuclear magnetic resonance (NMR) analysis indicated, a molecular formula of C₂₇H₄₈O₈S, containing a sulfate ester group for the toxin. Thus, we concluded that the structure of carp toxin to be 5α-cyprinol sulfate (5α-cholestane-3α, 7α, 12α, 26, 27-pentol 26-sulfate). This indicated that carp toxin is a nephro- and hepato- toxin, which could be the responsible toxin for carp bile poisoning in humans. Full article

(This article belongs to the Collection Marine and Freshwater Toxins)

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Open AccessArticle

Assessment of Multi-Mycotoxin Exposure in Southern Italy by Urinary Multi-Biomarker Determination

by Michele Solfrizzo, Lucia Gambacorta and Angelo Visconti

Toxins 2014, 6(2), 523-538; https://doi.org/10.3390/toxins6020523 - 28 Jan 2014

Cited by 168 | Viewed by 9113

Abstract

Human exposure assessment to deoxynivalenol (DON), aflatoxin B1 (AFB1), fumonisin B1 (FB1), zearalenone (ZEA) and ochratoxin A (OTA) can be performed by measuring their urinary biomarkers. Suitable biomarkers of exposure for these mycotoxins are DON + de-epoxydeoxynivalenol (DOM-1), aflatoxin M1 (AFM1), FB₁ [...] Read more.

Human exposure assessment to deoxynivalenol (DON), aflatoxin B1 (AFB1), fumonisin B1 (FB1), zearalenone (ZEA) and ochratoxin A (OTA) can be performed by measuring their urinary biomarkers. Suitable biomarkers of exposure for these mycotoxins are DON + de-epoxydeoxynivalenol (DOM-1), aflatoxin M1 (AFM1), FB₁, ZEA + α-zearalenol (α-ZOL) + β-zearalenol (β-ZOL) and OTA, respectively. An UPLC-MS/MS multi-biomarker method was used to detect and measure incidence and levels of these biomarkers in urine samples of 52 volunteers resident in Apulia region in Southern Italy. The presence of ZEA + ZOLs, OTA, DON, FB1 and AFM1were detected in 100%, 100%, 96%, 56% and 6%, of samples, respectively. All samples contained biomarkers of two or more mycotoxins. The mean concentrations of biomarkers ranged from 0.055 ng/mL (FB1) to 11.89 ng/mL (DON). Urinary biomarker concentrations were used to estimate human exposure to multiple mycotoxin. For OTA and DON, 94% and 40% of volunteers, respectively exceeded the tolerable daily intake (TDI) for these mycotoxins. The estimated human exposure to FB1 and ZEA was largely below the TDI for these mycotoxins for all volunteers. Full article

(This article belongs to the Special Issue Recent Advances and Perspectives in Deoxynivalenol Research)

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Open AccessArticle

Geographical Patterns in Cyanobacteria Distribution: Climate Influence at Regional Scale

by Frédéric Pitois, Isabelle Thoraval, Estelle Baurès and Olivier Thomas

Toxins 2014, 6(2), 509-522; https://doi.org/10.3390/toxins6020509 - 28 Jan 2014

Cited by 17 | Viewed by 6017

Abstract

Cyanobacteria are a component of public health hazards in freshwater environments because of their potential as toxin producers. Eutrophication has long been considered the main cause of cyanobacteria outbreak and proliferation, whereas many studies emphasized the effect of abiotic parameters (mainly temperature and [...] Read more.

Cyanobacteria are a component of public health hazards in freshwater environments because of their potential as toxin producers. Eutrophication has long been considered the main cause of cyanobacteria outbreak and proliferation, whereas many studies emphasized the effect of abiotic parameters (mainly temperature and light) on cell growth rate or toxin production. In view of the growing concerns of global change consequences on public health parameters, this study attempts to enlighten climate influence on cyanobacteria at regional scale in Brittany (NW France). The results show that homogeneous cyanobacteria groups are associated with climatic domains related to temperature, global radiation and pluviometry, whereas microcystins (MCs) occurrences are only correlated to local cyanobacteria species composition. As the regional climatic gradient amplitude is similar to the projected climate evolution on a 30-year timespan, a comparison between the present NW and SE situations was used to extrapolate the evolution of geographical cyanobacteria distribution in Brittany. Cyanobacteria composition should shift toward species associated with more frequent Microcystins occurrences along a NW/SE axis whereas lakes situated along a SW/NE axis should transition to species (mainly Nostocales) associated with lower MCs detection frequencies. Full article

(This article belongs to the Collection Marine and Freshwater Toxins)

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Open AccessArticle

Co-occurrence of the Cyanotoxins BMAA, DABA and Anatoxin-a in Nebraska Reservoirs, Fish, and Aquatic Plants

by Maitham Ahmed Al-Sammak, Kyle D. Hoagland, David Cassada and Daniel D. Snow

Toxins 2014, 6(2), 488-508; https://doi.org/10.3390/toxins6020488 - 28 Jan 2014

Cited by 112 | Viewed by 10501

Abstract

Several groups of microorganisms are capable of producing toxins in aquatic environments. Cyanobacteria are prevalent blue green algae in freshwater systems, and many species produce cyanotoxins which include a variety of chemical irritants, hepatotoxins and neurotoxins. Production and occurrence of potent neurotoxic cyanotoxins [...] Read more.

Several groups of microorganisms are capable of producing toxins in aquatic environments. Cyanobacteria are prevalent blue green algae in freshwater systems, and many species produce cyanotoxins which include a variety of chemical irritants, hepatotoxins and neurotoxins. Production and occurrence of potent neurotoxic cyanotoxins β-N-methylamino-l-alanine (BMAA), 2,4-diaminobutyric acid dihydrochloride (DABA), and anatoxin-a are especially critical with environmental implications to public and animal health. Biomagnification, though not well understood in aquatic systems, is potentially relevant to both human and animal health effects. Because little is known regarding their presence in fresh water, we investigated the occurrence and potential for bioaccumulation of cyanotoxins in several Nebraska reservoirs. Collection and analysis of 387 environmental and biological samples (water, fish, and aquatic plant) provided a snapshot of their occurrence. A sensitive detection method was developed using solid phase extraction (SPE) in combination with high pressure liquid chromatography-fluorescence detection (HPLC/FD) with confirmation by liquid chromatography-tandem mass spectrometry (LC/MS/MS). HPLC/FD detection limits ranged from 5 to 7 µg/L and LC/MS/MS detection limits were <0.5 µg/L, while detection limits for biological samples were in the range of 0.8–3.2 ng/g depending on the matrix. Based on these methods, measurable levels of these neurotoxic compounds were detected in approximately 25% of the samples, with detections of BMAA in about 18.1%, DABA in 17.1%, and anatoxin-a in 11.9%. Full article

(This article belongs to the Collection Marine and Freshwater Toxins)

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Open AccessArticle

Aedes aegypti Mos20 Cells Internalizes Cry Toxins by Endocytosis, and Actin Has a Role in the Defense against Cry11Aa Toxin

by Adriana Vega-Cabrera, Angeles Cancino-Rodezno, Helena Porta and Liliana Pardo-Lopez

Toxins 2014, 6(2), 464-487; https://doi.org/10.3390/toxins6020464 - 28 Jan 2014

Cited by 12 | Viewed by 6612

Abstract

Bacillus thuringiensis (Bt) Cry toxins are used to control Aedes aegypti, an important vector of dengue fever and yellow fever. Bt Cry toxin forms pores in the gut cells, provoking larvae death by osmotic shock. Little is known, however, about the endocytic [...] Read more.

Bacillus thuringiensis (Bt) Cry toxins are used to control Aedes aegypti, an important vector of dengue fever and yellow fever. Bt Cry toxin forms pores in the gut cells, provoking larvae death by osmotic shock. Little is known, however, about the endocytic and/or degradative cell processes that may counteract the toxin action at low doses. The purpose of this work is to describe the mechanisms of internalization and detoxification of Cry toxins, at low doses, into Mos20 cells from A. aegypti, following endocytotic and cytoskeletal markers or specific chemical inhibitors. Here, we show that both clathrin-dependent and clathrin-independent endocytosis are involved in the internalization into Mos20 cells of Cry11Aa, a toxin specific for Dipteran, and Cry1Ab, a toxin specific for Lepidoptera. Cry11Aa and Cry1Ab are not directed to secretory lysosomes. Instead, Mos20 cells use the Rab5 and Rab11 pathways as a common mechanism, most probably for the expulsion of Cry11Aa and Cry1Ab toxins. In conclusion, we propose that endocytosis is a mechanism induced by Cry toxins independently of specificity, probably as part of a basal immune response. We found, however, that actin is necessary for defense-specific response to Cry11Aa, because actin-silenced Mos20 cells become more sensitive to the toxic action of Cry11A toxin. Cry toxin internalization analysis in insect cell lines may contribute to a better understanding to Cry resistance in mosquitoes. Full article

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Open AccessArticle

Phytotoxicity Evaluation of Type B Trichothecenes Using a Chlamydomonas reinhardtii Model System

by Tadahiro Suzuki and Yumiko Iwahashi

Toxins 2014, 6(2), 453-463; https://doi.org/10.3390/toxins6020453 - 28 Jan 2014

Cited by 15 | Viewed by 5108

Abstract

Type B trichothecenes, which consist of deoxynivalenol (DON) and nivalenol (NIV) as the major end products, are produced by phytotoxic fungi, such as the Fusarium species, and pollute arable fields across the world. The DON toxicity has been investigated using various types of [...] Read more.

Type B trichothecenes, which consist of deoxynivalenol (DON) and nivalenol (NIV) as the major end products, are produced by phytotoxic fungi, such as the Fusarium species, and pollute arable fields across the world. The DON toxicity has been investigated using various types of cell systems or animal bioassays. The evaluation of NIV toxicity, however, has been relatively restricted because of its lower level compared with DON. In this study, the Chlamydomonas reinhardtii testing system, which has been reported to have adequate NIV sensitivity, was reinvestigated under different mycotoxin concentrations and light conditions. The best concentration of DON and NIV, and their derivatives, for test conditions was found to be 25 ppm (2.5 × 10⁻² mg/mL). In all light test conditions, DON, NIV, and fusarenon-X (FusX) indicated significant growth inhibition regardless of whether a light source existed, or under differential wavelength conditions. FusX growth was also influenced by changes in photon flux density. These results suggest that C. reinhardtii is an appropriate evaluation system for type B trichothecenes. Full article

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The Impact of Fusarium Mycotoxins on Human and Animal Host Susceptibility to Infectious Diseases

by Gunther Antonissen, An Martel, Frank Pasmans, Richard Ducatelle, Elin Verbrugghe, Virginie Vandenbroucke, Shaoji Li, Freddy Haesebrouck, Filip Van Immerseel and Siska Croubels

Toxins 2014, 6(2), 430-452; https://doi.org/10.3390/toxins6020430 - 28 Jan 2014

Cited by 233 | Viewed by 22269

Abstract

Contamination of food and feed with mycotoxins is a worldwide problem. At present, acute mycotoxicosis caused by high doses is rare in humans and animals. Ingestion of low to moderate amounts of Fusarium mycotoxins is common and generally does not result in obvious [...] Read more.

Contamination of food and feed with mycotoxins is a worldwide problem. At present, acute mycotoxicosis caused by high doses is rare in humans and animals. Ingestion of low to moderate amounts of Fusarium mycotoxins is common and generally does not result in obvious intoxication. However, these low amounts may impair intestinal health, immune function and/or pathogen fitness, resulting in altered host pathogen interactions and thus a different outcome of infection. This review summarizes the current state of knowledge about the impact of Fusarium mycotoxin exposure on human and animal host susceptibility to infectious diseases. On the one hand, exposure to deoxynivalenol and other Fusarium mycotoxins generally exacerbates infections with parasites, bacteria and viruses across a wide range of animal host species. Well-known examples include coccidiosis in poultry, salmonellosis in pigs and mice, colibacillosis in pigs, necrotic enteritis in poultry, enteric septicemia of catfish, swine respiratory disease, aspergillosis in poultry and rabbits, reovirus infection in mice and Porcine Reproductive and Respiratory Syndrome Virus infection in pigs. However, on the other hand, T-2 toxin has been shown to markedly decrease the colonization capacity of Salmonella in the pig intestine. Although the impact of the exposure of humans to Fusarium toxins on infectious diseases is less well known, extrapolation from animal models suggests possible exacerbation of, for instance, colibacillosis and salmonellosis in humans, as well. Full article

(This article belongs to the Special Issue Recent Advances and Perspectives in Deoxynivalenol Research)

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Open AccessArticle

Binding Affinity and Capacity for the Uremic Toxin Indoxyl Sulfate

by Eric Devine, Detlef H. Krieter, Marieke Rüth, Joachim Jankovski and Horst-Dieter Lemke

Toxins 2014, 6(2), 416-429; https://doi.org/10.3390/toxins6020416 - 24 Jan 2014

Cited by 45 | Viewed by 8809

Abstract

Protein binding prevents uremic toxins from removal by conventional extracorporeal therapies leading to accumulation in maintenance dialysis patients. Weakening of the protein binding may enhance the dialytic elimination of these toxins. In ultrafiltration and equilibrium dialysis experiments, different measures to modify the plasma [...] Read more.

Protein binding prevents uremic toxins from removal by conventional extracorporeal therapies leading to accumulation in maintenance dialysis patients. Weakening of the protein binding may enhance the dialytic elimination of these toxins. In ultrafiltration and equilibrium dialysis experiments, different measures to modify the plasma binding affinity and capacity were tested: (i), increasing the sodium chloride (NaCl) concentration to achieve a higher ionic strength; (ii), increasing the temperature; and (iii), dilution. The effects on the dissociation constant K_D and the protein bound fraction of the prototypical uremic toxin indoxyl sulfate (IS) in plasma of healthy and uremic individuals were studied. Binding of IS corresponded to one site binding in normal plasma. K_D increased linearly with the NaCl concentration between 0.15 (K_D = 13.2 ± 3.7 µM) and 0.75 M (K_D = 56.2 ± 2.0 µM). Plasma dilution further reduced the protein bound toxin fraction by lowering the protein binding capacity of the plasma. Higher temperatures also decreased the protein bound fraction of IS in human plasma. Increasing the NaCl concentration was effective to weaken the binding of IS also in uremic plasma: the protein bound fraction decreased from 89% ± 3% to 81% ± 3% at 0.15 and 0.75 M NaCl, respectively. Dilution and increasing the ionic strength and temperature enhance the free fraction of IS allowing better removal of the substance during dialysis. Applied during clinical dialysis, this may have beneficial effects on the long-term outcome of maintenance dialysis patients. Full article

(This article belongs to the Special Issue Uremic Toxins)

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Open AccessArticle

Detection of Anatoxin-a and Three Analogs in Anabaena spp. Cultures: New Fluorescence Polarization Assay and Toxin Profile by LC-MS/MS

by Jon A. Sanchez, Paz Otero, Amparo Alfonso, Vitor Ramos, Vitor Vasconcelos, Romulo Aráoz, Jordi Molgó, Mercedes R. Vieytes and Luis M. Botana

Toxins 2014, 6(2), 402-415; https://doi.org/10.3390/toxins6020402 - 24 Jan 2014

Cited by 27 | Viewed by 10115

Abstract

Anatoxin-a (ATX) is a potent neurotoxin produced by several species of Anabaena spp. Cyanobacteria blooms around the world have been increasing in recent years; therefore, it is urgent to develop sensitive techniques that unequivocally confirm the presence of these toxins in fresh [...] Read more.

Anatoxin-a (ATX) is a potent neurotoxin produced by several species of Anabaena spp. Cyanobacteria blooms around the world have been increasing in recent years; therefore, it is urgent to develop sensitive techniques that unequivocally confirm the presence of these toxins in fresh water and cyanobacterial samples. In addition, the identification of different ATX analogues is essential to later determine its toxicity. In this paper we designed a fluorescent polarization (FP) method to detect ATXs in water samples. A nicotinic acetylcholine receptor (nAChR) labeled with a fluorescein derivative was used to develop this assay. Data showed a direct relationship between the amount of toxin in a sample and the changes in the polarization degree of the emitted light by the labeled nAChR, indicating an interaction between the two molecules. This method was used to measure the amount of ATX in three Anabaena spp. cultures. Results indicate that it is a good method to show ATXs presence in algal samples. In order to check the toxin profile of Anabaena cultures a LC-MS/MS method was also developed. Within this new method, ATX-a, retention time (RT) 5 min, and three other molecules with a mass m/z 180.1 eluting at 4.14 min, 5.90 min and 7.14 min with MS/MS spectra characteristic of ATX toxin group not previously identified were detected in the Anabaena spp. cultures. These ATX analogues may have an important role in the toxicity of the sample. Full article

(This article belongs to the Collection Marine and Freshwater Toxins)

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Toxins, Volume 6, Issue 2 (February 2014) – 21 articles , Pages 402-783

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