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Toxins
Volume 7
Issue 11
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Toxins, Volume 7, Issue 11 (November 2015) – 28 articles , Pages 4390-4851

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505 KiB  
Review
Centipede Venoms and Their Components: Resources for Potential Therapeutic Applications
by Md Abdul Hakim, Shilong Yang and Ren Lai
Toxins 2015, 7(11), 4832-4851; https://doi.org/10.3390/toxins7114832 - 17 Nov 2015
Cited by 43 | Viewed by 12678
Abstract
Venomous animals have evolved with sophisticated bio-chemical strategies to arrest prey and defend themselves from natural predators. In recent years, peptide toxins from venomous animals have drawn considerable attention from researchers due to their surprising chemical, biochemical, and pharmacological diversity. Similar to other [...] Read more.
Venomous animals have evolved with sophisticated bio-chemical strategies to arrest prey and defend themselves from natural predators. In recent years, peptide toxins from venomous animals have drawn considerable attention from researchers due to their surprising chemical, biochemical, and pharmacological diversity. Similar to other venomous animals, centipedes are one of the crucial venomous arthropods that have been used in traditional medicine for hundreds of years in China. Despite signifying pharmacological importance, very little is known about the active components of centipede venoms. More than 500 peptide sequences have been reported in centipede venomous glands by transcriptome analysis, but only a small number of peptide toxins from centipede has been functionally described. Like other venomous animals such as snakes, scorpions, and spiders, the venom of centipedes could be an excellent source of peptides for developing drugs for treatments as well as bio-insecticides for agrochemical applications. Although centipede venoms are yet to be adequately studied, the venom of centipedes as well as their components described to date, should be compiled to help further research. Therefore, based on previous reports, this review focusses on findings and possible therapeutic applications of centipede venoms as well as their components. Full article
(This article belongs to the Special Issue Arthropod Venoms)
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Article
Diverse Profiles of Ricin-Cell Interactions in the Lung Following Intranasal Exposure to Ricin
by Anita Sapoznikov, Reut Falach, Ohad Mazor, Ron Alcalay, Yoav Gal, Nehama Seliger, Tamar Sabo and Chanoch Kronman
Toxins 2015, 7(11), 4817-4831; https://doi.org/10.3390/toxins7114817 - 17 Nov 2015
Cited by 34 | Viewed by 5080
Abstract
Ricin, a plant-derived exotoxin, inhibits protein synthesis by ribosomal inactivation. Due to its wide availability and ease of preparation, ricin is considered a biothreat, foremost by respiratory exposure. We examined the in vivo interactions between ricin and cells of the lungs in mice [...] Read more.
Ricin, a plant-derived exotoxin, inhibits protein synthesis by ribosomal inactivation. Due to its wide availability and ease of preparation, ricin is considered a biothreat, foremost by respiratory exposure. We examined the in vivo interactions between ricin and cells of the lungs in mice intranasally exposed to the toxin and revealed multi-phasic cell-type-dependent binding profiles. While macrophages (MΦs) and dendritic cells (DCs) displayed biphasic binding to ricin, monophasic binding patterns were observed for other cell types; epithelial cells displayed early binding, while B cells and endothelial cells bound toxin late after intoxication. Neutrophils, which were massively recruited to the intoxicated lung, were refractive to toxin binding. Although epithelial cells bound ricin as early as MΦs and DCs, their rates of elimination differed considerably; a reduction in epithelial cell counts occurred late after intoxication and was restricted to alveolar type II cells only. The differential binding and cell-elimination patterns observed may stem from dissimilar accessibility of the toxin to different cells in the lung and may also reflect unequal interactions of the toxin with different cell-surface receptors. The multifaceted interactions observed in this study between ricin and the various cells of the target organ should be considered in the future development of efficient post-exposure countermeasures against ricin intoxication. Full article
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Article
Botulinum Toxin Type A Induces Changes in the Chemical Coding of Substance P-Immunoreactive Dorsal Root Ganglia Sensory Neurons Supplying the Porcine Urinary Bladder
by Agnieszka Bossowska, Ewa Lepiarczyk, Urszula Mazur, Paweł Janikiewicz and Włodzimierz Markiewicz
Toxins 2015, 7(11), 4797-4816; https://doi.org/10.3390/toxins7114797 - 16 Nov 2015
Cited by 17 | Viewed by 6599
Abstract
Botulinum toxin (BTX) is a potent neurotoxin which blocks acetylcholine release from nerve terminals, and therefore leads to cessation of somatic motor and/or parasympathetic transmission. Recently it has been found that BTX also interferes with sensory transmission, thus, the present study was aimed [...] Read more.
Botulinum toxin (BTX) is a potent neurotoxin which blocks acetylcholine release from nerve terminals, and therefore leads to cessation of somatic motor and/or parasympathetic transmission. Recently it has been found that BTX also interferes with sensory transmission, thus, the present study was aimed at investigating the neurochemical characterization of substance P-immunoreactive (SP-IR) bladder-projecting sensory neurons (BPSN) after the toxin treatment. Investigated neurons were visualized with retrograde tracing method and their chemical profile was disclosed with double-labelling immunohistochemistry using antibodies against SP, calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase activating polypeptide (PACAP), neuronal nitric oxide synthase (nNOS), galanin (GAL), calbindin (CB), and somatostatin (SOM). In the control group (n = 6), 45% of the total population of BPSN were SP-IR. Nearly half of these neurons co-expressed PACAP or CGRP (45% and 35%, respectively), while co-localization of SP with GAL, nNOS, SOM or CB was found less frequently (3.7%, 1.8%, 1.2%, and 0.7%, respectively). In BTX-treated pigs (n = 6), toxin-injections caused a decrease in the number of SP-IR cells containing CGRP, SOM or CB (16.2%, 0.5%, and 0%, respectively) and a distinct increase in these nerve cells immunopositive to GAL (27.2%). The present study demonstrates that BTX significantly modifies the chemical phenotypes of SP-IR BPSN. Full article
(This article belongs to the Collection Botulinum Toxins on Human Pain)
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Article
Metabolic and Hematological Consequences of Dietary Deoxynivalenol Interacting with Systemic Escherichia coli Lipopolysaccharide
by Erik Bannert, Tanja Tesch, Jeannette Kluess, Jana Frahm, Susanne Kersten, Stefan Kahlert, Lydia Renner, Hermann-Josef Rothkötter and Sven Dänicke
Toxins 2015, 7(11), 4773-4796; https://doi.org/10.3390/toxins7114773 - 16 Nov 2015
Cited by 21 | Viewed by 4868
Abstract
Previous studies have shown that chronic oral deoxynivalenol (DON) exposure modulated Escherichia coli lipopolysaccharide (LPS)-induced systemic inflammation, whereby the liver was suspected to play an important role. Thus, a total of 41 barrows was fed one of two maize-based diets, either a DON-diet [...] Read more.
Previous studies have shown that chronic oral deoxynivalenol (DON) exposure modulated Escherichia coli lipopolysaccharide (LPS)-induced systemic inflammation, whereby the liver was suspected to play an important role. Thus, a total of 41 barrows was fed one of two maize-based diets, either a DON-diet (4.59 mg DON/kg feed, n = 19) or a control diet (CON, n = 22). Pigs were equipped with indwelling catheters for pre- or post-hepatic (portal vs. jugular catheter) infusion of either control (0.9% NaCl) or LPS (7.5 µg/kg BW) for 1h and frequent blood sampling. This design yielded six groups: CON_CONjugular‑CONportal, CON_CONjugular‑LPSportal, CON_LPSjugular‑CONportal, DON_CONjugular‑CONportal, DON_CONjugular‑LPSportal and DON_LPSjugular‑CONportal. Blood samples were analyzed for blood gases, electrolytes, glucose, pH, lactate and red hemogram. The red hemogram and electrolytes were not affected by DON and LPS. DON-feeding solely decreased portal glucose uptake (p < 0.05). LPS-decreased partial oxygen pressure (pO2) overall (p < 0.05), but reduced pCO2 only in arterial blood, and DON had no effect on either. Irrespective of catheter localization, LPS decreased pH and base-excess (p < 0.01), but increased lactate and anion-gap (p < 0.01), indicating an emerging lactic acidosis. Lactic acidosis was more pronounced in the group DON_LPSjugular-CONportal than in CON-fed counterparts (p < 0.05). DON-feeding aggravated the porcine acid-base balance in response to a subsequent immunostimulus dependent on its exposure site (pre- or post-hepatic). Full article
(This article belongs to the Special Issue Mycotoxins and Human Diseases 2015)
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Review
The Protective Effect of Bee Venom on Fibrosis Causing Inflammatory Diseases
by Woo-Ram Lee, Sok Cheon Pak and Kwan-Kyu Park
Toxins 2015, 7(11), 4758-4772; https://doi.org/10.3390/toxins7114758 - 16 Nov 2015
Cited by 45 | Viewed by 7371
Abstract
Bee venom therapy is a treatment modality that may be thousands of years old and involves the application of live bee stings to the patient’s skin or, in more recent years, the injection of bee venom into the skin with a hypodermic needle. [...] Read more.
Bee venom therapy is a treatment modality that may be thousands of years old and involves the application of live bee stings to the patient’s skin or, in more recent years, the injection of bee venom into the skin with a hypodermic needle. Studies have proven the effectiveness of bee venom in treating pathological conditions such as arthritis, pain and cancerous tumors. However, there has not been sufficient review to fully elucidate the cellular mechanisms of the anti-inflammatory effects of bee venom and its components. In this respect, the present study reviews current understanding of the mechanisms of the anti-inflammatory properties of bee venom and its components in the treatment of liver fibrosis, atherosclerosis and skin disease. Full article
(This article belongs to the Special Issue Bee and Wasp Venoms: Biological Characteristics and Therapeutic Application)
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Article
A Simple and Rapid Procedure for the Detection of Genes Encoding Shiga Toxins and Other Specific DNA Sequences
by Bożena Nejman-Faleńczyk, Sylwia Bloch, Aleksandra Januszkiewicz, Alicja Węgrzyn and Grzegorz Węgrzyn
Toxins 2015, 7(11), 4745-4757; https://doi.org/10.3390/toxins7114745 - 13 Nov 2015
Cited by 5 | Viewed by 4722
Abstract
A novel procedure for the detection of specific DNA sequences has been developed. This procedure is based on the already known method employing PCR with appropriate primers and a sequence-specific DNA probe labeled with the fluorescent agent 6-carboxylfluorescein (FAM) at the 5′ end [...] Read more.
A novel procedure for the detection of specific DNA sequences has been developed. This procedure is based on the already known method employing PCR with appropriate primers and a sequence-specific DNA probe labeled with the fluorescent agent 6-carboxylfluorescein (FAM) at the 5′ end and the fluorescence quencher BHQ-1 (black hole quencher) at the 3′ end. However, instead of the detection of the fluorescence signal with the use of real-time PCR cyclers, fluorescence/luminescence spectrometers or fluorescence polarization readers, as in all previously-reported procedures, we propose visual observation of the fluorescence under UV light directly in the reaction tube. An example for the specific detection of the Shiga toxin-producing Escherichia coli (STEC) strains, by detecting Shiga toxin genes, is demonstrated. This method appears to be specific, simple, rapid and cost effective. It may be suitable for use in research laboratories, as well as in diagnostic units of medical institutions, even those equipped only with a thermocycler and a UV transilluminator, particularly if rapid identification of a pathogen is required. Full article
(This article belongs to the Section Bacterial Toxins)
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Article
Vitamin D3 and Monomethyl Fumarate Enhance Natural Killer Cell Lysis of Dendritic Cells and Ameliorate the Clinical Score in Mice Suffering from Experimental Autoimmune Encephalomyelitis
by Zaidoon Al-Jaderi and Azzam A. Maghazachi
Toxins 2015, 7(11), 4730-4744; https://doi.org/10.3390/toxins7114730 - 13 Nov 2015
Cited by 15 | Viewed by 6341
Abstract
Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell mediated inflammatory demyelinating disease that is induced in mice by administration of peptides derived from myelin proteins. We developed EAE in SJL mice by administration of PLP139–151 peptide. The effect of treating [...] Read more.
Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell mediated inflammatory demyelinating disease that is induced in mice by administration of peptides derived from myelin proteins. We developed EAE in SJL mice by administration of PLP139–151 peptide. The effect of treating these mice with 1α,25-Dihydroxyvitamin D3 (vitamin D3), or with monomethyl fumarate (MMF) was then examined. We observed that both vitamin D3 and MMF inhibited and/or prevented EAE in these mice. These findings were corroborated with isolating natural killer (NK) cells from vitamin D3-treated or MMF-treated EAE mice that lysed immature or mature dendritic cells. The results support and extend other findings indicating that an important mechanism of action for drugs used to treat multiple sclerosis (MS) is to enhance NK cell lysis of dendritic cells. Full article
(This article belongs to the Collection Toxicity and Therapeutic Interventions in the Immune System)
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Article
Metabolism of Deoxynivalenol and Deepoxy-Deoxynivalenol in Broiler Chickens, Pullets, Roosters and Turkeys
by Heidi E. Schwartz-Zimmermann, Philipp Fruhmann, Sven Dänicke, Gerlinde Wiesenberger, Sylvia Caha, Julia Weber and Franz Berthiller
Toxins 2015, 7(11), 4706-4729; https://doi.org/10.3390/toxins7114706 - 12 Nov 2015
Cited by 48 | Viewed by 7500
Abstract
Recently, deoxynivalenol-3-sulfate (DON-3-sulfate) was proposed as a major DON metabolite in poultry. In the present work, the first LC-MS/MS based method for determination of DON-3-sulfate, deepoxy-DON-3-sulfate (DOM-3-sulfate), DON, DOM, DON sulfonates 1, 2, 3, and DOM sulfonate 2 in excreta samples of chickens [...] Read more.
Recently, deoxynivalenol-3-sulfate (DON-3-sulfate) was proposed as a major DON metabolite in poultry. In the present work, the first LC-MS/MS based method for determination of DON-3-sulfate, deepoxy-DON-3-sulfate (DOM-3-sulfate), DON, DOM, DON sulfonates 1, 2, 3, and DOM sulfonate 2 in excreta samples of chickens and turkeys was developed and validated. To this end, DOM-3-sulfate was chemically synthesized and characterized by NMR and LC-HR-MS/MS measurements. Application of the method to excreta and chyme samples of four feeding trials with turkeys, chickens, pullets, and roosters confirmed DON-3-sulfate as the major DON metabolite in all poultry species studied. Analogously to DON-3-sulfate, DOM-3-sulfate was formed after oral administration of DOM both in turkeys and in chickens. In addition, pullets and roosters metabolized DON into DOM-3-sulfate. In vitro transcription/translation assays revealed DOM-3-sulfate to be 2000 times less toxic on the ribosome than DON. Biological recoveries of DON and DOM orally administered to broiler chickens, turkeys, and pullets were 74%–106% (chickens), 51%–72% (roosters), and 131%–151% (pullets). In pullets, DON-3-sulfate concentrations increased from jejunum chyme samples to excreta samples by a factor of 60. This result, put into context with earlier studies, indicates fast and efficient absorption of DON between crop and jejunum, conversion to DON-3-sulfate in intestinal mucosa, liver, and possibly kidney, and rapid elimination into excreta via bile and urine. Full article
(This article belongs to the Collection Fusarium Toxins – Relevance for Human and Animal Health)
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Article
The Effects of Low Doses of Two Fusarium Toxins, Zearalenone and Deoxynivalenol, on the Pig Jejunum. A Light and Electron Microscopic Study
by Barbara Przybylska-Gornowicz, Michał Tarasiuk, Bogdan Lewczuk, Magdalena Prusik, Natalia Ziółkowska, Łukasz Zielonka, Maciej Gajęcki and Magdalena Gajęcka
Toxins 2015, 7(11), 4684-4705; https://doi.org/10.3390/toxins7114684 - 11 Nov 2015
Cited by 44 | Viewed by 6508
Abstract
Immature gilts were administered per os with zearalenone (ZEN) at 40 μg/kg BW (group Z, n = 9), deoxynivalenol (DON) at 12 μg/kg BW (group D, n = 9), a mixture of ZEN and DON (group M, n = 9) or a placebo [...] Read more.
Immature gilts were administered per os with zearalenone (ZEN) at 40 μg/kg BW (group Z, n = 9), deoxynivalenol (DON) at 12 μg/kg BW (group D, n = 9), a mixture of ZEN and DON (group M, n = 9) or a placebo (group C, n = 9) over a period of six weeks. The pigs were sacrificed after one, three, or six weeks of the treatment (12 pigs per each time-point). Histological investigations revealed an increase in the mucosal thickness and the crypt depth as well as a decrease in the ratio of the villus height to the crypt depth in groups D and M after six weeks of exposure to the mycotoxins. The number of goblet cells in the villus epithelium was elevated in groups Z and M after one week and in group D after three weeks. The administration of ZEN increased the lymphocyte number in the villus epithelium after 1 week and the plasma cell quantity in the lamina propria after one, three, and six weeks of the experiment. DON treatment resulted in an increase in the lymphocyte number in the villus epithelium and the lamina propria after six weeks, and in the plasma cell quantity in the lamina propria after one, three, and six weeks of exposure. In group M, lymphocyte counts in the epithelium and the lamina propria increased significantly after six weeks. Neither mycotoxin induced significant adverse changes in the ultrastructure of the mucosal epithelium and the lamina propria or in the intestinal barrier permeability. Our results indicate that immune cells are the principal target of low doses of ZEN and DON. Full article
(This article belongs to the Special Issue Mycotoxins and Human Diseases 2015)
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Article
Delay of the Onset of Puberty in Female Rats by Prepubertal Exposure to T-2 Toxin
by Rong Yang, Yi-Mei Wang, Li-Shi Zhang, Li Zhang, Zeng-Ming Zhao, Jun Zhao and Shuang-Qing Peng
Toxins 2015, 7(11), 4668-4683; https://doi.org/10.3390/toxins7114668 - 9 Nov 2015
Cited by 18 | Viewed by 6527
Abstract
Growing evidence has revealed the deleterious influence of environmental and food contaminants on puberty onset and development in both animals and children, provoking an increasing health concern. T-2 toxin, a naturally-produced Type A trichothecene mycotoxin which is frequently found in cereal grains and [...] Read more.
Growing evidence has revealed the deleterious influence of environmental and food contaminants on puberty onset and development in both animals and children, provoking an increasing health concern. T-2 toxin, a naturally-produced Type A trichothecene mycotoxin which is frequently found in cereal grains and products intended for human and animal consumption, has been shown to impair the reproduction and development in animals. Nevertheless, whether this trichothecene mycotoxin can disturb the onset of puberty in females remains unclear. To clarify this point, infantile female rats were given a daily intragastric administration of vehicle or 187.5 μg/kg body weight of T-2 toxin for five consecutive days from postnatal day 15 to 19, and the effects on puberty onset were evaluated in the present study. The results revealed that the days of vaginal opening, first dioestrus, and first estrus in regular estrous cycle were delayed following prepubertal exposure to T-2 toxin. The relative weights of reproductive organs uterus, ovaries, and vagina, and the incidence of corpora lutea were all diminished in T-2 toxin-treated rats. Serum levels of gonadotropins luteinizing hormone, follicle-stimulating hormone, and estradiol were also reduced by T-2 toxin treatment. The mRNA expressions of hypothalamic gonadotropin-releasing hormone (GnRH) and pituitary GnRH receptor displayed significant reductions following exposure to T-2 toxin, which were consistent with the changes of serum gonadotropins, delayed reproductive organ development, and delayed vaginal opening. In conclusion, the present study reveals that prepubertal exposure to T-2 toxin delays the onset of puberty in immature female rats, probably by the mechanism of disturbance of hypothalamic-pituitary-gonadal (HPG) axis function. Considering the vulnerability of developmental children to food contaminants and the relative high level of dietary intake of T-2 toxin in children, we think the findings of the present study provide valuable information for the health risk assessment in children. Full article
(This article belongs to the Special Issue Mycotoxins and Human Diseases 2015)
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Article
The Mutation Glu151Asp in the B-Component of the Bacillus cereus Non-Hemolytic Enterotoxin (Nhe) Leads to a Diverging Reactivity in Antibody-Based Detection Systems
by Andrea Didier, Nadja Jeßberger, Victoria Krey, Richard Dietrich, Siegfried Scherer and Erwin Märtlbauer
Toxins 2015, 7(11), 4655-4667; https://doi.org/10.3390/toxins7114655 - 9 Nov 2015
Cited by 6 | Viewed by 5476
Abstract
The ability of Bacillus cereus to cause foodborne toxicoinfections leads to increasing concerns regarding consumer protection. For the diarrhea-associated enterotoxins, the assessment of the non-hemolytic enterotoxin B (NheB) titer determined by a sandwich enzyme immunoassay (EIA) correlates best with in vitro cytotoxicity. In [...] Read more.
The ability of Bacillus cereus to cause foodborne toxicoinfections leads to increasing concerns regarding consumer protection. For the diarrhea-associated enterotoxins, the assessment of the non-hemolytic enterotoxin B (NheB) titer determined by a sandwich enzyme immunoassay (EIA) correlates best with in vitro cytotoxicity. In general, the regulation of enterotoxin expression of B. cereus is a coordinately-regulated process influenced by environmental, and probably also by host factors. As long as these factors are not completely understood, the currently-applied diagnostic procedures are based on indirect approaches to assess the potential virulence of an isolate. To date, sandwich EIA results serve as a surrogate marker to categorize isolates as either potentially low or highly toxic. Here, we report on a single amino acid exchange in the NheB sequence leading to an underestimation of the cytotoxic potential in a limited number of strains. During the screening of a large panel of B. cereus isolates, six showed uncommon features with low sandwich EIA titers despite high cytotoxicity. Sequence analysis revealed the point-mutation Glu151Asp in the potential binding region of the capture antibody. Application of this antibody also results in low titers in an indirect EIA format and shows variable detection intensities in Western-immunoblots. A commercially-available assay based on a lateral flow device detects all strains correctly as NheB producers in a qualitative manner. In conclusion, isolates showing low NheB titers should additionally be assayed in an indirect EIA or for their in vitro cytotoxicity to ensure a correct classification as either low or highly toxic. Full article
(This article belongs to the Collection Rapid Detection of Bacterial Toxins)
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Article
Questionnaire about the Adverse Events and Side Effects Following Botulinum Toxin A Treatment in Patients with Cerebral Palsy
by Izabela Blaszczyk, Nazli Poorsafar Foumani, Christina Ljungberg and Mikael Wiberg
Toxins 2015, 7(11), 4645-4654; https://doi.org/10.3390/toxins7114645 - 6 Nov 2015
Cited by 23 | Viewed by 7850
Abstract
Botulinum toxin A (BoNT-A) injections for treatment of spasticity in patients with cerebral palsy (CP) have been used for about two decades. The treatment is considered safe but a low frequency of adverse events (AE) has been reported. A good method to report [...] Read more.
Botulinum toxin A (BoNT-A) injections for treatment of spasticity in patients with cerebral palsy (CP) have been used for about two decades. The treatment is considered safe but a low frequency of adverse events (AE) has been reported. A good method to report AEs is necessary to verify the safety of the treatment. We decided to use an active surveillance of treatment-induced harm using a questionnaire we created. We studied the incidence of reported AEs and side effects in patients with CP treated with BoNT-A. We investigated the relationship between the incidence of AEs or side effects and gender, age, weight, total dose, dose per body weight, Gross Motor Function Classification System (GMFCS) and number of treated body parts. Seventy-four patients with CP participated in our study. In 54 (51%) of 105 BoNT-A treatments performed in 45 (61%) patients, there were 95 AEs and side effects reported, out of which 50 were generalized and/or focal distant. Severe AEs occurred in three patients (4%), and their BoNT-A treatment was discontinued. Consecutive collection of the AE and side-effect incidence using our questionnaire can increase the safety of BoNT-A treatment in patients with CP. Full article
(This article belongs to the Section Bacterial Toxins)
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Article
Studies on the Bioavailability of Deoxynivalenol (DON) and DON Sulfonate (DONS) 1, 2, and 3 in Pigs Fed with Sodium Sulfite-Treated DON-Contaminated Maize
by Marleen Paulick, Janine Winkler, Susanne Kersten, Dian Schatzmayr, Heidi Elisabeth Schwartz-Zimmermann and Sven Dänicke
Toxins 2015, 7(11), 4622-4644; https://doi.org/10.3390/toxins7114622 - 5 Nov 2015
Cited by 16 | Viewed by 5419
Abstract
Deoxynivalenol (DON) exposure of pigs might cause serious problems when critical dietary toxin concentrations are exceeded. As DON contamination of agricultural crops cannot be completely prevented, detoxification measures are needed. Wet preservation with sodium sulfite resulted in a significant DON reduction of naturally-contaminated [...] Read more.
Deoxynivalenol (DON) exposure of pigs might cause serious problems when critical dietary toxin concentrations are exceeded. As DON contamination of agricultural crops cannot be completely prevented, detoxification measures are needed. Wet preservation with sodium sulfite resulted in a significant DON reduction of naturally-contaminated maize in previous experiments. The preserved material had a characteristic DON sulfonates (DONS) pattern. DONS is known to be less toxic than DON but its stability was shown to depend on pH, which gives rise to the question if a back-conversion to DON occurs in vivo. Therefore, the toxicokinetics and bioavailability of DON and DONS were studied in pigs. After the administration of a single oral or intravenous bolus of DON or DONS, serial blood samples were collected and subsequently analyzed. DONS was not detectable after oral administration of DONS mixtures. The results showed further that the bioavailability of DONS as DON in pigs fed maize preserved wet with sodium sulfite was significantly decreased compared to untreated control maize (DON), indicating that DONS obviously did not convert back to DON to a large extent in vivo. Moreover, the fact that DONS was not detectable in systemic blood requires further investigations regarding their ingestive and/or metabolic fate. Full article
(This article belongs to the Collection Fusarium Toxins – Relevance for Human and Animal Health)
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Article
Cell-to-Cell Propagation of the Bacterial Toxin CNF1 via Extracellular Vesicles: Potential Impact on the Therapeutic Use of the Toxin
by Alessia Fabbri, Sara Cori, Cristiana Zanetti, Marco Guidotti, Massimo Sargiacomo, Stefano Loizzo and Carla Fiorentini
Toxins 2015, 7(11), 4610-4621; https://doi.org/10.3390/toxins7114610 - 5 Nov 2015
Cited by 7 | Viewed by 5073
Abstract
Eukaryotic cells secrete extracellular vesicles (EVs), either constitutively or in a regulated manner, which represent an important mode of intercellular communication. EVs serve as vehicles for transfer between cells of membrane and cytosolic proteins, lipids and RNA. Furthermore, certain bacterial protein toxins, or [...] Read more.
Eukaryotic cells secrete extracellular vesicles (EVs), either constitutively or in a regulated manner, which represent an important mode of intercellular communication. EVs serve as vehicles for transfer between cells of membrane and cytosolic proteins, lipids and RNA. Furthermore, certain bacterial protein toxins, or possibly their derived messages, can be transferred cell to cell via EVs. We have herein demonstrated that eukaryotic EVs represent an additional route of cell-to-cell propagation for the Escherichia coli protein toxin cytotoxic necrotizing factor 1 (CNF1). Our results prove that EVs from CNF1 pre-infected epithelial cells can induce cytoskeleton changes, Rac1 and NF-κB activation comparable to that triggered by CNF1. The observation that the toxin is detectable inside EVs derived from CNF1-intoxicated cells strongly supports the hypothesis that extracellular vesicles can offer to the toxin a novel route to travel from cell to cell. Since anthrax and tetanus toxins have also been reported to engage in the same process, we can hypothesize that EVs represent a common mechanism exploited by bacterial toxins to enhance their pathogenicity. Full article
(This article belongs to the Section Bacterial Toxins)
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Article
Mycotoxigenic Fungi and Natural Co-Occurrence of Mycotoxins in Rainbow Trout (Oncorhynchus mykiss) Feeds
by Mariana Greco, Alejandro Pardo and Graciela Pose
Toxins 2015, 7(11), 4595-4609; https://doi.org/10.3390/toxins7114595 - 5 Nov 2015
Cited by 40 | Viewed by 6605
Abstract
Samples of rainbow trout feed were analyzed with the aim to determine the mycobiota composition and the co-occurrence of mycotoxins. A total of 28 samples of finished rainbow trout feed from hatcheries in the provinces of Río Negro and Neuquén, Argentina, were studied. [...] Read more.
Samples of rainbow trout feed were analyzed with the aim to determine the mycobiota composition and the co-occurrence of mycotoxins. A total of 28 samples of finished rainbow trout feed from hatcheries in the provinces of Río Negro and Neuquén, Argentina, were studied. Fungal counts were obtained on three culture media in the ranges of <10 to 4.2 × 104 CFU/g on Dichloran Rose Bengal Chloramphenicol Agar (DRBC), <10 to 5.1 × 104 CFU/g on Dichloran Chloramphenicol Peptone Agar (DCPA) and <10 to 3.6 × 104 CFU/g on Dichloran 18% Glycerol Agar (DG18). The most frequent mycotoxigenic fungi were Eurotium (frequency (Fr) 25.0%), followed by Penicillium (Fr 21.4%) and Aspergillus (Fr 3.6%). The most prevalent mycotoxigenic species were E. repens (Fr 21.4%) and E. rubrum (Fr 14.3%). All samples were contaminated with mycotoxins: 64% samples were contaminated with T-2 toxin (median 70.08 ppb), 50% samples with zearalenone (median 87.97 ppb) and aflatoxins (median 2.82 ppb), 25% with ochratoxin A (median 5.26 ppb) and 3.57% samples with deoxynivalenol (median 230 ppb). Eight samples had a fumonisins contamination level below the limit of detection. Co-occurrence of six mycotoxins was determined in 7% of the samples. Full article
(This article belongs to the Section Mycotoxins)
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3195 KiB  
Article
Variation in Type A Trichothecene Production and Trichothecene Biosynthetic Genes in Fusarium goolgardi from Natural Ecosystems of Australia
by Liliana O. Rocha, Matthew H. Laurence, Robert H. Proctor, Susan P. McCormick, Brett A. Summerell and Edward C. Y. Liew
Toxins 2015, 7(11), 4577-4594; https://doi.org/10.3390/toxins7114577 - 5 Nov 2015
Cited by 18 | Viewed by 5365
Abstract
Fusarium goolgardi, isolated from the grass tree Xanthorrhoea glauca in natural ecosystems of Australia, is closely related to fusaria that produce a subgroup of trichothecene (type A) mycotoxins that lack a carbonyl group at carbon atom 8 (C-8). Mass spectrometric analysis revealed that [...] Read more.
Fusarium goolgardi, isolated from the grass tree Xanthorrhoea glauca in natural ecosystems of Australia, is closely related to fusaria that produce a subgroup of trichothecene (type A) mycotoxins that lack a carbonyl group at carbon atom 8 (C-8). Mass spectrometric analysis revealed that F. goolgardi isolates produce type A trichothecenes, but exhibited one of two chemotypes. Some isolates (50%) produced multiple type A trichothecenes, including 4,15-diacetoxyscirpenol (DAS), neosolaniol (NEO), 8-acetylneosolaniol (Ac-NEO) and T-2 toxin (DAS-NEO-T2 chemotype). Other isolates (50%) produced only DAS (DAS chemotype). In the phylogenies inferred from DNA sequences of genes encoding the RNA polymerase II largest (RPB1) and second largest (RPB2) subunits as well as the trichothecene biosynthetic genes (TRI), F. goolgardi isolates were resolved as a monophyletic clade, distinct from other type A trichothecene-producing species. However, the relationships of F. goolgardi to the other species varied depending on whether phylogenies were inferred from RPB1 and RPB2, the 12-gene TRI cluster, the two-gene TRI1-TRI16 locus, or the single-gene TRI101 locus. Phylogenies based on different TRI loci resolved isolates with different chemotypes into distinct clades, even though only the TRI1-TRI16 locus is responsible for structural variation at C-8. Sequence analysis indicated that TRI1 and TRI16 are functional in F. goolgardi isolates with the DAS-NEO-T2 chemotype, but non-functional in isolates with DAS chemotype due to the presence of premature stop codons caused by a point mutation. Full article
(This article belongs to the Section Mycotoxins)
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Article
A Rapid and Sensitive Method to Measure the Functional Activity of Shiga Toxins in Human Serum
by Valentina Arfilli, Domenica Carnicelli, Gianluigi Ardissino, Erminio Torresani, Gaia Scavia and Maurizio Brigotti
Toxins 2015, 7(11), 4564-4576; https://doi.org/10.3390/toxins7114564 - 4 Nov 2015
Cited by 12 | Viewed by 5343
Abstract
Shiga toxins (Stx) have a definite role in the development of hemolytic uremic syndrome in children with hemorrhagic colitis caused by pathogenic Stx-producing Escherichia coli (STEC) strains. The dramatic effects of these toxins on the microvasculature of different organs, particularly of the kidney, [...] Read more.
Shiga toxins (Stx) have a definite role in the development of hemolytic uremic syndrome in children with hemorrhagic colitis caused by pathogenic Stx-producing Escherichia coli (STEC) strains. The dramatic effects of these toxins on the microvasculature of different organs, particularly of the kidney, are well known, whereas there is no consensus on the mechanism by which Stx reach the endothelia of target organs and/or indirectly injure these body sites. We hereby describe a quick (4 h), radioactive, Raji cell-based method designed for the detection of Stx in human sera. The assay monitors the translation impairment induced by these powerful inhibitors of protein synthesis, which are identified properly by neutralizing their activity with specific monoclonal antibodies. By this method, we detected for the first time the functional activity of Stx in sera of STEC-infected patients during hemorrhagic colitis. Recent research has pointed to a dynamic process of Stx-induced renal intoxication in which concurrent and interactive steps are involved. Our rapid and specific method could be useful for studying the kinetics of Stx during the natural course of STEC infection and the interplay between Stx activity in serum and Stx presence in different blood fractions (neutrophils, monocytes, platelets, leukocyte-platelet aggregates, microvesicles, lipoproteins). Full article
(This article belongs to the Collection Rapid Detection of Bacterial Toxins)
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Review
Current Status and Future Directions of Botulinum Neurotoxins for Targeting Pain Processing
by Sabine Pellett, Tony L. Yaksh and Roshni Ramachandran
Toxins 2015, 7(11), 4519-4563; https://doi.org/10.3390/toxins7114519 - 4 Nov 2015
Cited by 55 | Viewed by 10774
Abstract
Current evidence suggests that botulinum neurotoxins (BoNTs) A1 and B1, given locally into peripheral tissues such as skin, muscles, and joints, alter nociceptive processing otherwise initiated by inflammation or nerve injury in animal models and humans. Recent data indicate that such locally delivered [...] Read more.
Current evidence suggests that botulinum neurotoxins (BoNTs) A1 and B1, given locally into peripheral tissues such as skin, muscles, and joints, alter nociceptive processing otherwise initiated by inflammation or nerve injury in animal models and humans. Recent data indicate that such locally delivered BoNTs exert not only local action on sensory afferent terminals but undergo transport to central afferent cell bodies (dorsal root ganglia) and spinal dorsal horn terminals, where they cleave SNAREs and block transmitter release. Increasing evidence supports the possibility of a trans-synaptic movement to alter postsynaptic function in neuronal and possibly non-neuronal (glial) cells. The vast majority of these studies have been conducted on BoNT/A1 and BoNT/B1, the only two pharmaceutically developed variants. However, now over 40 different subtypes of botulinum neurotoxins (BoNTs) have been identified. By combining our existing and rapidly growing understanding of BoNT/A1 and /B1 in altering nociceptive processing with explorations of the specific characteristics of the various toxins from this family, we may be able to discover or design novel, effective, and long-lasting pain therapeutics. This review will focus on our current understanding of the molecular mechanisms whereby BoNTs alter pain processing, and future directions in the development of these agents as pain therapeutics. Full article
(This article belongs to the Collection Botulinum Toxins on Human Pain)
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645 KiB  
Article
Cytotoxic Indole Alkaloids against Human Leukemia Cell Lines from the Toxic Plant Peganum harmala
by Chunhua Wang, Zhenxue Zhang, Yihai Wang and Xiangjiu He
Toxins 2015, 7(11), 4507-4518; https://doi.org/10.3390/toxins7114507 - 3 Nov 2015
Cited by 38 | Viewed by 5998
Abstract
Bioactivity-guided fractionation was used to determine the cytotoxic alkaloids from the toxic plant Peganum harmala. Two novel indole alkaloids, together with ten known ones, were isolated and identified. The novel alkaloids were elucidated to be 2-(indol-3-yl)ethyl-α-L-rhamnopyranosyl-(1 → 6)-β-D-glucopyranoside (2) and 3-hydroxy-3-(N-acetyl-2-aminoethyl)-6-methoxyindol-2-one (3). The [...] Read more.
Bioactivity-guided fractionation was used to determine the cytotoxic alkaloids from the toxic plant Peganum harmala. Two novel indole alkaloids, together with ten known ones, were isolated and identified. The novel alkaloids were elucidated to be 2-(indol-3-yl)ethyl-α-L-rhamnopyranosyl-(1 → 6)-β-D-glucopyranoside (2) and 3-hydroxy-3-(N-acetyl-2-aminoethyl)-6-methoxyindol-2-one (3). The cytotoxicity against human leukemia cells was assayed for the alkaloids and some of them showed potent activity. Harmalacidine (compound 8, HMC) exhibited the highest cytotoxicity against U-937 cells with IC50 value of 3.1 ± 0.2 μmol/L. The cytotoxic mechanism of HMC was targeting the mitochondrial and protein tyrosine kinase signaling pathways (PTKs-Ras/Raf/ERK). The results strongly demonstrated that the alkaloids from Peganum harmala could be a promising candidate for the therapy of leukemia. Full article
(This article belongs to the Collection Toxicity of Natural Alkaloids)
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304 KiB  
Editorial
Introduction to the Toxins Special Issue on Plant Toxins
by Nilgun E. Tumer
Toxins 2015, 7(11), 4503-4506; https://doi.org/10.3390/toxins7114503 - 2 Nov 2015
Cited by 2 | Viewed by 4746
Abstract
Plants express a variety of toxic proteins which are thought to have a role in defense against pathogens and insects. [...] Full article
(This article belongs to the Special Issue Plant Toxins)
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Review
Effects of Mycotoxins on Mucosal Microbial Infection and Related Pathogenesis
by Seong-Hwan Park, Dongwook Kim, Juil Kim and Yuseok Moon
Toxins 2015, 7(11), 4484-4502; https://doi.org/10.3390/toxins7114484 - 30 Oct 2015
Cited by 20 | Viewed by 6494
Abstract
Mycotoxins are fungal secondary metabolites detected in many agricultural commodities and water-damaged indoor environments. Susceptibility to mucosal infectious diseases is closely associated with immune dysfunction caused by mycotoxin exposure in humans and other animals. Many mycotoxins suppress immune function by decreasing the proliferation [...] Read more.
Mycotoxins are fungal secondary metabolites detected in many agricultural commodities and water-damaged indoor environments. Susceptibility to mucosal infectious diseases is closely associated with immune dysfunction caused by mycotoxin exposure in humans and other animals. Many mycotoxins suppress immune function by decreasing the proliferation of activated lymphocytes, impairing phagocytic function of macrophages, and suppressing cytokine production, but some induce hypersensitive responses in different dose regimes. The present review describes various mycotoxin responses to infectious pathogens that trigger mucosa-associated diseases in the gastrointestinal and respiratory tracts of humans and other animals. In particular, it focuses on the effects of mycotoxin exposure on invasion, pathogen clearance, the production of cytokines and immunoglobulins, and the prognostic implications of interactions between infectious pathogens and mycotoxin exposure. Full article
(This article belongs to the Special Issue Mycotoxins and Human Diseases 2015)
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Article
Honeybee Venom Proteome Profile of Queens and Winter Bees as Determined by a Mass Spectrometric Approach
by Ellen L. Danneels, Matthias Van Vaerenbergh, Griet Debyser, Bart Devreese and Dirk C. De Graaf
Toxins 2015, 7(11), 4468-4483; https://doi.org/10.3390/toxins7114468 - 30 Oct 2015
Cited by 57 | Viewed by 8923
Abstract
Venoms of invertebrates contain an enormous diversity of proteins, peptides, and other classes of substances. Insect venoms are characterized by a large interspecific variation resulting in extended lists of venom compounds. The venom composition of several hymenopterans also shows different intraspecific variation. For [...] Read more.
Venoms of invertebrates contain an enormous diversity of proteins, peptides, and other classes of substances. Insect venoms are characterized by a large interspecific variation resulting in extended lists of venom compounds. The venom composition of several hymenopterans also shows different intraspecific variation. For instance, venom from different honeybee castes, more specifically queens and workers, shows quantitative and qualitative variation, while the environment, like seasonal changes, also proves to be an important factor. The present study aimed at an in-depth analysis of the intraspecific variation in the honeybee venom proteome. In summer workers, the recent list of venom proteins resulted from merging combinatorial peptide ligand library sample pretreatment and targeted tandem mass spectrometry realized with a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS/MS). Now, the same technique was used to determine the venom proteome of queens and winter bees, enabling us to compare it with that of summer bees. In total, 34 putative venom toxins were found, of which two were never described in honeybee venoms before. Venom from winter workers did not contain toxins that were not present in queens or summer workers, while winter worker venom lacked the allergen Api m 12, also known as vitellogenin. Venom from queen bees, on the other hand, was lacking six of the 34 venom toxins compared to worker bees, while it contained two new venom toxins, in particularly serine proteinase stubble and antithrombin-III. Although people are hardly stung by honeybees during winter or by queen bees, these newly identified toxins should be taken into account in the characterization of a putative allergic response against Apis mellifera stings. Full article
(This article belongs to the Special Issue Arthropod Venoms)
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3837 KiB  
Article
The Saccharomyces boulardii CNCM I-745 Strain Shows Protective Effects against the B. anthracis LT Toxin
by Rodolphe Pontier-Bres, Patrick Rampal, Jean-François Peyron, Patrick Munro, Emmanuel Lemichez and Dorota Czerucka
Toxins 2015, 7(11), 4455-4467; https://doi.org/10.3390/toxins7114455 - 30 Oct 2015
Cited by 8 | Viewed by 8106
Abstract
The probiotic yeast Saccharomyces boulardii (S. boulardii) has been prescribed for the prophylaxis and treatment of several infectious diarrheal diseases. Gastrointestinal anthrax causes fatal systemic disease. In the present study, we investigated the protective effects conferred by Saccharomyces boulardii CNCM I-745 [...] Read more.
The probiotic yeast Saccharomyces boulardii (S. boulardii) has been prescribed for the prophylaxis and treatment of several infectious diarrheal diseases. Gastrointestinal anthrax causes fatal systemic disease. In the present study, we investigated the protective effects conferred by Saccharomyces boulardii CNCM I-745 strain on polarized T84 columnar epithelial cells intoxicated by the lethal toxin (LT) of Bacillus anthracis. Exposure of polarized T84 cells to LT affected cell monolayer integrity, modified the morphology of tight junctions and induced the formation of actin stress fibers. Overnight treatment of cells with S. boulardii before incubation with LT maintained the integrity of the monolayers, prevented morphological modification of tight junctions, restricted the effects of LT on actin remodeling and delayed LT-induced MEK-2 cleavage. Mechanistically, we demonstrated that in the presence of S. boulardii, the medium is depleted of both LF and PA sub-units of LT and the appearance of a cleaved form of PA. Our study highlights the potential of the S. boulardii CNCM I-745 strain as a prophylactic agent against the gastrointestinal form of anthrax. Full article
(This article belongs to the Collection Anthrax Toxins)
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645 KiB  
Article
Acupoint Injection of Onabotulinumtoxin A for Migraines
by Min Hou, Jun-Fan Xie, Xiang-Pan Kong, Yi Zhang, Yu-Feng Shao, Can Wang, Wen-Ting Ren, Guang-Fu Cui, Le Xin and Yi-Ping Hou
Toxins 2015, 7(11), 4442-4454; https://doi.org/10.3390/toxins7114442 - 30 Oct 2015
Cited by 18 | Viewed by 9339
Abstract
Onabotulinumtoxin A (BoNTA) has been reported to be effective in the therapy for migraines. Acupuncture has been used worldwide for the treatment of migraine attacks. Injection of a small amount of drug at acupuncture points is an innovation as compared to traditional acupuncture. [...] Read more.
Onabotulinumtoxin A (BoNTA) has been reported to be effective in the therapy for migraines. Acupuncture has been used worldwide for the treatment of migraine attacks. Injection of a small amount of drug at acupuncture points is an innovation as compared to traditional acupuncture. The purpose of this study was to evaluate and compare the effectiveness of fixed (muscle)-site and acupoint-site injections of BoNTA for migraine therapy in a randomized, double-blinded, placebo-controlled clinical trial extending over four months. Subjects with both episodic and chronic migraines respectively received a placebo (n = 19) or BoNTA (2.5 U each site, 25 U per subject) injection at fixed-sites (n = 41) including occipitofrontalis, corrugator supercilii, temporalis and trapeziue, or at acupoint-sites (n = 42) including Yintang (EX-HN3), Taiyang (EX-HN5), Baihui (GV20), Shuaigu (GB8), Fengchi (GB20) and Tianzhu (BL10). The variations between baseline and BoNTA post-injection for four months were calculated monthly as outcome measures. BoNTA injections at fixed-sites and acupoint-sites significantly reduced the migraine attack frequency, intensity, duration and associated symptoms for four months compared with placebo (p < 0.01). The efficacy of BoNTA for migraines in the acupoint-site group (93% improvement) was more significant than that in the fixed-site group (85% improvement) (p < 0.01). BoNTA administration for migraines is effective, and at acupoint-sites shows more efficacy than at fixed-sites. Further blinded studies are necessary to establish the efficacy of a low dose toxin (25 U) introduced with this methodology in chronic and episodic migraines. Full article
(This article belongs to the Collection Botulinum Toxins on Human Pain)
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303 KiB  
Editorial
Editorial on the Special Issue “Harmful Algal Blooms (HABs) and Public Health: Progress and Current Challenges”
by Lesley V. D'Anglada
Toxins 2015, 7(11), 4437-4441; https://doi.org/10.3390/toxins7114437 - 30 Oct 2015
Cited by 11 | Viewed by 4731
Abstract
Harmful Algal Blooms (HABs) affect the quality of fresh and marine waters and adversely affect both animals and humans. [...] Full article
(This article belongs to the Special Issue Harmful Algal Blooms (HABs) and Public Health: Progress and Current Challenges)
1140 KiB  
Review
Polyketides, Toxins and Pigments in Penicillium marneffei
by Emily W. T. Tam, Chi-Ching Tsang, Susanna K. P. Lau and Patrick C. Y. Woo
Toxins 2015, 7(11), 4421-4436; https://doi.org/10.3390/toxins7114421 - 30 Oct 2015
Cited by 31 | Viewed by 8620
Abstract
Penicillium marneffei (synonym: Talaromyces marneffei) is the most important pathogenic thermally dimorphic fungus in China and Southeastern Asia. The HIV/AIDS pandemic, particularly in China and other Southeast Asian countries, has led to the emergence of P. marneffei infection as an important AIDS-defining [...] Read more.
Penicillium marneffei (synonym: Talaromyces marneffei) is the most important pathogenic thermally dimorphic fungus in China and Southeastern Asia. The HIV/AIDS pandemic, particularly in China and other Southeast Asian countries, has led to the emergence of P. marneffei infection as an important AIDS-defining condition. Recently, we published the genome sequence of P. marneffei. In the P. marneffei genome, 23 polyketide synthase genes and two polyketide synthase-non-ribosomal peptide synthase hybrid genes were identified. This number is much higher than those of Coccidioides immitis and Histoplasma capsulatum, important pathogenic thermally dimorphic fungi in the Western world. Phylogenetically, these polyketide synthase genes were distributed evenly with their counterparts found in Aspergillus species and other fungi, suggesting that polyketide synthases in P. marneffei did not diverge from lineage-specific gene duplication through a recent expansion. Gene knockdown experiments and ultra-high performance liquid chromatography-photodiode array detector/electrospray ionization-quadruple time of flight-mass spectrometry analysis confirmed that at least four of the polyketide synthase genes were involved in the biosynthesis of various pigments in P. marneffei, including melanin, mitorubrinic acid, mitorubrinol, monascorubrin, rubropunctatin, citrinin and ankaflavin, some of which were mycotoxins and virulence factors of the fungus. Full article
(This article belongs to the Collection Evolutionary/Phylogenetic Studies of Mycotoxin Biosynthetic Pathways)
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Article
Nodularia spumigena Peptides—Accumulation and Effect on Aquatic Invertebrates
by Hanna Mazur-Marzec, Katarzyna Sutryk, Agnieszka Hebel, Natalia Hohlfeld, Anna Pietrasik and Agata Błaszczyk
Toxins 2015, 7(11), 4404-4420; https://doi.org/10.3390/toxins7114404 - 30 Oct 2015
Cited by 15 | Viewed by 5388
Abstract
Thus far, the negative effects of Nodularia spumigena blooms on aquatic organisms have been mainly attributed to the production of the hepatotoxic nodularin (NOD). In the current work, the accumulation of other N. spumigena metabolites in blue mussels and crustaceans, and their effect [...] Read more.
Thus far, the negative effects of Nodularia spumigena blooms on aquatic organisms have been mainly attributed to the production of the hepatotoxic nodularin (NOD). In the current work, the accumulation of other N. spumigena metabolites in blue mussels and crustaceans, and their effect on Thamnocephalus platyurus and Artemia franciscana, were examined. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses provided evidence that both blue mussels collected after a cyanobacterial bloom in the Baltic Sea and the crustaceans exposed under laboratory conditions to N. spumigena extract accumulated the cyclic anabaenopeptins (APs). In the crustaceans, the linear peptides, spumigins (SPUs) and aeruginosins (AERs), were additionally detected. Exposure of T. platyurus and A. franciscana to N. spumigena extract confirmed the negative effect of nodularin on the organisms. However, high numbers of dead crustaceans were also recorded in the nodularin-free fraction, which contained protease inhibitors classified to spumigins and aeruginosins. These findings indicate that cyanobacterial toxicity to aquatic organisms is a complex phenomenon and the induced effects can be attributed to diverse metabolites, not only to the known hepatotoxins. Full article
(This article belongs to the Special Issue Bioactivity and Toxicity in Marine Cyanobacteria)
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Article
Indolic Uremic Solutes Enhance Procoagulant Activity of Red Blood Cells through Phosphatidylserine Exposure and Microparticle Release
by Chunyan Gao, Shuting Ji, Weijun Dong, Yushan Qi, Wen Song, Debin Cui and Jialan Shi
Toxins 2015, 7(11), 4390-4403; https://doi.org/10.3390/toxins7114390 - 28 Oct 2015
Cited by 38 | Viewed by 5875
Abstract
Increased accumulation of indolic uremic solutes in the blood of uremic patients contributes to the risk of thrombotic events. Red blood cells (RBCs), the most abundant blood cells in circulation, may be a privileged target of these solutes. However, the effect of uremic [...] Read more.
Increased accumulation of indolic uremic solutes in the blood of uremic patients contributes to the risk of thrombotic events. Red blood cells (RBCs), the most abundant blood cells in circulation, may be a privileged target of these solutes. However, the effect of uremic solutes indoxyl sulfate (IS) and indole-3-acetic acid (IAA) on procoagulant activity (PCA) of erythrocyte is unclear. Here, RBCs from healthy adults were treated with IS and IAA (mean and maximal concentrations reported in uremic patients). Phosphatidylserine (PS) exposure of RBCs and their microparticles (MPs) release were labeled with Alexa Fluor 488-lactadherin and detected by flow cytometer. Cytosolic Ca2+ ([Ca2+]) with Fluo 3/AM was analyzed by flow cytometer. PCA was assessed by clotting time and purified coagulation complex assays. We found that PS exposure, MPs generation, and consequent PCA of RBCs at mean concentrations of IS and IAA enhanced and peaked in maximal uremic concentrations. Moreover, 128 nM lactadherin, a PS inhibitor, inhibited over 90% PCA of RBCs and RMPs. Eryptosis or damage, by indolic uremic solutes was due to, at least partially, the increase of cytosolic [Ca2+]. Our results suggest that RBC eryptosis in uremic solutes IS and IAA plays an important role in thrombus formation through releasing RMPs and exposing PS. Lactadherin acts as an efficient anticoagulant in this process. Full article
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