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Toxins, Volume 5, Issue 11 (November 2013), Pages 1932-2292

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Research

Jump to: Review, Other

Open AccessArticle Effects of Vitamin D3, Calcipotriol and FTY720 on the Expression of Surface Molecules and Cytolytic Activities of Human Natural Killer Cells and Dendritic Cells
Toxins 2013, 5(11), 1932-1947; doi:10.3390/toxins5111932
Received: 22 September 2013 / Revised: 18 October 2013 / Accepted: 22 October 2013 / Published: 28 October 2013
Cited by 11 | PDF Full-text (2250 KB) | HTML Full-text | XML Full-text
Abstract
We describe here the effects of three drugs that are either approved or have the potential for treating multiple sclerosis (MS) patients through the in vitro activities of human natural killer (NK) cells and dendritic cells (DCs). Our results indicate that 1,25(OH)2
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We describe here the effects of three drugs that are either approved or have the potential for treating multiple sclerosis (MS) patients through the in vitro activities of human natural killer (NK) cells and dendritic cells (DCs). Our results indicate that 1,25(OH)2D3, the biologically active metabolite of vitamin D3, calcipotriol and FTY720 augment IL-2-activated NK cell lysis of K562 and RAJI tumor cell lines as well as immature (i) and mature (m) DCs, with variable efficacies. These results are corroborated with the ability of the drugs to up-regulate the expression of NK cytotoxicity receptors NKp30 and NKp44, as well as NKG2D on the surfaces of NK cells. Also, they down-regulate the expression of the killer inhibitory receptor CD158. The three drugs down-regulate the expression of CCR6 on the surface of iDCs, whereas vitamin D3 and calcipotriol tend to up-regulate the expression of CCR7 on mDCs, suggesting that they may influence the migration of DCs into the lymph nodes. Finally, vitamin D3, calcipotriol and FTY720 enhance NK17/NK1 cell lysis of K562 cells, suggesting that a possible mechanism of action for these drugs is via activating these newly described cells. In conclusion, our results show novel mechanisms of action for vitamin D3, calcipotriol and FTY720 on cells of the innate immune system. Full article
(This article belongs to the collection Toxicity and Therapeutic Interventions in the Immune System)
Open AccessArticle Atractaspis aterrima Toxins: The First Insight into the Molecular Evolution of Venom in Side-Stabbers
Toxins 2013, 5(11), 1948-1964; doi:10.3390/toxins5111948
Received: 17 September 2013 / Revised: 19 October 2013 / Accepted: 22 October 2013 / Published: 28 October 2013
Cited by 7 | PDF Full-text (2602 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Although snake venoms have been the subject of intense research, primarily because of their tremendous potential as a bioresource for design and development of therapeutic compounds, some specific groups of snakes, such as the genus Atractaspis, have been completely neglected. To date
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Although snake venoms have been the subject of intense research, primarily because of their tremendous potential as a bioresource for design and development of therapeutic compounds, some specific groups of snakes, such as the genus Atractaspis, have been completely neglected. To date only limited number of toxins, such as sarafotoxins have been well characterized from this lineage. In order to investigate the molecular diversity of venom from Atractaspis aterrima—the slender burrowing asp, we utilized a high-throughput transcriptomic approach completed with an original bioinformatics analysis pipeline. Surprisingly, we found that Sarafotoxins do not constitute the major ingredient of the transcriptomic cocktail; rather a large number of previously well-characterized snake venom-components were identified. Notably, we recovered a large diversity of three-finger toxins (3FTxs), which were found to have evolved under the significant influence of positive selection. From the normalized and non-normalized transcriptome libraries, we were able to evaluate the relative abundance of the different toxin groups, uncover rare transcripts, and gain new insight into the transcriptomic machinery. In addition to previously characterized toxin families, we were able to detect numerous highly-transcribed compounds that possess all the key features of venom-components and may constitute new classes of toxins. Full article
(This article belongs to the collection Evolution of Venom Systems)
Open AccessArticle Association between Free Light Chain Levels, and Disease Progression and Mortality in Chronic Kidney Disease
Toxins 2013, 5(11), 2058-2073; doi:10.3390/toxins5112058
Received: 24 September 2013 / Revised: 28 October 2013 / Accepted: 29 October 2013 / Published: 8 November 2013
Cited by 5 | PDF Full-text (326 KB) | HTML Full-text | XML Full-text
Abstract
Immunoglobulin free light chains (FLCs) form part of the middle molecule group of uremic toxins. Accumulation of FLCs has been observed in patients with chronic kidney disease (CKD). The aim of the present study was to measure FLC levels in patients at different
[...] Read more.
Immunoglobulin free light chains (FLCs) form part of the middle molecule group of uremic toxins. Accumulation of FLCs has been observed in patients with chronic kidney disease (CKD). The aim of the present study was to measure FLC levels in patients at different CKD stages and to assess putative associations between FLC levels on one hand and biochemical/clinical parameters and mortality on the other. One hundred and forty patients at CKD stages 2-5D were included in the present study. Routine clinical biochemistry assays and assays for FLC kappa (κ) and lambda (λ) and other uremic toxins were performed. Vascular calcification was evaluated using radiological techniques. The enrolled patients were prospectively monitored for mortality. Free light chain κ and λ levels were found to be elevated in CKD patients (especially in those on hemodialysis). Furthermore, FLC κ and λ levels were positively correlated with inflammation, aortic calcification and the levels of various uremic toxins levels. A multivariate linear regression analysis indicated that FLC κ and λ levels were independently associated with CKD stages and β2 microglobulin levels. Elevated FLC κ and λ levels appeared to be associated with mortality. However, this association disappeared after adjustment for a propensity score including age, CKD stage and aortic calcification. In conclusion, our results indicate that FLC κ and λ levels are elevated in CKD patients and are associated with inflammation, vascular calcification and levels of other uremic toxins. The observed link between elevated FLC levels and mortality appears to depend on other well-known factors. Full article
(This article belongs to the Special Issue Uremic Toxins)
Open AccessArticle Shiga Toxin Type 2dact Displays Increased Binding to Globotriaosylceramide in vitro and Increased Lethality in Mice after Activation by Elastase
Toxins 2013, 5(11), 2074-2092; doi:10.3390/toxins5112074
Received: 29 August 2013 / Revised: 31 October 2013 / Accepted: 4 November 2013 / Published: 8 November 2013
Cited by 5 | PDF Full-text (2220 KB) | HTML Full-text | XML Full-text
Abstract
Shiga toxin type 2dact (Stx2dact), an Stx2 variant originally identified from Escherichia coli O91:H21 strain B2F1, displays increased cytotoxicity after activation by elastase present in intestinal mucus. Activation is a result of cleavage of two amino acids from the C-terminal tail of the
[...] Read more.
Shiga toxin type 2dact (Stx2dact), an Stx2 variant originally identified from Escherichia coli O91:H21 strain B2F1, displays increased cytotoxicity after activation by elastase present in intestinal mucus. Activation is a result of cleavage of two amino acids from the C-terminal tail of the A2 subunit. In this study, we hypothesized that activation leads to increased binding of toxin to its receptor on host cells both in vitro and in vivo. To test this theory, Stx2dact was treated with elastase or buffer alone and then each toxin was assessed for binding to purified globotriaosylceramide (Gb3) in an enzyme-linked immunosorbent assay, or cells in culture by immunofluorescence, or flow cytometry. Elastase- and buffer-treated Stx2dact were also evaluated for binding to mouse kidney tissue and for relative lethality in mice. We found that activated Stx2dact had a greater capacity to bind purified Gb3, cells in culture, and mouse kidney tissue and was more toxic for mice than was non-activated Stx2dact. Thus, one possible mechanism for the augmented cytotoxicity of Stx2dact after activation is its increased capacity to bind target cells, which, in turn, may cause greater lethality of elastase-treated toxin for mice and enhanced virulence for humans of E. coli strains that express Stx2dact. Full article
(This article belongs to the Special Issue Novel Properties of Well-Characterized Toxins)
Open AccessArticle Oral Toxicity of Okadaic Acid in Mice: Study of Lethality, Organ Damage, Distribution and Effects on Detoxifying Gene Expression
Toxins 2013, 5(11), 2093-2108; doi:10.3390/toxins5112093
Received: 10 September 2013 / Revised: 15 October 2013 / Accepted: 5 November 2013 / Published: 8 November 2013
Cited by 3 | PDF Full-text (1864 KB) | HTML Full-text | XML Full-text
Abstract
In vivo, after administration by gavage to mice and rats, okadaic acid has been reported to produce lesions in liver, small intestine and forestomach. Because several reports differ in the damage detected in different organs, and on okadaic acid distribution after consumption,
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In vivo, after administration by gavage to mice and rats, okadaic acid has been reported to produce lesions in liver, small intestine and forestomach. Because several reports differ in the damage detected in different organs, and on okadaic acid distribution after consumption, we determined the toxicity of this compound after oral administration to mice. After 24 hours, histopathological examination showed necrotic foci and lipid vacuoles in the livers of intoxicated animals. By immunohistochemical analysis, we detected this toxin in the liver and kidneys of intoxicated animals. Okadaic acid induces oxidative stress and can be activated in vitro into reactive compounds by the post-mitochondrial S9 fraction, so we studied the okadaic effect on the gene expression of antioxidant and phase II detoxifying enzymes in liver. We observed a downregulation in the expression of these enzymes and a reduction of protein expression of catalase and superoxide dismutase 1 in intoxicated animals. Full article
(This article belongs to the collection Marine and Freshwater Toxins)
Open AccessArticle Potential Degradation of Swainsonine by Intracellular Enzymes of Arthrobacter sp. HW08
Toxins 2013, 5(11), 2161-2171; doi:10.3390/toxins5112161
Received: 4 September 2013 / Revised: 31 October 2013 / Accepted: 4 November 2013 / Published: 14 November 2013
Cited by 2 | PDF Full-text (3689 KB) | HTML Full-text | XML Full-text
Abstract
Swainsonine (SW) is a toxin produced by locoweeds and harmful to the livestock industry. Degrading SW by Arthrobacter sp. HW08 was demonstrated as a promising way to deal with SW poisoning. However, it is unknown which part of the subcellular enzymes in Arthrobacter
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Swainsonine (SW) is a toxin produced by locoweeds and harmful to the livestock industry. Degrading SW by Arthrobacter sp. HW08 was demonstrated as a promising way to deal with SW poisoning. However, it is unknown which part of the subcellular enzymes in Arthrobacter sp. HW08 is responsible for biodegrading SW and whether the metabolites are atoxic. In this study, intracellular and extracellular enzymes of Arthrobacter sp. HW08 were isolated and their enzyme activity was evaluated. The metabolites were fed to mice, and physiological and histological properties of the treated mice were investigated. The results showed that only intracellular enzyme of Arthrobacter sp. HW08 (IEHW08) could degrade SW efficiently. Compared with mice in SW treatment group, mice in SW + IEHW08 treatment group (1) increased their body weights; (2) showed higher number of platelets and lower number of white blood cells; (3) decreased the levels of creatinine, urea nitrogen, alanine transaminase and aspartate aminotransferase in serum; (4) reduced the number of vacuolated cells in cerebellum, liver and kidney. All these data demonstrate that IEHW08 was potentially safe for mice, while keeping the capacity of degrading SW. This study indicates a possible application of IEHW08 as an additive in the livestock industry to protect animals from SW poisoning. Full article
Open AccessArticle Three-Fingered RAVERs: Rapid Accumulation of Variations in Exposed Residues of Snake Venom Toxins
Toxins 2013, 5(11), 2172-2208; doi:10.3390/toxins5112172
Received: 2 October 2013 / Revised: 8 November 2013 / Accepted: 11 November 2013 / Published: 18 November 2013
Cited by 25 | PDF Full-text (1117 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Three-finger toxins (3FTx) represent one of the most abundantly secreted and potently toxic components of colubrid (Colubridae), elapid (Elapidae) and psammophid (Psammophiinae subfamily of the Lamprophidae) snake venom arsenal. Despite their conserved structural similarity, they perform a diversity of biological functions. Although they
[...] Read more.
Three-finger toxins (3FTx) represent one of the most abundantly secreted and potently toxic components of colubrid (Colubridae), elapid (Elapidae) and psammophid (Psammophiinae subfamily of the Lamprophidae) snake venom arsenal. Despite their conserved structural similarity, they perform a diversity of biological functions. Although they are theorised to undergo adaptive evolution, the underlying diversification mechanisms remain elusive. Here, we report the molecular evolution of different 3FTx functional forms and show that positively selected point mutations have driven the rapid evolution and diversification of 3FTx. These diversification events not only correlate with the evolution of advanced venom delivery systems (VDS) in Caenophidia, but in particular the explosive diversification of the clade subsequent to the evolution of a high pressure, hollow-fanged VDS in elapids, highlighting the significant role of these toxins in the evolution of advanced snakes. We show that Type I, II and III α-neurotoxins have evolved with extreme rapidity under the influence of positive selection. We also show that novel Oxyuranus/Pseudonaja Type II forms lacking the apotypic loop-2 stabilising cysteine doublet characteristic of Type II forms are not phylogenetically basal in relation to other Type IIs as previously thought, but are the result of secondary loss of these apotypic cysteines on at least three separate occasions. Not all 3FTxs have evolved rapidly: κ-neurotoxins, which form non-covalently associated heterodimers, have experienced a relatively weaker influence of diversifying selection; while cytotoxic 3FTx, with their functional sites, dispersed over 40% of the molecular surface, have been extremely constrained by negative selection. We show that the a previous theory of 3FTx molecular evolution (termed ASSET) is evolutionarily implausible and cannot account for the considerable variation observed in very short segments of 3FTx. Instead, we propose a theory of Rapid Accumulation of Variations in Exposed Residues (RAVER) to illustrate the significance of point mutations, guided by focal mutagenesis and positive selection in the evolution and diversification of 3FTx. Full article
(This article belongs to the collection Evolution of Venom Systems)
Open AccessArticle A Monoclonal Antibody Based Capture ELISA for Botulinum Neurotoxin Serotype B: Toxin Detection in Food
Toxins 2013, 5(11), 2212-2226; doi:10.3390/toxins5112212
Received: 6 September 2013 / Revised: 30 October 2013 / Accepted: 7 November 2013 / Published: 18 November 2013
Cited by 8 | PDF Full-text (496 KB) | HTML Full-text | XML Full-text
Abstract
Botulism is a serious foodborne neuroparalytic disease, caused by botulinum neurotoxin (BoNT), produced by the anaerobic bacterium Clostridium botulinum. Seven toxin serotypes (A–H) have been described. The majority of human cases of botulism are caused by serotypes A and B followed by
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Botulism is a serious foodborne neuroparalytic disease, caused by botulinum neurotoxin (BoNT), produced by the anaerobic bacterium Clostridium botulinum. Seven toxin serotypes (A–H) have been described. The majority of human cases of botulism are caused by serotypes A and B followed by E and F. We report here a group of serotype B specific monoclonal antibodies (mAbs) capable of binding toxin under physiological conditions. Thus, they serve as capture antibodies for a sandwich (capture) ELISA. The antibodies were generated using recombinant peptide fragments corresponding to the receptor-binding domain of the toxin heavy chain as immunogen. Their binding properties suggest that they bind a complex epitope with dissociation constants (KD’s) for individual antibodies ranging from 10 to 48 × 10−11 M. Assay performance for all possible combinations of capture-detector antibody pairs was evaluated and the antibody pair resulting in the lowest level of detection (L.O.D.), ~20 pg/mL was determined. Toxin was detected in spiked dairy samples with good recoveries at concentrations as low as 0.5 pg/mL and in ground beef samples at levels as low as 2 ng/g. Thus, the sandwich ELISA described here uses mAb for both the capture and detector antibodies (binding different epitopes on the toxin molecule) and readily detects toxin in those food samples tested. Full article
(This article belongs to the Special Issue Advances in Toxin Detection)
Open AccessArticle Impact of Antidepressants on Cytokine Production of Depressed Patients in Vitro
Toxins 2013, 5(11), 2227-2240; doi:10.3390/toxins5112227
Received: 5 September 2013 / Revised: 8 November 2013 / Accepted: 12 November 2013 / Published: 19 November 2013
Cited by 28 | PDF Full-text (279 KB) | HTML Full-text | XML Full-text
Abstract
The interplay between immune and nervous systems plays a pivotal role in the pathophysiology of depression. In depressive episodes, patients show increased production of pro-inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α. There is limited information on the effect of
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The interplay between immune and nervous systems plays a pivotal role in the pathophysiology of depression. In depressive episodes, patients show increased production of pro-inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α. There is limited information on the effect of antidepressant drugs on cytokines, most studies report on a limited sample of cytokines and none have reported effects on IL-22. We systematically investigated the effect of three antidepressant drugs, citalopram, escitalopram and mirtazapine, on secretion of cytokines IL-1β, IL-2, IL-4, IL-6, IL-17, IL-22 and TNF-α in a whole blood assay in vitro, using murine anti-human CD3 monoclonal antibody OKT3, and 5C3 monoclonal antibody against CD40, to stimulate T and B cells respectively. Citalopram increased production of IL-1β, IL-6, TNF-α and IL-22. Mirtazapine increased IL-1β, TNF-α and IL-22. Escitalopram decreased IL-17 levels. The influence of antidepressants on IL-2 and IL-4 levels was not significant for all three drugs. Compared to escitalopram, citalopram led to higher levels of IL-1β, IL-6, IL-17 and IL-22; and mirtazapine to higher levels of IL-1β, IL-17, IL-22 and TNF-α. Mirtazapine and citalopram increased IL-22 production. The differing profile of cytokine production may relate to differences in therapeutic effects, risk of relapse and side effects. Full article
(This article belongs to the collection Toxicity and Therapeutic Interventions in the Immune System)
Figures

Open AccessArticle Activation of RhoA,B,C by Yersinia Cytotoxic Necrotizing Factor (CNFy) Induces Apoptosis in LNCaP Prostate Cancer Cells
Toxins 2013, 5(11), 2241-2257; doi:10.3390/toxins5112241
Received: 4 September 2013 / Revised: 1 November 2013 / Accepted: 5 November 2013 / Published: 21 November 2013
Cited by 6 | PDF Full-text (1447 KB) | HTML Full-text | XML Full-text
Abstract
Prostate cancer is the most common malignancy, accounting for about 25% of all incident cases among men in industrialized countries. The human androgen-dependent prostate cancer cell line LNCaP, which is derived from a metastatic lesion of human prostatic adenocarcinoma, is frequently used to
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Prostate cancer is the most common malignancy, accounting for about 25% of all incident cases among men in industrialized countries. The human androgen-dependent prostate cancer cell line LNCaP, which is derived from a metastatic lesion of human prostatic adenocarcinoma, is frequently used to study prostate cancer associated signaling pathways in vitro. Recently it was described that Rho GTPase activation in these cells leads to apoptotic responses. We used the bacterial toxins CNFy and CNF1, which specifically and directly activate Rho GTPases by deamidation of a single glutamine. We asked whether these Rho activators could induce apoptosis in LNCaP cells. Our results indicate that RhoA activation, induced by CNFy, does lead to intrinsic apoptosis of the cells. Analysis of the underlying signaling pathway reveals that apoptosis induction requires the activity of Rho kinase (ROCK) and myosin activation, an apoptotic pathway previously identified in cancer stem cells. Full article
(This article belongs to the Special Issue Cytotoxic Necrotizing Factors)
Open AccessArticle Correlation of ATP Citrate Lyase and Acetyl CoA Levels with Trichothecene Production in Fusarium graminearum
Toxins 2013, 5(11), 2258-2269; doi:10.3390/toxins5112258
Received: 1 November 2013 / Revised: 18 November 2013 / Accepted: 18 November 2013 / Published: 21 November 2013
Cited by 4 | PDF Full-text (405 KB) | HTML Full-text | XML Full-text
Abstract
The correlation of ATP citrate lyase (ACL) and acetyl CoA levels with trichothecene production in Fusarium graminearum was investigated using an inhibitor (precocene II) and an enhancer (cobalt chloride) of trichothecene production by changing carbon sources in liquid medium. When precocene II (30
[...] Read more.
The correlation of ATP citrate lyase (ACL) and acetyl CoA levels with trichothecene production in Fusarium graminearum was investigated using an inhibitor (precocene II) and an enhancer (cobalt chloride) of trichothecene production by changing carbon sources in liquid medium. When precocene II (30 µM) was added to inhibit trichothecene production in a trichothecene high-production medium containing sucrose, ACL expression was reduced and ACL mRNA level as well as acetyl CoA amount in the fungal cells were reduced to the levels observed in a trichothecene trace-production medium containing glucose or fructose. The ACL mRNA level was greatly increased by addition of cobalt chloride in the trichothecene high-production medium, but not in the trichothecene trace-production medium. Levels were reduced to those level in the trichothecene trace-production medium by addition of precocene II (300 µM) together with cobalt chloride. These results suggest that ACL expression is activated in the presence of sucrose and that acetyl CoA produced by the increased ALC level may be used for trichothecene production in the fungus. These findings also suggest that sucrose is important for the action of cobalt chloride in activating trichothecene production and that precocene II may affect a step down-stream of the target of cobalt chloride. Full article
(This article belongs to the Special Issue Recent Advances and Perspectives in Deoxynivalenol Research)
Open AccessArticle The Expression of Type-1 and Type-2 Nitric Oxide Synthase in Selected Tissues of the Gastrointestinal Tract during Mixed Mycotoxicosis
Toxins 2013, 5(11), 2281-2292; doi:10.3390/toxins5112281
Received: 11 October 2013 / Revised: 12 November 2013 / Accepted: 18 November 2013 / Published: 22 November 2013
Cited by 9 | PDF Full-text (943 KB) | HTML Full-text | XML Full-text
Abstract
The aim of the study was to verify the hypothesis that intoxication with low doses of mycotoxins leads to changes in the mRNA expression levels of nitric oxide synthase-1 and nitric oxide synthase-2 genes in tissues of the gastrointestinal tract and the
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The aim of the study was to verify the hypothesis that intoxication with low doses of mycotoxins leads to changes in the mRNA expression levels of nitric oxide synthase-1 and nitric oxide synthase-2 genes in tissues of the gastrointestinal tract and the liver. The experiment involved four groups of immature gilts (with body weight of up to 25 kg) which were orally administered zearalenone in a daily dose of 40 μg/kg BW (group Z, n = 18), deoxynivalenol at 12 μg/kg BW (group D, n = 18), zearalenone and deoxynivalenol (group M, n = 18) or placebo (group C, n = 21) over a period of 42 days. The lowest mRNA expression levels of nitric oxide synthase-1 and nitric oxide synthase-2 genes were noted in the sixth week of the study, in particular in group M. Our results suggest that the presence of low mycotoxin doses in feed slows down the mRNA expression of both nitric oxide synthase isomers, which probably lowers the concentrations of nitric oxide, a common precursor of inflammation. Full article
(This article belongs to the Special Issue Recent Advances and Perspectives in Deoxynivalenol Research)

Review

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Open AccessReview Deleterious Effects of Mycotoxin Combinations Involving Ochratoxin A
Toxins 2013, 5(11), 1965-1987; doi:10.3390/toxins5111965
Received: 24 August 2013 / Revised: 24 October 2013 / Accepted: 28 October 2013 / Published: 1 November 2013
Cited by 19 | PDF Full-text (304 KB) | HTML Full-text | XML Full-text
Abstract
Ochratoxin A (OTA) is a nephrotoxic mycotoxin with carcinogenic properties. Its presence was detected in various foodstuffs all over the world but with significantly higher frequency and concentrations in areas with endemic nephropathy (EN). Even though food is often contaminated with more than
[...] Read more.
Ochratoxin A (OTA) is a nephrotoxic mycotoxin with carcinogenic properties. Its presence was detected in various foodstuffs all over the world but with significantly higher frequency and concentrations in areas with endemic nephropathy (EN). Even though food is often contaminated with more than one mycotoxin, earlier studies focused on the occurrence and toxicology of only OTA. Only a limited number of surveys showed that OTA co-occurs in food with mycotoxins (citrinin-CIT, penicilic acid, fumonisin B1-FB1, aflatoxins-AF) which exert nephrotoxic, carcinogenic or carcinogen-promoting activity. This review summarises the findings on OTA and its co-occurrence with the mentioned mycotoxins in food as well as experimental data on their combined toxicity. Most of the tested mycotoxin mixtures involving OTA produced additive or synergistic effects in experimental models suggesting that these combinations represent a significant health hazard. Special attention should be given to mixtures that include carcinogenic and cancer-promoting mycotoxins. Full article
(This article belongs to the Special Issue Recent Advances in Ochratoxins Research)
Open AccessReview Aptamers: A Promising Tool for Ochratoxin A Detection in Food Analysis
Toxins 2013, 5(11), 1988-2008; doi:10.3390/toxins5111988
Received: 25 August 2013 / Revised: 24 October 2013 / Accepted: 28 October 2013 / Published: 5 November 2013
Cited by 35 | PDF Full-text (238 KB) | HTML Full-text | XML Full-text
Abstract
The contamination of food and feed by mycotoxins has become an increasingly serious problem. Mycotoxins represent a major risk to human and animal health, as well as economics. Herein, we focus on Ochratoxin A (OTA), which is one of the most common mycotoxins
[...] Read more.
The contamination of food and feed by mycotoxins has become an increasingly serious problem. Mycotoxins represent a major risk to human and animal health, as well as economics. Herein, we focus on Ochratoxin A (OTA), which is one of the most common mycotoxins contaminating feed and foodstuffs. OTA is a secondary metabolite produced by various Aspergillus and Penicillium strains. Upon ingestion, OTA has a number of acute and chronic toxic effects. It is nephrotoxic, teratogenic, immunosuppressive, and carcinogenic (group 2B). As a consequence, some regulatory limits have been introduced on the levels of OTA in several commodities. The toxic nature of OTA demands highly sensitive and selective monitoring techniques to protect human and animal health. As alternative to traditional analytical techniques, biochemical methods for OTA analysis have attained great interest in the last few decades. They are mainly based on the integration of antibodies or aptamers as biorecognition elements in sensing platforms. However, aptamers have gained more attention in affinity-based assays because of their high affinity, specificity, stability, and their easy chemical synthesis. In this brief review, we present an overview of aptamer-based assays and their applications in OTA purification and detection, appeared in the literature in the last five years. Full article
(This article belongs to the Special Issue Recent Advances in Ochratoxins Research)
Open AccessReview Antibacterial and Antidiarrheal Activities of Plant Products against Enterotoxinogenic Escherichia coli
Toxins 2013, 5(11), 2009-2041; doi:10.3390/toxins5112009
Received: 17 September 2013 / Revised: 25 October 2013 / Accepted: 30 October 2013 / Published: 7 November 2013
Cited by 8 | PDF Full-text (663 KB) | HTML Full-text | XML Full-text
Abstract
Enterotoxigenic Escherichia coli (ETEC) produces two types of enterotoxins: heat-labile (LT) and heat-stable (STa and STb). These molecules are involved in the induction of secretory diarrhea in animals including humans. This condition is currently treated using a fluid replacement therapy and antibiotics. This
[...] Read more.
Enterotoxigenic Escherichia coli (ETEC) produces two types of enterotoxins: heat-labile (LT) and heat-stable (STa and STb). These molecules are involved in the induction of secretory diarrhea in animals including humans. This condition is currently treated using a fluid replacement therapy and antibiotics. This treatment is often not available to people in developing countries, and several die from the condition provoke by ETEC. Over the years, plants and plant extracts have been use as traditional medicine to treat various gastrointestinal ailments including diarrhea. Many of these plant products have been claimed to be active against diarrhea, however few have been extensively studied. The main objective of this review was to gather the scattered information on the antidiarrheal activities reported for various plant products on ETEC. This includes two major effects: (1) The inhibitory effect on bacterial growth or viability and (2) The interference with ETEC enterotoxins activity upon the intestinal epithelium. We will focus on plant products and extracts for which we have major indications of their biological activity against ETEC and their enterotoxins. Because Vibrio cholerae toxin (CT) is structurally, antigenically and mechanistically related to LT, it will also be discussed in this review. Full article
Figures

Open AccessReview From the Gastrointestinal Tract (GIT) to the Kidneys: Live Bacterial Cultures (Probiotics) Mediating Reductions of Uremic Toxin Levels via Free Radical Signaling
Toxins 2013, 5(11), 2042-2057; doi:10.3390/toxins5112042
Received: 2 September 2013 / Revised: 4 November 2013 / Accepted: 4 November 2013 / Published: 7 November 2013
Cited by 17 | PDF Full-text (253 KB) | HTML Full-text | XML Full-text
Abstract
A host of compounds are retained in the body of uremic patients, as a consequence of progressive renal failure. Hundreds of compounds have been reported to be retention solutes and many have been proven to have adverse biological activity, and recognized as uremic
[...] Read more.
A host of compounds are retained in the body of uremic patients, as a consequence of progressive renal failure. Hundreds of compounds have been reported to be retention solutes and many have been proven to have adverse biological activity, and recognized as uremic toxins. The major mechanistic overview considered to contribute to uremic toxin overload implicates glucotoxicity, lipotoxicity, hexosamine, increased polyol pathway activity and the accumulation of advanced glycation end-products (AGEs). Until recently, the gastrointestinal tract (GIT) and its associated micro-biometabolome was a neglected factor in chronic disease development. A systematic underestimation has been to undervalue the contribution of GIT dysbiosis (a gut barrier-associated abnormality) whereby low-level pro-inflammatory processes contribute to chronic kidney disease (CKD) development. Gut dysbiosis provides a plausible clue to the origin of systemic uremic toxin loads encountered in clinical practice and may explain the increasing occurrence of CKD. In this review, we further expand a hypothesis that posits that environmentally triggered and maintained microbiome perturbations drive GIT dysbiosis with resultant uremia. These subtle adaptation responses by the GIT microbiome can be significantly influenced by probiotics with specific metabolic properties, thereby reducing uremic toxins in the gut. The benefit translates to a useful clinical treatment approach for patients diagnosed with CKD. Furthermore, the role of reactive oxygen species (ROS) in different anatomical locales is highlighted as a positive process. Production of ROS in the GIT by the epithelial lining and the commensal microbe cohort is a regulated process, leading to the formation of hydrogen peroxide which acts as an essential second messenger required for normal cellular homeostasis and physiological function. Whilst this critical review has focused on end-stage CKD (type 5), our aim was to build a plausible hypothesis for the administration of probiotics with or without prebiotics for the early treatment of kidney disease. We postulate that targeting healthy ROS production in the gut with probiotics may be more beneficial than any systemic antioxidant therapy (that is proposed to nullify ROS) for the prevention of kidney disease progression. The study and understanding of health-promoting probiotic bacteria is in its infancy; it is complex and intellectually and experimentally challenging. Full article
(This article belongs to the Special Issue Uremic Toxins)
Open AccessReview Risk Assessment of Shellfish Toxins
Toxins 2013, 5(11), 2109-2137; doi:10.3390/toxins5112109
Received: 19 September 2013 / Revised: 23 October 2013 / Accepted: 30 October 2013 / Published: 11 November 2013
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Abstract
Complex secondary metabolites, some of which are highly toxic to mammals, are produced by many marine organisms. Some of these organisms are important food sources for marine animals and, when ingested, the toxins that they produce may be absorbed and stored in the
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Complex secondary metabolites, some of which are highly toxic to mammals, are produced by many marine organisms. Some of these organisms are important food sources for marine animals and, when ingested, the toxins that they produce may be absorbed and stored in the tissues of the predators, which then become toxic to animals higher up the food chain. This is a particular problem with shellfish, and many cases of poisoning are reported in shellfish consumers each year. At present, there is no practicable means of preventing uptake of the toxins by shellfish or of removing them after harvesting. Assessment of the risk posed by such toxins is therefore required in order to determine levels that are unlikely to cause adverse effects in humans and to permit the establishment of regulatory limits in shellfish for human consumption. In the present review, the basic principles of risk assessment are described, and the progress made toward robust risk assessment of seafood toxins is discussed. While good progress has been made, it is clear that further toxicological studies are required before this goal is fully achieved. Full article
(This article belongs to the collection Marine and Freshwater Toxins)
Open AccessReview Clostridium perfringens Epsilon Toxin: A Malevolent Molecule for Animals and Man?
Toxins 2013, 5(11), 2138-2160; doi:10.3390/toxins5112138
Received: 1 October 2013 / Revised: 30 October 2013 / Accepted: 31 October 2013 / Published: 12 November 2013
Cited by 17 | PDF Full-text (334 KB) | HTML Full-text | XML Full-text
Abstract
Clostridium perfringens is a prolific, toxin-producing anaerobe causing multiple diseases in humans and animals. One of these toxins is epsilon, a 33 kDa protein produced by Clostridium perfringens (types B and D) that induces fatal enteric disease of goats, sheep and cattle. Epsilon
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Clostridium perfringens is a prolific, toxin-producing anaerobe causing multiple diseases in humans and animals. One of these toxins is epsilon, a 33 kDa protein produced by Clostridium perfringens (types B and D) that induces fatal enteric disease of goats, sheep and cattle. Epsilon toxin (Etx) belongs to the aerolysin-like toxin family. It contains three distinct domains, is proteolytically-activated and forms oligomeric pores on cell surfaces via a lipid raft-associated protein(s). Vaccination controls Etx-induced disease in the field. However, therapeutic measures are currently lacking. This review initially introduces C. perfringens toxins, subsequently focusing upon the Etx and its biochemistry, disease characteristics in various animals that include laboratory models (in vitro and in vivo), and finally control mechanisms (vaccines and therapeutics). Full article
Open AccessReview Cytotoxic Necrotizing Factor 1 Contributes to Escherichia coli Meningitis
Toxins 2013, 5(11), 2270-2280; doi:10.3390/toxins5112270
Received: 1 October 2013 / Revised: 13 November 2013 / Accepted: 18 November 2013 / Published: 22 November 2013
Cited by 3 | PDF Full-text (413 KB) | HTML Full-text | XML Full-text
Abstract
E. coli is the most common Gram-negative bacteria causing neonatal meningitis, and E. coli meningitis continues to be an important cause of mortality and morbidity throughout the world. Recent reports of E. coli meningitis caused by antimicrobial resistant strains are a particular concern.
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E. coli is the most common Gram-negative bacteria causing neonatal meningitis, and E. coli meningitis continues to be an important cause of mortality and morbidity throughout the world. Recent reports of E. coli meningitis caused by antimicrobial resistant strains are a particular concern. These findings indicate that a novel strategy is needed to identify new targets for prevention and therapy of E. coli meningitis. Cytotoxic necrotizing factor 1 (CNF1) is a bacterial virulence factor associated principally with E. coli strains causing urinary tract infection and meningitis. We have shown that CNF1 contributes to E. coli invasion of the blood-brain barrier and penetration into the brain, the essential step in the development of E. coli meningitis, and identified the host receptor for CNF1, 37-kDa laminin receptor precursor (37LRP). CNF1, however, is a cytoplasmic protein and its contribution to E. coli invasion of the blood-brain barrier requires its secretion from the bacterial cytoplasm. No signal peptide is found in the CNF1 sequence. CNF1 secretion is, therefore, a strategy utilized by meningitis-causing E. coli to invade the blood-brain barrier. Elucidation of the mechanisms involved in CNF1 secretion, as shown in this report with the involvement of Fdx and YgfZ provides the novel information on potential targets for prevention and therapy of E. coli meningitis by virtue of targeting the secretion of CNF1. Full article
(This article belongs to the Special Issue Cytotoxic Necrotizing Factors)

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Open AccessComment The Deciphered Genome of Mesobuthus martensii Uncovers the Resistance Mysteries of Scorpion to Its Own Venom and Toxins at the Ion Channel Level
Toxins 2013, 5(11), 2209-2211; doi:10.3390/toxins5112209
Received: 4 November 2013 / Accepted: 13 November 2013 / Published: 18 November 2013
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Abstract Scorpions are amongst the most ancient arthropods, as the oldest fossils were dated from the late silurian (Proscorpius osborni, 418 million years B.P.) Full article
(This article belongs to the Section Animal Venoms)

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