Toxins

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Open AccessArticle

Aflatoxin B₁ Degradation by a Pseudomonas Strain

by Lancine Sangare, Yueju Zhao, Yawa Minnie Elodie Folly, Jinghua Chang, Jinhan Li, Jonathan Nimal Selvaraj, Fuguo Xing, Lu Zhou, Yan Wang and Yang Liu

Toxins 2014, 6(10), 3028-3040; https://doi.org/10.3390/toxins6103028 - 23 Oct 2014

Cited by 109 | Viewed by 9076 | Correction

Abstract

Aflatoxin B₁ (AFB₁), one of the most potent naturally occurring mutagens and carcinogens, causes significant threats to the food industry and animal production. In this study, 25 bacteria isolates were collected from grain kernels and soils displaying AFB₁ reduction [...] Read more.

Aflatoxin B₁ (AFB₁), one of the most potent naturally occurring mutagens and carcinogens, causes significant threats to the food industry and animal production. In this study, 25 bacteria isolates were collected from grain kernels and soils displaying AFB₁ reduction activity. Based on its degradation effectiveness, isolate N17-1 was selected for further characterization and identified as Pseudomonas aeruginosa. P. aeruginosa N17-1 could degrade AFB₁, AFB₂ and AFM₁ by 82.8%, 46.8% and 31.9% after incubation in Nutrient Broth (NB) medium at 37 °C for 72 h, respectively. The culture supernatant of isolate N17-1 degraded AFB₁ effectively, whereas the viable cells and intra cell extracts were far less effective. Factors influencing AFB₁ degradation by the culture supernatant were investigated. Maximum degradation was observed at 55 °C. Ions Mn²⁺ and Cu²⁺ were activators for AFB₁ degradation, however, ions Mg²⁺, Li⁺, Zn²⁺, Se²⁺, Fe³⁺ were strong inhibitors. Treatments with proteinase K and proteinase K plus SDS significantly reduced the degradation activity of the culture supernatant. No degradation products were observed based on preliminary LC-QTOF/MS analysis, indicating AFB₁ was metabolized to degradation products with chemical properties different from that of AFB₁. The results indicated that the degradation of AFB₁ by P. aeruginosa N17-1 was enzymatic and could have a great potential in industrial applications. This is the first report indicating that the isolate of P. aeruginosa possesses the ability to degrade aflatoxin. Full article

(This article belongs to the Special Issue Detoxification of Mycotoxins)

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790 KiB

Open AccessReview

Bt Toxin Modification for Enhanced Efficacy

by Benjamin R. Deist, Michael A. Rausch, Maria Teresa Fernandez-Luna, Michael J. Adang and Bryony C. Bonning

Toxins 2014, 6(10), 3005-3027; https://doi.org/10.3390/toxins6103005 - 22 Oct 2014

Cited by 60 | Viewed by 14783

Abstract

Insect-specific toxins derived from Bacillus thuringiensis (Bt) provide a valuable resource for pest suppression. Here we review the different strategies that have been employed to enhance toxicity against specific target species including those that have evolved resistance to Bt, or to modify the [...] Read more.

Insect-specific toxins derived from Bacillus thuringiensis (Bt) provide a valuable resource for pest suppression. Here we review the different strategies that have been employed to enhance toxicity against specific target species including those that have evolved resistance to Bt, or to modify the host range of Bt crystal (Cry) and cytolytic (Cyt) toxins. These strategies include toxin truncation, modification of protease cleavage sites, domain swapping, site-directed mutagenesis, peptide addition, and phage display screens for mutated toxins with enhanced activity. Toxin optimization provides a useful approach to extend the utility of these proteins for suppression of pests that exhibit low susceptibility to native Bt toxins, and to overcome field resistance. Full article

(This article belongs to the Special Issue Bacillus thuringiensis Toxins)

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Graphical abstract

343 KiB

Open AccessCommunication

Efficacy of Active Carbon towards the Absorption of Deoxynivalenol in Pigs

by Mathias Devreese, Gunther Antonissen, Patrick De Backer and Siska Croubels

Toxins 2014, 6(10), 2998-3004; https://doi.org/10.3390/toxins6102998 - 21 Oct 2014

Cited by 30 | Viewed by 5683

Abstract

In order to assess the in vivo efficacy of mycotoxin binders, specific toxicokinetic parameters should be measured according to European guidelines. For this purpose, an absorption model in pigs is described with emphasis on absorption kinetics. Pigs received a single oral bolus of [...] Read more.

In order to assess the in vivo efficacy of mycotoxin binders, specific toxicokinetic parameters should be measured according to European guidelines. For this purpose, an absorption model in pigs is described with emphasis on absorption kinetics. Pigs received a single oral bolus of the mycotoxin deoxynivalenol alone or in combination with active carbon (applied as mycotoxin binder). After administration of deoxynivalenol alone, significant plasma amounts of deoxynivalenol were detected and kinetic parameters were calculated using a one compartmental model. Activated carbon completely prevented the absorption of deoxynivalenol as no plasma amounts could be detected. Full article

(This article belongs to the Special Issue Detoxification of Mycotoxins)

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Open AccessReview

Epidemiology and Clinical Features of Ciguatera Fish Poisoning in Hong Kong

by Thomas Y. K. Chan

Toxins 2014, 6(10), 2989-2997; https://doi.org/10.3390/toxins6102989 - 20 Oct 2014

Cited by 22 | Viewed by 8335

Abstract

In the present review, the main objective was to describe the epidemiology and clinical features of ciguatera fish poisoning in Hong Kong. From 1989 to 2008, the annual incidence of ciguatera varied between 3.3 and 64.9 (median 10.2) per million people. The groupers [...] Read more.

In the present review, the main objective was to describe the epidemiology and clinical features of ciguatera fish poisoning in Hong Kong. From 1989 to 2008, the annual incidence of ciguatera varied between 3.3 and 64.9 (median 10.2) per million people. The groupers have replaced the snappers as the most important cause of ciguatera. Pacific-ciguatoxins (CTX) are most commonly present in reef fish samples implicated in ciguatera outbreaks. In affected subjects, the gastrointestinal symptoms often subside within days, whereas the neurological symptoms can persist for weeks or even months. Bradycardia and hypotension, which can be life-threatening, are common. Treatment of ciguatera is primarily supportive and symptomatic. Intravenous mannitol (1 g/kg) has also been suggested. To prevent ciguatera outbreaks, the public should be educated to avoid eating large coral reef fishes, especially the CTX-rich parts. A Code of Practice on Import and Sale of Live Marine Fish for Human Consumption for Prevention and Control of Ciguatera Fish Poisoning was introduced from 2004 to 2013. The Food Safety Ordinance with a tracing mechanism came into full effect in February 2012. The Government would be able to trace the sources of the fishes more effectively and take prompt action when dealing with ciguatera incidents. Full article

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

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Open AccessArticle

Piperlongumine-Induced Phosphatidylserine Translocation in the Erythrocyte Membrane

by Rosi Bissinger, Abaid Malik, Jamshed Warsi, Kashif Jilani and Florian Lang

Toxins 2014, 6(10), 2975-2988; https://doi.org/10.3390/toxins6102975 - 14 Oct 2014

Cited by 6 | Viewed by 5957

Abstract

Background: Piperlongumine, a component of Piper longum fruit, is considered as a treatment for malignancy. It is effective by inducing apoptosis. Mechanisms involved in the apoptotic action of piperlongumine include oxidative stress and activation of p38 kinase. In analogy to apoptosis of [...] Read more.

Background: Piperlongumine, a component of Piper longum fruit, is considered as a treatment for malignancy. It is effective by inducing apoptosis. Mechanisms involved in the apoptotic action of piperlongumine include oxidative stress and activation of p38 kinase. In analogy to apoptosis of nucleated cells, erythrocytes may undergo eryptosis, the suicidal death of erythrocytes characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine-exposure at the erythrocyte surface. Signaling involved in eryptosis include increase of cytosolic Ca²⁺-activity ([Ca²⁺]_i), formation of ceramide, oxidative stress and activation of p38 kinase. Methods: Cell volume was estimated from forward scatter, phosphatidylserine-exposure from annexin V binding, [Ca²⁺]_i from Fluo3 fluorescence, reactive oxygen species from 2',7'-dichlorodihydrofluorescein-diacetate fluorescence, and ceramide abundance from binding of fluorescent antibodies in flow cytometry. Results: A 48 h exposure to piperlongumine (30 µM) was followed by significant decrease of forward scatter and increase of annexin-V-binding. Piperlongumine did not significantly modify [Ca²⁺]_i and the effect was not dependent on presence of extracellular Ca²⁺. Piperlongumine significantly increased ROS formation and ceramide abundance. Conclusions: Piperlongumine triggers cell membrane scrambling, an effect independent from entry of extracellular Ca²⁺ but at least partially due to ROS and ceramide formation. Full article

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Open AccessArticle

Milk Thistle Extract and Silymarin Inhibit Lipopolysaccharide Induced Lamellar Separation of Hoof Explants in Vitro

by Nicole Reisinger, Simone Schaumberger, Veronika Nagl, Sabine Hessenberger and Gerd Schatzmayr

Toxins 2014, 6(10), 2962-2974; https://doi.org/10.3390/toxins6102962 - 6 Oct 2014

Cited by 19 | Viewed by 7539

Abstract

The pathogenesis of laminitis is not completely identified and the role of endotoxins (lipopolysaccharides, LPS) in this process remains unclear. Phytogenic substances, like milk thistle (MT) and silymarin, are known for their anti-inflammatory and antioxidant properties and might therefore have the potential to [...] Read more.

The pathogenesis of laminitis is not completely identified and the role of endotoxins (lipopolysaccharides, LPS) in this process remains unclear. Phytogenic substances, like milk thistle (MT) and silymarin, are known for their anti-inflammatory and antioxidant properties and might therefore have the potential to counteract endotoxin induced effects on the hoof lamellar tissue. The aim of our study was to investigate the influence of endotoxins on lamellar tissue integrity and to test if MT and silymarin are capable of inhibiting LPS-induced effects in an in vitro/ex vivo model. In preliminary tests, LPS neutralization efficiency of these phytogenics was determined in an in vitro neutralization assay. Furthermore, tissue explants gained from hooves of slaughter horses were tested for lamellar separation after incubation with different concentrations of LPS. By combined incubation of explants with LPS and either Polymyxin B (PMB; positive control), MT or silymarin, the influence of these substances on LPS-induced effects was assessed. In the in vitro neutralization assay, MT and silymarin reduced LPS concentrations by 64% and 75%, respectively, in comparison PMB reduced 98% of the LPS concentration. In hoof explants, LPS led to a concentration dependent separation. Accordantly, separation force was significantly decreased by 10 µg/mL LPS. PMB, MT and silymarin could significantly improve tissue integrity of explants incubated with 10 µg/mL LPS. This study showed that LPS had a negative influence on the structure of hoof explants in vitro. MT and silymarin reduced endotoxin activity and inhibited LPS-induced effects on the lamellar tissue. Hence, MT and silymarin might be used to support the prevention of laminitis and should be further evaluated for this application. Full article

(This article belongs to the Section Bacterial Toxins)

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1165 KiB

Open AccessArticle

Toxins VapC and PasB from Prokaryotic TA Modules Remain Active in Mammalian Cancer Cells

by Łukasz Wieteska, Aleksander Skulimowski, Magdalena Cybula and Janusz Szemraj

Toxins 2014, 6(10), 2948-2961; https://doi.org/10.3390/toxins6102948 - 30 Sep 2014

Cited by 8 | Viewed by 6359

Abstract

Among the great number of addictive modules which have been discovered, only a few have been characterized. However, research concerning the adoption of toxins from these systems shows their great potential as a tool for molecular biology and medicine. In our study, we [...] Read more.

Among the great number of addictive modules which have been discovered, only a few have been characterized. However, research concerning the adoption of toxins from these systems shows their great potential as a tool for molecular biology and medicine. In our study, we tested two different toxins derived from class II addictive modules, pasAB from plasmid pTF-FC2 (Thiobacillus ferrooxidans) and vapBC 2829Rv (Mycobacterium tuberculosis), in terms of their usefulness as growth inhibitors of human cancer cell lines, namely KYSE 30, MCF-7 and HCT 116. Transfection of the pasB and vapC genes into the cells was conducted with the use of two different expression systems. Cellular effects, such as apoptosis, necrosis and changes in the cell cycle, were tested by applying flow cytometry with immunofluorescence staining. Our findings demonstrated that toxins VapC and PasB demonstrate proapoptotic activity in the human cancer cells, regardless of the expression system used. As for the toxin PasB, observed changes were more subtle than for the VapC. The level of expression for both the genes was monitored by QPCR and did not reveal statistically significant differences within the same cell line. Full article

(This article belongs to the Section Bacterial Toxins)

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Open AccessArticle

Nitrogen Limitation Promotes Accumulation and Suppresses Release of Cylindrospermopsins in Cells of Aphanizomenon Sp.

by Karina Preußel, Ingrid Chorus and Jutta Fastner

Toxins 2014, 6(10), 2932-2947; https://doi.org/10.3390/toxins6102932 - 30 Sep 2014

Cited by 18 | Viewed by 7147

Abstract

As the biosynthesis of cylindrospermopsin (CYN) is assumed to depend on nitrogen availability, this study investigated the impact of nitrogen availability on intra- and extracellular CYN and deoxy-CYN (D-CYN) contents in three Aphanizomenon strains from temperate waters. Nitrogen deficient (−N) cultures showed a [...] Read more.

As the biosynthesis of cylindrospermopsin (CYN) is assumed to depend on nitrogen availability, this study investigated the impact of nitrogen availability on intra- and extracellular CYN and deoxy-CYN (D-CYN) contents in three Aphanizomenon strains from temperate waters. Nitrogen deficient (−N) cultures showed a prolonged growth phase and intracellular toxin accumulation by a factor of 2–6. In contrast, cultures with additional nitrate supply (+N) did not accumulate CYN within the cells. Instead, the maximum conceivable CYN release estimated for dead cells (identified by SYTOX^® Green staining) was much lower than the concentrations of dissolved CYN actually observed, suggesting these cultures actively release CYN from intact cells. Furthermore, we found remarkably altered proportions of CYN to D-CYN: as batch cultures grew, the proportion of D-CYN increased by up to 40% in +N medium, whereas D-CYN remained constant or decreased slightly in −N medium. Since +N cultures showed similar toxin patterns as −P cultures with increased extracellular CYNs and higher proportion of D-CYN we conclude that nitrogen limitation may affect the way the cells economize resources, especially the yield from phosphorus pools, and that this has an impact on CYN production and release. For water management, these result imply that nutrient availability not only determines the abundance of potentially CYN-producing cyanobacteria, but also the amount of extracellular CYNs (challenging drinking-water treatment) as well as the ratio of D-CYN to CYN (affecting toxicity). Full article

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

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Open AccessArticle

Presence of Potential Toxin-Producing Cyanobacteria in an Oligo-Mesotrophic Lake in Baltic Lake District, Germany: An Ecological, Genetic and Toxicological Survey

by Pawan K. Dadheech, Géza B. Selmeczy, Gábor Vasas, Judit Padisák, Wolfgang Arp, Kálmán Tapolczai, Peter Casper and Lothar Krienitz

Toxins 2014, 6(10), 2912-2931; https://doi.org/10.3390/toxins6102912 - 29 Sep 2014

Cited by 21 | Viewed by 6947

Abstract

Massive developments of potentially toxic cyanobacteria in Lake Stechlin, an oligo-mesotrophic lake in the Baltic Lake District of Germany raised concerns about toxic contamination of these important ecosystems. Field samples in the phase of mass developments of cyanobacteria were used for genetic and [...] Read more.

Massive developments of potentially toxic cyanobacteria in Lake Stechlin, an oligo-mesotrophic lake in the Baltic Lake District of Germany raised concerns about toxic contamination of these important ecosystems. Field samples in the phase of mass developments of cyanobacteria were used for genetic and toxicological analyses. Microcystins and microcystin genes were detected in field samples of the lake for the first time. However, the toxins were not produced by the dominant taxa (Dolichospermum circinale and Aphanizomenon flos-aquae) but by taxa, which were present only in low biomass in the samples (Microcystis cf. aeruginosa and Planktothrix rubescens). The phytoplankton successions during the study period revealed an increase of cyanobacterial populations. The findings contribute to the changes that have been investigated in Lake Stechlin since the mid-1990s. The possible reasons behind these developments may be climate change, special weather conditions and an increased nutrient pool. Full article

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

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Open AccessArticle

Non-Native (Exotic) Snake Envenomations in the U.S., 2005–2011

by Brandon J. Warrick, Leslie V. Boyer and Steven A. Seifert

Toxins 2014, 6(10), 2899-2911; https://doi.org/10.3390/toxins6102899 - 29 Sep 2014

Cited by 31 | Viewed by 7681

Abstract

Non-native (exotic) snakes are a problematic source of envenomation worldwide. This manuscript describes the current demographics, outcomes and challenges of non-native snakebites in the United States (U.S.). We performed a retrospective case series of the National Poison Data System (NPDS) database between 2005 [...] Read more.

Non-native (exotic) snakes are a problematic source of envenomation worldwide. This manuscript describes the current demographics, outcomes and challenges of non-native snakebites in the United States (U.S.). We performed a retrospective case series of the National Poison Data System (NPDS) database between 2005 and 2011. There were 258 human exposures involving at least 61 unique exotic venomous species (average = 37 per year; range = 33–40). Males comprised 79% and females 21%. The average age was 33 years with 16% less than 20 years old. 70% of bites occurred in a private residence and 86% were treated at a healthcare facility. 35% of cases received antivenom and 10% were given antibiotics. This study is compared to our previous study (1994–2004) in which there was a substantial coding error rate. Software modifications significantly reduced coding errors. Identification and acquisition of appropriate antivenoms pose a number of logistical difficulties in the management of these envenomations. In the U.S., poison centers have valuable systems and clinical roles in the provision of expert consultation and in the management of these cases. Full article

(This article belongs to the Special Issue Antivenom and Venom Therapeutics)

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Open AccessArticle

A Novel Bradykinin-Related Dodecapeptide (RVALPPGFTPLR) from the Skin Secretion of the Fujian Large-Headed Frog (Limnonectes fujianensis) Exhibiting Unusual Structural and Functional Features

by Daning Shi, Yu Luo, Qiang Du, Lei Wang, Mei Zhou, Jie Ma, Renjie Li, Tianbao Chen and Chris Shaw

Toxins 2014, 6(10), 2886-2898; https://doi.org/10.3390/toxins6102886 - 29 Sep 2014

Cited by 7 | Viewed by 5349

Abstract

Bradykinin-related peptides (BRPs) are significant components of the defensive skin secretions of many anuran amphibians, and these secretions represent the source of the most diverse spectrum of such peptides so far encountered in nature. Of the many families of bioactive peptides that have [...] Read more.

Bradykinin-related peptides (BRPs) are significant components of the defensive skin secretions of many anuran amphibians, and these secretions represent the source of the most diverse spectrum of such peptides so far encountered in nature. Of the many families of bioactive peptides that have been identified from this source, the BRPs uniquely appear to represent homologues of counterparts that have specific distributions and receptor targets within discrete vertebrate taxa, ranging from fishes through mammals. Their broad spectra of actions, including pain and inflammation induction and smooth muscle effects, make these peptides ideal weapons in predator deterrence. Here, we describe a novel 12-mer BRP (RVALPPGFTPLR-RVAL-(L¹, T⁶, L⁸)-bradykinin) from the skin secretion of the Fujian large-headed frog (Limnonectes fujianensis). The C-terminal 9 residues of this BRP (-LPPGFTPLR) exhibit three amino acid substitutions (L/R at Position 1, T/S at Position 6 and L/F at Position 8) when compared to canonical mammalian bradykinin (BK), but are identical to the kinin sequence present within the cloned kininogen-2 from the Chinese soft-shelled turtle (Pelodiscus sinensis) and differ from that encoded by kininogen-2 of the Tibetan ground tit (Pseudopodoces humilis) at just a single site (F/L at Position 8). These data would imply that the novel BRP is an amphibian defensive agent against predation by sympatric turtles and also that the primary structure of the avian BK, ornithokinin (RPPGFTPLR), is not invariant within this taxon. Synthetic RVAL-(L¹, T⁶, L⁸)-bradykinin was found to be an antagonist of BK-induced rat tail artery smooth muscle relaxation acting via the B₂-receptor. Full article

(This article belongs to the Section Animal Venoms)

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Open AccessArticle

Evaluation of Cytotoxicity, Genotoxicity and Hematotoxicity of the Recombinant Spore-Crystal Complexes Cry1Ia, Cry10Aa and Cry1Ba6 from Bacillus thuringiensis in Swiss Mice

by Ingrid De Souza Freire, Ana Luisa Miranda-Vilela, Lilian Carla Pereira Barbosa, Erica Soares Martins, Rose Gomes Monnerat and Cesar Koppe Grisolia

Toxins 2014, 6(10), 2872-2885; https://doi.org/10.3390/toxins6102872 - 29 Sep 2014

Cited by 9 | Viewed by 5853

Abstract

The insecticidal properties of Cry-endotoxins from Bacillus thuringiensis (Bt) have long been used as spore-crystals in commercial spray formulations for insect control. Recently, some Bt-endotoxin genes have been cloned in many different plants. Toxicological evaluations of three spore-crystal endotoxins, BtCry1Ia, BtCry10Aa and BtCry1Ba6 [...] Read more.

The insecticidal properties of Cry-endotoxins from Bacillus thuringiensis (Bt) have long been used as spore-crystals in commercial spray formulations for insect control. Recently, some Bt-endotoxin genes have been cloned in many different plants. Toxicological evaluations of three spore-crystal endotoxins, BtCry1Ia, BtCry10Aa and BtCry1Ba6 from B. thuringiensis, were carried out on mice to understand their adverse effects on hematological systems and on genetic material. These three spore-crystals have shown toxic activity to the boll weevil, which is one of the most aggressive pests of the cotton crop. Cry1Ia, Cry10Aa and Cry1Ba6 did not increase the micronucleus frequency in the peripheral erythrocytes of mice and did not cause changes in the frequency of polychromatic erythrocytes. However, some hematologic disburbances were observed, specifically related to Cry1Ia and Cry1Ba6, respectively, for the erythroid and lymphoid lineage. Thus, although the profile of such adverse side effects can be related to their high level of exposure, which is not commonly found in the environment, results showed that these Bt spore-crystals were not harmless to mice, indicating that each spore-crystal endotoxin presents a characteristic profile of toxicity and might be investigated individually. Full article

(This article belongs to the Special Issue Bacillus thuringiensis Toxins)

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Toxins, Volume 6, Issue 10 (October 2014) – 12 articles , Pages 2872-3040

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