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Toxins
Volume 10
Issue 7
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Toxins, Volume 10, Issue 7 (July 2018) – 52 articles

Cover Story (view full-size image): The Mexican Lance-headed Rattlesnake (Crotalus polystictus) occupies native and modified grasslands in central México and feeds primarily on rodents. Ontogeny of the venom proteome follows a typical type I pattern, with neonates showing very low venom SVMP activity that increases dramatically as snakes age, while PLA2 shows the opposite pattern. Increases in SVMP activity with age are due to increases in PIII and PI metalloproteinases in adult venoms, as demonstrated via MALDI-TOF-MS/MS. Venom ontogeny appears to be driven by changes in prey size rather than type as was observed in other species such as Crotalus oreganus helleri and C. o. oreganus. (Photo by Estrella Mociño-Deloya and Kirk Setser) View this paper.
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14 pages, 2624 KiB  
Article
Determination of the Role of Microcystis aeruginosa in Toxin Generation Based on Phosphoproteomic Profiles
by Jiangqi Qu, Liping Shen, Meng Zhao, Wentong Li, Chengxia Jia, Hua Zhu and Qingjing Zhang
Toxins 2018, 10(7), 304; https://doi.org/10.3390/toxins10070304 - 23 Jul 2018
Cited by 23 | Viewed by 4564
Abstract
Microcystis aeruginosa is the most common species responsible for toxic cyanobacterial blooms and is considered a significant contributor to the production of cyanotoxins, particularly the potent liver toxins called microcystins. Numerous studies investigating Microcystis spp. blooms have revealed their deleterious effects in freshwater [...] Read more.
Microcystis aeruginosa is the most common species responsible for toxic cyanobacterial blooms and is considered a significant contributor to the production of cyanotoxins, particularly the potent liver toxins called microcystins. Numerous studies investigating Microcystis spp. blooms have revealed their deleterious effects in freshwater environments. However, the available knowledge regarding the global phosphoproteomics of M. aeruginosa and their regulatory roles in toxin generation is limited. In this study, we conducted comparative phosphoproteomic profiling of non-toxic and toxin-producing strains of M. aeruginosa. We identified 59 phosphorylation sites in 37 proteins in a non-toxic strain and 26 phosphorylation sites in 18 proteins in a toxin-producing strain. The analysis of protein phosphorylation abundances and functions in redox homeostasis, energy metabolism, light absorption and photosynthesis showed marked differences between the non-toxic and toxin-producing strains of M. aeruginosa, indicating that these processes are strongly related to toxin generation. Moreover, the protein-protein interaction results indicated that BJ0JVG8 can directly interact with the PemK-like toxin protein B0JQN8. Thus, the phosphorylation of B0JQN8 appears to be associated with the regulatory roles of toxins in physiological activity. Full article
(This article belongs to the Special Issue Harmful Algal Bloom Dynamics)
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25 pages, 1039 KiB  
Review
The Impact of Uremic Toxins on Cerebrovascular and Cognitive Disorders
by Maryam Assem, Mathilde Lando, Maria Grissi, Saïd Kamel, Ziad A. Massy, Jean-Marc Chillon and Lucie Hénaut
Toxins 2018, 10(7), 303; https://doi.org/10.3390/toxins10070303 - 22 Jul 2018
Cited by 63 | Viewed by 9830
Abstract
Individuals at all stages of chronic kidney disease (CKD) have a higher risk of developing cognitive disorders and dementia. Stroke is also highly prevalent in this population and is associated with a higher risk of neurological deterioration, in-hospital mortality, and poor functional outcomes. [...] Read more.
Individuals at all stages of chronic kidney disease (CKD) have a higher risk of developing cognitive disorders and dementia. Stroke is also highly prevalent in this population and is associated with a higher risk of neurological deterioration, in-hospital mortality, and poor functional outcomes. Evidence from in vitro studies and in vivo animal experiments suggests that accumulation of uremic toxins may contribute to the pathogenesis of stroke and amplify vascular damage, leading to cognitive disorders and dementia. This review summarizes current evidence on the mechanisms by which uremic toxins may favour the occurrence of cerebrovascular diseases and neurological complications in CKD. Full article
(This article belongs to the Special Issue Uremia and Cardiovascular Disease)
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22 pages, 2847 KiB  
Review
Bioengineering of Bordetella pertussis Adenylate Cyclase Toxin for Antigen-Delivery and Immunotherapy
by Alexandre Chenal and Daniel Ladant
Toxins 2018, 10(7), 302; https://doi.org/10.3390/toxins10070302 - 20 Jul 2018
Cited by 19 | Viewed by 7852
Abstract
The adenylate cyclase toxin (CyaA) is one of the major virulence factors of Bordetella pertussis, the causative agent of whooping cough. CyaA is able to invade eukaryotic cells where, upon activation by endogenous calmodulin, it synthesizes massive amounts of cAMP that alters [...] Read more.
The adenylate cyclase toxin (CyaA) is one of the major virulence factors of Bordetella pertussis, the causative agent of whooping cough. CyaA is able to invade eukaryotic cells where, upon activation by endogenous calmodulin, it synthesizes massive amounts of cAMP that alters cellular physiology. The CyaA toxin is a 1706 residues-long bifunctional protein: the catalytic domain is located in the 400 amino-proximal residues, whereas the carboxy-terminal 1306 residues are implicated in toxin binding to the cellular receptor, the αMβ2 (CD11b/CD18) integrin, and subsequently in the translocation of the catalytic domain across the cytoplasmic membrane of the target cells. Indeed, this protein is endowed with the unique capability of delivering its N-terminal catalytic domain directly across the plasma membrane of eukaryotic target cells. These properties have been exploited to engineer the CyaA toxin as a potent non-replicating vector able to deliver antigens into antigen presenting cells and elicit specific cell-mediated immune responses. Antigens of interest can be inserted into the CyaA protein to yield recombinant molecules that are targeted in vivo to dendritic cells, where the antigens are processed and presented by the major class I and class II histocompatibility complexes (MHC-I and II). CyaA turned out to be a remarkably effective and versatile vaccine vector capable of inducing all the components of the immune response (T-CD4, T-CD8, and antibody). In this chapter, we summarize the basic knowledge on the adenylate cyclase toxin and then describe the application of CyaA in vaccinology, including some recent results of clinical trials of immunotherapy using a recombinant CyaA vaccine. Full article
(This article belongs to the Special Issue Adenylate Cyclase (CyaA) Toxin)
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16 pages, 4024 KiB  
Article
The PHD Transcription Factor Rum1 Regulates Morphogenesis and Aflatoxin Biosynthesis in Aspergillus flavus
by Yule Hu, Guang Yang, Danping Zhang, Yaju Liu, Yu Li, Guanglan Lin, Zhiqiang Guo, Shihua Wang and Zhenhong Zhuang
Toxins 2018, 10(7), 301; https://doi.org/10.3390/toxins10070301 - 20 Jul 2018
Cited by 32 | Viewed by 4290
Abstract
Aspergillus flavus produces mycotoxins especially aflatoxin B1 and infects crops worldwide. As a PHD transcription factor, there is no report on the role of Rum1 in the virulence of Aspergillus spp. yet. This study explored the biological function of Rum1 in A. [...] Read more.
Aspergillus flavus produces mycotoxins especially aflatoxin B1 and infects crops worldwide. As a PHD transcription factor, there is no report on the role of Rum1 in the virulence of Aspergillus spp. yet. This study explored the biological function of Rum1 in A. flavus through the construction of rum1 deletion mutants and rum1 complementation strains with the method of homologous recombination. It was found, in the study, that Rum1 negatively regulates conidiation through abaA and brlA, positively regulates sclerotia formation through nsdC, nsdD, and sclR, triggers aflatoxin biological synthesis, and enhances the activity of amylase. Our findings suggested that Rum1 plays a major role in the growth of mycelia, conidia, and sclerotia production along with aflatoxin biosynthesis in A. flavus. Full article
(This article belongs to the Collection Aflatoxins)
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21 pages, 1725 KiB  
Review
Impact of Altered Intestinal Microbiota on Chronic Kidney Disease Progression
by Esmeralda Castillo-Rodriguez, Raul Fernandez-Prado, Raquel Esteras, Maria Vanessa Perez-Gomez, Carolina Gracia-Iguacel, Beatriz Fernandez-Fernandez, Mehmet Kanbay, Alberto Tejedor, Alberto Lazaro, Marta Ruiz-Ortega, Emilio Gonzalez-Parra, Ana B. Sanz, Alberto Ortiz and Maria Dolores Sanchez-Niño
Toxins 2018, 10(7), 300; https://doi.org/10.3390/toxins10070300 - 19 Jul 2018
Cited by 104 | Viewed by 9267
Abstract
In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of CKD progression. Some uremic toxins result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves, such as trimethylamine N-Oxide (TMAO), p-cresyl [...] Read more.
In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of CKD progression. Some uremic toxins result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves, such as trimethylamine N-Oxide (TMAO), p-cresyl sulphate, indoxyl sulphate and indole-3 acetic acid. Increased intake of some nutrients may modify the gut microbiota, increasing the number of bacteria that process them to yield uremic toxins. Circulating levels of nutrient-derived uremic toxins are associated to increased risk of CKD progression. This offers the opportunity for therapeutic intervention by either modifying the diet, modifying the microbiota, decreasing uremic toxin production by microbiota, increasing toxin excretion or targeting specific uremic toxins. We now review the link between nutrients, microbiota and uremic toxin with CKD progression. Specific focus will be placed on the generation specific uremic toxins with nephrotoxic potential, the decreased availability of bacteria-derived metabolites with nephroprotective potential, such as vitamin K and butyrate and the cellular and molecular mechanisms linking these toxins and protective factors to kidney diseases. This information provides a conceptual framework that allows the development of novel therapeutic approaches. Full article
(This article belongs to the Special Issue The Intestine and Uremia)
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10 pages, 684 KiB  
Article
Botulinum Toxin for the Treatment of Hand Tremor
by Nicki Niemann and Joseph Jankovic
Toxins 2018, 10(7), 299; https://doi.org/10.3390/toxins10070299 - 19 Jul 2018
Cited by 45 | Viewed by 7463
Abstract
The aim of this study is to review our longitudinal experience with onabotulinumtoxinA (onaBoNT-A) injections for medically refractory hand tremor. We performed a retrospective review of our database of patients treated with onaBoNT-A for hand tremor evaluated between 2010 and 2018 in at [...] Read more.
The aim of this study is to review our longitudinal experience with onabotulinumtoxinA (onaBoNT-A) injections for medically refractory hand tremor. We performed a retrospective review of our database of patients treated with onaBoNT-A for hand tremor evaluated between 2010 and 2018 in at least 2 sessions with follow-up. The majority were injected into the forearm flexors (FF), although treatment was individualized. During the specified period, 91 patients (53 essential tremor, 31 dystonic tremor, 6 Parkinson’s disease tremor, and 1 cerebellar outflow tremor) met our inclusion criteria. The mean age (SD) was 64.8 years (12.8), and mean duration of follow-up was 29.6 months (25.1) with mean of 7.7 (6.3) treatment visits. FF were injected in 89 (97.8%) patients, exclusively in 74 (81.3%), and 15 (16.5%) were injected in FF and other muscles. EMG guidance was used in 5 patients (5.5%). On a 0–4 “peak effect” rating scale (0 = no effect, 4 = marked improvement in severity and function), 80.2% and 85.7% of patients reported moderate or marked improvement (score 3 or 4) at their first and last follow-up visit, respectively. There was no statistically significant difference in the outcomes between first and last visit: average “peak effect” rating score (3.2 versus 3.4), “global” rating score (3.0 versus 3.2), latency of response (4.5 versus 3.8 days), and total duration of response (12.7 versus 12.8 weeks), except onaBoNT-A dose (65.0 versus 78.6 U/limb, p = 0.002). Of 1095 limb injections, there were 134 (12.2%) non-disabling and transient (mean 36 days) adverse events (132 limb weakness, 2 pain). OnaBoNT-A injections are safe and effective in the treatment of hand tremor. Full article
(This article belongs to the Special Issue Botulinum Neurotoxins and Nervous System: Future Challenges for Novel Indications)
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11 pages, 12457 KiB  
Review
Intestinal Barrier Function in Chronic Kidney Disease
by Björn Meijers, Ricard Farré, Sander Dejongh, Maria Vicario and Pieter Evenepoel
Toxins 2018, 10(7), 298; https://doi.org/10.3390/toxins10070298 - 19 Jul 2018
Cited by 88 | Viewed by 9069
Abstract
The kidneys are key contributors to body homeostasis, by virtue of controlled excretion of excessive fluid, electrolytes, and toxic waste products. The syndrome of uremia equals the altered physiology due to irreversible loss of kidney function that is left uncorrected for, despite therapeutic [...] Read more.
The kidneys are key contributors to body homeostasis, by virtue of controlled excretion of excessive fluid, electrolytes, and toxic waste products. The syndrome of uremia equals the altered physiology due to irreversible loss of kidney function that is left uncorrected for, despite therapeutic intervention(s). The intestines and its microbial content are prime contributors to this syndrome. The intestinal barrier separates the self (or the so-called “milieu intérior”) from the environment. In the large intestine, the intestinal barrier keeps apart human physiology and the microbiota. The enterocytes and the extracellular mucin layer functions form a complex multilayered structure, facilitating complex bidirectional metabolic and immunological crosstalk. The current review focuses on the intestinal barrier in chronic kidney disease (CKD). Loss of kidney function results in structural and functional alterations of the intestinal barrier, contribution to the syndrome of uremia. Full article
(This article belongs to the Special Issue The Intestine and Uremia)
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12 pages, 1653 KiB  
Article
Differential Toxicity of Cyanobacteria Isolated from Marine Sponges towards Echinoderms and Crustaceans
by Ana Regueiras, Sandra Pereira, Maria Sofia Costa and Vitor Vasconcelos
Toxins 2018, 10(7), 297; https://doi.org/10.3390/toxins10070297 - 18 Jul 2018
Cited by 13 | Viewed by 4591
Abstract
Marine sponges and cyanobacteria have a long history of co-evolution, with documented genome adaptations in cyanobionts. Both organisms are known to produce a wide variety of natural compounds, with only scarce information about novel natural compounds produced by cyanobionts. In the present study, [...] Read more.
Marine sponges and cyanobacteria have a long history of co-evolution, with documented genome adaptations in cyanobionts. Both organisms are known to produce a wide variety of natural compounds, with only scarce information about novel natural compounds produced by cyanobionts. In the present study, we aimed to address their toxicological potential, isolating cyanobacteria (n = 12) from different sponge species from the coast of Portugal (mainland, Azores, and Madeira Islands). After large-scale growth, we obtained both organic and aqueous extracts to perform a series of ecologically-relevant bioassays. In the acute toxicity assay, using nauplii of Artemia salina, only organic extracts showed lethality, especially in picocyanobacterial strains. In the bioassay with Paracentrotus lividus, both organic and aqueous extracts produced embryogenic toxicity (respectively 58% and 36%), pointing to the presence of compounds that interfere with growth factors on cells. No development of pluteus larvae was observed for the organic extract of the strain Chroococcales 6MA13ti, indicating the presence of compounds that affect skeleton formation. In the hemolytic assay, none of the extracts induced red blood cells lysis. Organic extracts, especially from picoplanktonic strains, proved to be the most promising for future bioassay-guided fractionation and compounds isolation. This approach allows us to classify the compounds extracted from the cyanobacteria into effect categories and bioactivity profiles. Full article
(This article belongs to the Special Issue Cyanobacteria and Cyanotoxins: New Advances and Future Challenges)
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21 pages, 6105 KiB  
Article
Biomarker Evaluation and Toxic Effects of an Acute Oral and Systemic Fumonisin Exposure of Pigs with a Special Focus on Dietary Fumonisin Esterase Supplementation
by Hanna Schertz, Sven Dänicke, Jana Frahm, Dian Schatzmayr, Ilse Dohnal, Gerlinde Bichl, Heidi E. Schwartz-Zimmermann, Sonia Colicchia, Gerhard Breves, Jens P. Teifke and Jeannette Kluess
Toxins 2018, 10(7), 296; https://doi.org/10.3390/toxins10070296 - 17 Jul 2018
Cited by 19 | Viewed by 6023
Abstract
The mycotoxin fumonisin B1 (FB1) is a frequent contaminant of feed. It causes a disruption of sphingolipid metabolism and pulmonary, hepatic, and immunological lesions in pigs depending on the exposure scenario. One sensitive biomarker for FB1 exposure is the sphinganine (Sa) to sphingosine [...] Read more.
The mycotoxin fumonisin B1 (FB1) is a frequent contaminant of feed. It causes a disruption of sphingolipid metabolism and pulmonary, hepatic, and immunological lesions in pigs depending on the exposure scenario. One sensitive biomarker for FB1 exposure is the sphinganine (Sa) to sphingosine (So) ratio in blood. The fumonisin esterase FumD, which can be used as a feed additive, converts FB1 into the much less toxic metabolite hydrolyzed FB1 (HFB1). We conducted a single-dose study with barrows allocated to one of five treatments: (1) control (feed, 0.9% NaCl intravenously iv), (2) 139 nmol FB1 or (3) HFB1/kg BW iv, (4) 3425 nmol FB1/kg BW orally (po), or (5) 3321 nmol FB1/kg BW and 240 U FumD/kg feed po. The Sa/So ratio of iv and po FB1 administered groups was significantly elevated in blood and Liquor cerebrospinalis, but no fumonisin-associated differences were reflected in other endpoints. Neither clinical lung affections nor histopathological pulmonary lesions were detected in either group, while some parameters of hematology and clinical biochemistry showed a treatment–time interaction. FumD application resulted in Sa/So ratios comparable to the control, indicating that the enzymatic treatment was effectively preventing the fumonisin-induced disruption of sphingolipid metabolism. Full article
(This article belongs to the Collection Fusarium Toxins – Relevance for Human and Animal Health)
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22 pages, 1734 KiB  
Article
Unilateral Botulinum Neurotoxin-A Injection into the Striatum of C57BL/6 Mice Leads to a Different Motor Behavior Compared with Rats
by Veronica Antipova, Andreas Wree, Carsten Holzmann, Teresa Mann, Nicola Palomero-Gallagher, Karl Zilles, Oliver Schmitt and Alexander Hawlitschka
Toxins 2018, 10(7), 295; https://doi.org/10.3390/toxins10070295 - 17 Jul 2018
Cited by 9 | Viewed by 5539
Abstract
Different morphological changes in the caudate-putamen (CPu) of naïve rats and mice were observed after intrastriatal botulinum neurotoxin-A (BoNT-A) injection. For this purpose we here studied various motor behaviors in mice (n = 46) longitudinally up to 9 months after intrastriatal BoNT-A [...] Read more.
Different morphological changes in the caudate-putamen (CPu) of naïve rats and mice were observed after intrastriatal botulinum neurotoxin-A (BoNT-A) injection. For this purpose we here studied various motor behaviors in mice (n = 46) longitudinally up to 9 months after intrastriatal BoNT-A administration as previously reported for rats, and compared both outcomes. Apomorphine- and amphetamine-induced rotational behavior, spontaneous motor behavior, as well as lateralized neglect were studied in mice after the injection of single doses of BoNT-A into the right CPu, comparing them with sham-injected animals. Unilateral intrastriatal injection of BoNT-A in mice induced significantly increased contralateral apomorphine-induced rotations for 1 to 3 months, as well as significantly increased contralateral amphetamine-induced rotations 1 to 9 months after injection. In rats (n = 28), unilateral BoNT-A injection also induced significantly increased contralateral apomorphine-induced rotations 3 months after injection, but did not provoke amphetamine-induced rotations at all. Lateralized sensorimotor integration, forelimb preference, and forelimb stepping were significantly impaired on the left side. The differences in motor behaviors between rats and mice may be caused by different BoNT-A effects on cholinergic and catecholaminergic fibers in rat and mouse striata, interspecies differences in striatal receptor densities, and different connectomes of the basal ganglia. Full article
(This article belongs to the Special Issue Botulinum Neurotoxins and Nervous System: Future Challenges for Novel Indications)
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21 pages, 3330 KiB  
Article
Multi-Mycotoxin Occurrence in Dairy Cattle Feeds from the Gauteng Province of South Africa: A Pilot Study Using UHPLC-QTOF-MS/MS
by Rumbidzai Changwa, Wilfred Abia, Titus Msagati, Hlengilizwe Nyoni, Khanyisa Ndleve and Patrick Njobeh
Toxins 2018, 10(7), 294; https://doi.org/10.3390/toxins10070294 - 16 Jul 2018
Cited by 35 | Viewed by 6383
Abstract
The indispensable nature of toxigenic fungi and mycotoxins in agricultural systems is of worldwide concern, hence the need for surveillance studies to preserve public health. Thirteen dairy farms were surveyed and 40 dairy feeds of varying nature collected and analyzed for mycotoxins. Estimated [...] Read more.
The indispensable nature of toxigenic fungi and mycotoxins in agricultural systems is of worldwide concern, hence the need for surveillance studies to preserve public health. Thirteen dairy farms were surveyed and 40 dairy feeds of varying nature collected and analyzed for mycotoxins. Estimated levels of aflatoxins (AFs), fumonisin B1 (FB1), ochratoxin A (OTA), citrinin (CIT), zearalenone (ZEN), α-zearalenol (α-ZEL), β-zearalenol (β-ZEL), deoxynivalenol (DON), 3- and 15-acetyl-deoxynivalenol (ADONs), HT-2 toxin (HT-2), and beauvericin (BEA) were established using liquid chromatography-tandem mass spectrometry. Highest frequencies (40/40) were found for AFG2 (range: <LOQ—116.1 ppb), α-ZEL (range: 0.98–13.24 ppb), and β-ZEL (range: 0.73–4.71 ppb), followed by AFB2 at 37/40 (range: <LOQ—23.88 ppb), BEA at 36/40 (range: <LOQ—55.99 ppb), HT-2 at 35/40 (range: <LOQ—312.95 ppb), and FB1 at 34/40 (range: <LOQ—1389.62 ppb). Apart from samples exceeding regulatory limits for total AFs in dairy feeds due to the high amounts of AFG2 and AFB2, levels of other mycotoxins were regarded as safe for dairy production in South Africa. This is the first-time the natural occurrence of the cold climate HT-2 in South African feeds was documented. Persistent co-occurrence of multiple mycotoxins across samples, however, may elicit synergistic and/or additive effects in hosts, hence raising concerns about their impacts and how such interactions may affect the dairy livestock sector. Full article
(This article belongs to the Collection Understanding Mycotoxin Occurrence in Food and Feed Chains)
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10 pages, 542 KiB  
Article
Characterisation of the Mycobiota on the Shell Surface of Table Eggs Acquired from Different Egg-Laying Hen Breeding Systems
by Łukasz Tomczyk, Łukasz Stępień, Monika Urbaniak, Tomasz Szablewski, Renata Cegielska-Radziejewska and Kinga Stuper-Szablewska
Toxins 2018, 10(7), 293; https://doi.org/10.3390/toxins10070293 - 16 Jul 2018
Cited by 27 | Viewed by 5492
Abstract
Microbial safety is an important factor contributing to the egg quality. During egg acquisition, there is significant risk of contamination of the eggshell surface with microscopic fungi. Mycelial hyphae may grow on the eggshell surface and penetrate into the egg content. However, there [...] Read more.
Microbial safety is an important factor contributing to the egg quality. During egg acquisition, there is significant risk of contamination of the eggshell surface with microscopic fungi. Mycelial hyphae may grow on the eggshell surface and penetrate into the egg content. However, there is no information on the populations of microscopic fungi on the eggshell surface and, consequently, on possible production of mycotoxins. Therefore, the aim of the study was to identify the species of microscopic fungi present on the eggshell surface acquired from different breeding systems and to measure the number of selected mycotoxins. The qualitative analysis resulted in the identification of 41 isolates on the surface of eggs. There were 7 isolates from the organic production system, 11 from the free-range production system, 14 from the deep litter indoor housing system and 9 from the cage farming production system. The research proved that the diversification in the population of mycobiota on the eggshells depended on the egg-laying hen breeding system. The microscopic fungi isolated from the eggshells included toxigenic and pathogenic species such as Fusarium culmorum and F. equiseti. As the egg storage time increased, fungi, including the pathogenic species, penetrated through the eggshells. In consequence, mycotoxins were identified in the egg whites. Type-A and type-B trichothecenes were found in the eggshell samples containing F. culmorum. Full article
(This article belongs to the Section Mycotoxins)
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23 pages, 1605 KiB  
Review
Studying Smaller and Neglected Organisms in Modern Evolutionary Venomics Implementing RNASeq (Transcriptomics)—A Critical Guide
by Björn Marcus Von Reumont
Toxins 2018, 10(7), 292; https://doi.org/10.3390/toxins10070292 - 16 Jul 2018
Cited by 27 | Viewed by 5328
Abstract
Venoms are evolutionary key adaptations that species employ for defense, predation or competition. However, the processes and forces that drive the evolution of venoms and their toxin components remain in many aspects understudied. In particular, the venoms of many smaller, neglected (mostly invertebrate) [...] Read more.
Venoms are evolutionary key adaptations that species employ for defense, predation or competition. However, the processes and forces that drive the evolution of venoms and their toxin components remain in many aspects understudied. In particular, the venoms of many smaller, neglected (mostly invertebrate) organisms are not characterized in detail, especially with modern methods. For the majority of these taxa, even their biology is only vaguely known. Modern evolutionary venomics addresses the question of how venoms evolve by applying a plethora of -omics methods. These recently became so sensitive and enhanced that smaller, neglected organisms are now more easily accessible to comparatively study their venoms. More knowledge about these taxa is essential to better understand venom evolution in general. The methodological core pillars of integrative evolutionary venomics are genomics, transcriptomics and proteomics, which are complemented by functional morphology and the field of protein synthesis and activity tests. This manuscript focuses on transcriptomics (or RNASeq) as one toolbox to describe venom evolution in smaller, neglected taxa. It provides a hands-on guide that discusses a generalized RNASeq workflow, which can be adapted, accordingly, to respective projects. For neglected and small taxa, generalized recommendations are difficult to give and conclusions need to be made individually from case to case. In the context of evolutionary venomics, this overview highlights critical points, but also promises of RNASeq analyses. Methodologically, these concern the impact of read processing, possible improvements by perfoming multiple and merged assemblies, and adequate quantification of expressed transcripts. Readers are guided to reappraise their hypotheses on venom evolution in smaller organisms and how robustly these are testable with the current transcriptomics toolbox. The complementary approach that combines particular proteomics but also genomics with transcriptomics is discussed as well. As recently shown, comparative proteomics is, for example, most important in preventing false positive identifications of possible toxin transcripts. Finally, future directions in transcriptomics, such as applying 3rd generation sequencing strategies to overcome difficulties by short read assemblies, are briefly addressed. Full article
(This article belongs to the Section Animal Venoms)
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8 pages, 2163 KiB  
Article
Label-Free Optical Detection of Mycotoxins Using Specific Aptamers Immobilized on Gold Nanostructures
by Ali Ghanim Al-Rubaye, Alexei Nabok, Gaelle Catanante, Jean-Louis Marty, Eszter Takács and András Székács
Toxins 2018, 10(7), 291; https://doi.org/10.3390/toxins10070291 - 16 Jul 2018
Cited by 26 | Viewed by 5300
Abstract
This work focuses on the development of the novel label-free optical apta-sensors for detection of mycotoxins. A highly sensitive analytical method of total internal reflection ellipsometry (TIRE) combined with Localized Surface Plasmon Resonance (LSPR) phenomenon in nano-structured gold films was exploited here for [...] Read more.
This work focuses on the development of the novel label-free optical apta-sensors for detection of mycotoxins. A highly sensitive analytical method of total internal reflection ellipsometry (TIRE) combined with Localized Surface Plasmon Resonance (LSPR) phenomenon in nano-structured gold films was exploited here for the first time for detection of aflatoxin B1 and M1 in direct assay with specific aptamers immobilized on the surface of gold. The achieved detection of low molecular weight molecules, such as aflatoxin B1 and M1, in a wide range of concentrations from 100 ng/mL down to 0.01 ng/mL is remarkable for the LSPR method. The study of binding kinetics of aflatoxin molecules to their respective aptamers using dynamic TIRE measurements yielded the values of affinity constants in the range of 10−8–10−7 mol, which is characteristic for highly specific aptamer/target interactions similar to that for monoclonal antibodies. The effect of aptamers’ DNA chain length on their binding characteristics was analyzed. Full article
(This article belongs to the Special Issue Advanced Sensors for Toxins)
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12 pages, 1340 KiB  
Article
The Effect of Cyanobacterial LPS Antagonist (CyP) on Cytokines and Micro-RNA Expression Induced by Porphyromonas gingivalis LPS
by Monica Molteni, Annalisa Bosi and Carlo Rossetti
Toxins 2018, 10(7), 290; https://doi.org/10.3390/toxins10070290 - 16 Jul 2018
Cited by 12 | Viewed by 4491
Abstract
Lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg-LPS) is a key bacterial structure involved in the maintenance of a chronic pro-inflammatory environment during periodontitis. Similar to other gram-negative LPS, Pg-LPS induces the release of pro-inflammatory cytokines through interaction with Toll-Like Receptor 4 (TLR4) and is [...] Read more.
Lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg-LPS) is a key bacterial structure involved in the maintenance of a chronic pro-inflammatory environment during periodontitis. Similar to other gram-negative LPS, Pg-LPS induces the release of pro-inflammatory cytokines through interaction with Toll-Like Receptor 4 (TLR4) and is able to stimulate negative TLR4 regulatory pathways, such as those involving microRNA (miRNA). In this work, we employed CyP, an LPS with TLR4-MD2 antagonist activity obtained from the cyanobacterium Oscillatoria planktothrix FP1, to study the effects on pro-inflammatory cytokine production and miRNA expression in human monocytic THP-1 cells stimulated with Pg-LPS or E. coli LPS (Ec-LPS). Results showed that CyP inhibited TNF-α, IL-1β and IL-8 expression more efficiently when co-incubated with Pg-LPS rather than with Ec-LPS. The inhibition of pro-inflammatory cytokine production was maintained even when CyP was added 2 h after LPS. The analysis of the effects of CyP on miRNA expression showed that, although being an antagonist, CyP did not inhibit miR-146a induced by Pg-LPS or Ec-LPS, whereas it significantly inhibited miR-155 only in the cultures stimulated with Ec-LPS. These results suggest that CyP may modulate the pro-inflammatory response induced by Pg-LPS, not only by blocking TLR4-MD2 complex, but also by preserving miR-146a expression. Full article
(This article belongs to the Special Issue Lipopolysaccharide: Bacterial Endotoxin)
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14 pages, 2617 KiB  
Article
Establishment of a New Zealand White Rabbit Model for Lethal Toxin (LT) Challenge and Efficacy of Monoclonal Antibody 5E11 in the LT-Challenged Rabbit Model
by Duanyang Zhang, Weicen Liu, Zhonghua Wen, Bing Li, Shuling Liu, Jianmin Li and Wei Chen
Toxins 2018, 10(7), 289; https://doi.org/10.3390/toxins10070289 - 12 Jul 2018
Cited by 9 | Viewed by 4764
Abstract
Anthrax caused by Bacillus anthracis is a lethal infectious disease, especially when inhaled, and the mortality rate approaches 100% without treatment. The anthrax antitoxin monoclonal antibody (MAb) 5E11 is a humanized antibody that targets the anthrax protective antigen (PA). The efficacy of 5E11 [...] Read more.
Anthrax caused by Bacillus anthracis is a lethal infectious disease, especially when inhaled, and the mortality rate approaches 100% without treatment. The anthrax antitoxin monoclonal antibody (MAb) 5E11 is a humanized antibody that targets the anthrax protective antigen (PA). The efficacy of 5E11 needs proper animal models. However, anthrax spores are extremely dangerous, so experiments must be conducted under Biosafety Level 3 conditions. Considering the critical effects of lethal toxin (LT) on hosts during infection, we report the establishment of a LT-challenged rabbit model, which caused 100% mortality with a dose of 2 mg PA + 1 mg LF, while a 4 mg PA + 2 mg LF challenge could limit death to within three days. Then, we evaluated 5E11 efficacy against LT. A prophylactic study showed that the i.v. administration of 40 mg/kg 5E11 four days before lethal dose LT challenge could lead to 100% survival. In therapeutic studies, the i.v. administration of 40 mg/kg 5E11 10 min after lethal dose LT challenge could provide complete protection. Overall, we developed a new LT-challenged rabbit model, and our results indicate that 5E11 shows potential for the clinical application in anthrax treatment. Full article
(This article belongs to the Collection Anthrax Toxins)
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11 pages, 1660 KiB  
Article
Detection of the Potential Inactivation of Tetrodotoxin by Lactic Acid Bacterial Exopolysaccharide
by Nguyen Hoang Khue Tu, Nghe Van Dat, Le Van Canh and Doan Thi Thanh Vinh
Toxins 2018, 10(7), 288; https://doi.org/10.3390/toxins10070288 - 12 Jul 2018
Cited by 10 | Viewed by 5040
Abstract
Screening for compounds that can neutralize the toxicity of tetrodotoxin (TTX) or reduce its negative effects is necessary. Our study tested the TTX detoxification capacity of exopolysaccharide (EPS) extracted from lactic acid bacteria. EPS of Leuconostoc mesenteroides N3 isolated from the Vung Tau [...] Read more.
Screening for compounds that can neutralize the toxicity of tetrodotoxin (TTX) or reduce its negative effects is necessary. Our study tested the TTX detoxification capacity of exopolysaccharide (EPS) extracted from lactic acid bacteria. EPS of Leuconostoc mesenteroides N3 isolated from the Vung Tau sea (Vietnam), Lactobacillus plantarum PN05, and Lactobacillus rhamnosus PN04 were used in the study. To more completely evaluate the importance of EPS in detoxification, EPS samples of Leuconostoc mesenteroides N3, Lactobacillus plantarum PN05 and Lactobacillus rhamnosus PN04 were also tested. The majority of EPS of these bacteria contained glucose; this was observed using thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) analysis. As observed with FTIR analysis, only EPS of Lactobacillus plantarum PN05 contained methyl groups. The results indicated that detoxification of TTX in mice could be obtained at an optimal dose of 248 µg EPS from Leuconostoc mesenteroides incubated with 54 µg cuprous oxide for 40 min or 148 µg EPS Lactobacillus rhamnosus incubated with 55 µg cuprous oxide for 40 min, while EPS from Lactobacillus plantarum showed TTX detoxification capacity without cuprous oxide combination. Consequently, EPS from Lactobacillus plantarum PN05 can be used in TTX prevention. This is the first report on the importance of lactic acid bacteria in TTX detoxification. Full article
(This article belongs to the Special Issue Tetrodotoxins)
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18 pages, 461 KiB  
Review
Gut Microbiota and Cardiovascular Uremic Toxicities
by Manuel T. Velasquez, Patricia Centron, Ian Barrows, Rama Dwivedi and Dominic S. Raj
Toxins 2018, 10(7), 287; https://doi.org/10.3390/toxins10070287 - 11 Jul 2018
Cited by 62 | Viewed by 13622
Abstract
Cardiovascular disease (CVD) remains a major cause of high morbidity and mortality in patients with chronic kidney disease (CKD). Numerous CVD risk factors in CKD patients have been described, but these do not fully explain the high pervasiveness of CVD or increased mortality [...] Read more.
Cardiovascular disease (CVD) remains a major cause of high morbidity and mortality in patients with chronic kidney disease (CKD). Numerous CVD risk factors in CKD patients have been described, but these do not fully explain the high pervasiveness of CVD or increased mortality rates in CKD patients. In CKD the loss of urinary excretory function results in the retention of various substances referred to as “uremic retention solutes”. Many of these molecules have been found to exert toxicity on virtually all organ systems of the human body, leading to the clinical syndrome of uremia. In recent years, an increasing body of evidence has been accumulated that suggests that uremic toxins may contribute to an increased cardiovascular disease (CVD) burden associated with CKD. This review examined the evidence from several clinical and experimental studies showing an association between uremic toxins and CVD. Special emphasis is addressed on emerging data linking gut microbiota with the production of uremic toxins and the development of CKD and CVD. The biological toxicity of some uremic toxins on the myocardium and the vasculature and their possible contribution to cardiovascular injury in uremia are also discussed. Finally, various therapeutic interventions that have been applied to effectively reduce uremic toxins in patients with CKD, including dietary modifications, use of prebiotics and/or probiotics, an oral intestinal sorbent that adsorbs uremic toxins and precursors, and innovative dialysis therapies targeting the protein-bound uremic toxins are also highlighted. Future studies are needed to determine whether these novel therapies to reduce or remove uremic toxins will reduce CVD and related cardiovascular events in the long-term in patients with chronic renal failure. Full article
(This article belongs to the Special Issue Uremia and Cardiovascular Disease)
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15 pages, 1795 KiB  
Article
Synergistic Effects of Influenza and Staphylococcus aureus Toxins on Inflammation Activation and Cytotoxicity in Human Monocytic Cell Lines
by Marion Jeannoel, Jean-Sebastien Casalegno, Michèle Ottmann, Cédric Badiou, Oana Dumitrescu, Bruno Lina and Gérard Lina
Toxins 2018, 10(7), 286; https://doi.org/10.3390/toxins10070286 - 11 Jul 2018
Cited by 13 | Viewed by 4295
Abstract
In patients with influenza, morbidity and mortality are strongly influenced by infections with Staphylococcus aureus producing high amounts of certain toxins. Here we tested the impact of influenza virus on the pro-inflammatory and cytotoxic actions of a panel of S. aureus virulence factors, [...] Read more.
In patients with influenza, morbidity and mortality are strongly influenced by infections with Staphylococcus aureus producing high amounts of certain toxins. Here we tested the impact of influenza virus on the pro-inflammatory and cytotoxic actions of a panel of S. aureus virulence factors, including Panton-Valentine Leucocidin (PVL), phenol-soluble modulin α1 (PSMα1) and 3 (PSMα3), α-hemolysin (Hla), and cell wall components, i.e., heat-killed S. aureus (HKSA) and protein A. We initially screened for potential synergic interactions using a standardized in vitro model in influenza-infected continuous human monocytic cell lines. Then we tested the identified associations using an ex vivo model in influenza-infected human monocytes freshly isolated from blood. Co-exposure to influenza virus and HKSA, PVL, PSMα1, and PSMα3 increased NF-κB/AP-1 pathway activation in THP1-XBlue cells, and co-exposure to influenza virus and PVL increased cytotoxicity in U937 cells. In monocytes isolated from blood, the synergy between influenza virus and HKSA was confirmed based on cytokine production (TNF-α, IL-1β, IL-6), and co-exposure to influenza virus and Hla-increased cytotoxicity. Our findings suggest that influenza virus potentiates the pro-inflammatory action of HKSA and contributes to the cytotoxicity of Hla on monocytes. Synergic interactions identified in the cell-line model must be cautiously interpreted since few were relevant in the ex vivo model. Full article
(This article belongs to the Special Issue Leukotoxins)
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15 pages, 1978 KiB  
Article
Complexation of the Mycotoxin Cyclopiazonic Acid with Lanthanides Yields Luminescent Products
by Chris M. Maragos
Toxins 2018, 10(7), 285; https://doi.org/10.3390/toxins10070285 - 10 Jul 2018
Cited by 6 | Viewed by 4203
Abstract
Cycopiazonic acid (CPA) is a neurotoxin that acts through inhibition of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA). CPA blocks the calcium access channel of the enzyme. The inhibition may involve the binding of CPA with a divalent cation such as Mg2+ [...] Read more.
Cycopiazonic acid (CPA) is a neurotoxin that acts through inhibition of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA). CPA blocks the calcium access channel of the enzyme. The inhibition may involve the binding of CPA with a divalent cation such as Mg2+. The potential for CPA to act as a chelator also has implications for methods to detect this toxin. Certain of the lanthanide metals undergo a dramatic increase in luminescence upon coordination with small molecules that can transfer excitation energy to the metal. This report is the first to describe the coordination of CPA with lanthanide metals, resulting in a substantial enhancement of their luminescence. The luminescence expressed was dependent upon the type of lanthanide, its concentration, and the environment (solvent, water content, pH). Based upon the phenomenon, a competitive assay was also developed wherein terbium (Tb3+) and a series of metal cations competed for binding with CPA. With increasing cation concentration, the luminescence of the CPA/Tb3+ complex was inhibited. The chlorides of ten metals were tested. Inhibition was best with Cu2+, followed by Co2+, Al3+, Fe3+, Mn2+, Au3+, Mg2+, and Ca2+. Two cations in oxidation state one (Na+, K+) did not inhibit the interaction significantly. The interaction of CPA with lanthanides provides a novel recognition assay for this toxin. It also provides a novel way to probe the binding of CPA to metals, giving insights into CPA’s mechanism of action. Full article
(This article belongs to the Collection Biorecognition Assays for Mycotoxins)
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12 pages, 1128 KiB  
Article
Toxicity Assay for Citrinin, Zearalenone and Zearalenone-14-Sulfate Using the Nematode Caenorhabditis elegans as Model Organism
by Julia Keller, Antje Borzekowski, Hajo Haase, Ralph Menzel, Liliane Rueß and Matthias Koch
Toxins 2018, 10(7), 284; https://doi.org/10.3390/toxins10070284 - 9 Jul 2018
Cited by 15 | Viewed by 5682
Abstract
To keep pace with the rising number of detected mycotoxins, there is a growing need for fast and reliable toxicity tests to assess potential threats to food safety. Toxicity tests with the bacterial-feeding nematode Caenorhabditis elegans as the model organism are well established. [...] Read more.
To keep pace with the rising number of detected mycotoxins, there is a growing need for fast and reliable toxicity tests to assess potential threats to food safety. Toxicity tests with the bacterial-feeding nematode Caenorhabditis elegans as the model organism are well established. In this study the C. elegans wildtype strain N2 (var. Bristol) was used to investigate the toxic effects of the food-relevant mycotoxins citrinin (CIT) and zearalenone-14-sulfate (ZEA-14-S) and zearalenone (ZEA) on different life cycle parameters including reproduction, thermal and oxidative stress resistance and lifespan. The metabolization of the mycotoxins by the nematodes in vivo was investigated using HPLC-MS/MS. ZEA was metabolized in vivo to the reduced isomers α-zearalenol (α-ZEL) and β-ZEL. ZEA-14-S was reduced to α-/β-ZEL-14-sulfate and CIT was metabolized to mono-hydroxylated CIT. All mycotoxins tested led to a significant decrease in the number of nematode offspring produced. ZEA and CIT displayed negative effects on stress tolerance levels and for CIT an additional shortening of the mean lifespan was observed. In the case of ZEA-14-S, however, the mean lifespan was prolonged. The presented study shows the applicability of C. elegans for toxicity testing of emerging food mycotoxins for the purpose of assigning potential health threats. Full article
(This article belongs to the Section Mycotoxins)
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16 pages, 1450 KiB  
Article
Multi-Toxin Occurrences in Ten French Water Resource Reservoirs
by Frederic Pitois, Jutta Fastner, Christelle Pagotto and Magali Dechesne
Toxins 2018, 10(7), 283; https://doi.org/10.3390/toxins10070283 - 9 Jul 2018
Cited by 31 | Viewed by 4179
Abstract
Cyanobacteria are known to produce a wide array of metabolites, including various classes of toxins. Among these, hepatotoxins (Microcystins), neurotoxins (Anatoxin-A and PSP toxins) or cytotoxins (Cylindrospermopsins) have been subjected to numerous, individual studies during the past twenty years. Reports of toxins co-occurrences, [...] Read more.
Cyanobacteria are known to produce a wide array of metabolites, including various classes of toxins. Among these, hepatotoxins (Microcystins), neurotoxins (Anatoxin-A and PSP toxins) or cytotoxins (Cylindrospermopsins) have been subjected to numerous, individual studies during the past twenty years. Reports of toxins co-occurrences, however, remain scarce in the literature. The present work is an inventory of cyanobacteria with a particular focus on Nostocales and their associated toxin classes from 2007 to 2010 in ten lakes used for drinking water production in France. The results show that potential multiple toxin producing species are commonly encountered in cyanobacteria populations. Individual toxin classes were detected in 75% of all samples. Toxin co-occurrences appeared in 40% of samples as two- or three-toxin combinations (with 35% for the microcystins–anatoxin combination), whereas four-toxin class combinations only appeared in 1% of samples. Toxin co-occurrences could be partially correlated to species composition and water temperature. Peak concentrations however could never be observed simultaneously and followed distinct, asymmetrical distribution patterns. As observations are the key for preventive management and risk assessment, these results indicate that water monitoring should search for all four toxin classes simultaneously instead of focusing on the most frequent toxins, i.e., microcystins. Full article
(This article belongs to the Special Issue Cyanobacteria and Cyanotoxins: New Advances and Future Challenges)
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14 pages, 7560 KiB  
Article
Distribution of Tetrodotoxin in the New Zealand Clam, Paphies australis, Established Using Immunohistochemistry and Liquid Chromatography-Tandem Quadrupole Mass Spectrometry
by Laura Biessy, Kirsty F. Smith, Michael J. Boundy, Stephen C. Webb, Ian Hawes and Susanna A. Wood
Toxins 2018, 10(7), 282; https://doi.org/10.3390/toxins10070282 - 6 Jul 2018
Cited by 14 | Viewed by 5298
Abstract
Tetrodotoxin (TTX) is one of the most potent neurotoxins known. It was originally thought to only occur in puffer fish but has now been identified in twelve different classes of freshwater and marine organisms, including bivalves. Despite being one of the world’s most [...] Read more.
Tetrodotoxin (TTX) is one of the most potent neurotoxins known. It was originally thought to only occur in puffer fish but has now been identified in twelve different classes of freshwater and marine organisms, including bivalves. Despite being one of the world’s most studied biotoxins, its origin remains uncertain. There is contradictory evidence regarding the source of TTX and its pathway through food webs. To date, the distribution of TTX has not been examined in bivalves. In the present study, 48 Paphies australis, a TTX-containing clam species endemic to New Zealand, were collected. Thirty clams were dissected, and organs and tissues pooled into five categories (siphons, digestive gland, adductor muscles, and the ‘rest’) and analyzed for TTX using liquid chromatography-mass spectrometry (LC-MS). The micro-distribution of TTX was visualized in the remaining 18 individuals using an immunohistological technique incorporating a TTX-specific monoclonal antibody. The LC-MS analysis revealed that siphons contained the highest concentrations of TTX (mean 403.8 µg/kg). Immunohistochemistry analysis showed TTX in the outer cells of the siphons, but also in the digestive system, foot, and gill tissue. Observing TTX in organs involved in feeding provides initial evidence to support the hypothesis of an exogenous source in P. australis. Full article
(This article belongs to the Special Issue Tetrodotoxins)
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13 pages, 1466 KiB  
Review
Interaction between Insects, Toxins, and Bacteria: Have We Been Wrong So Far?
by Guillaume Tetreau
Toxins 2018, 10(7), 281; https://doi.org/10.3390/toxins10070281 - 6 Jul 2018
Cited by 14 | Viewed by 6645
Abstract
Toxins are a major virulence factor produced by many pathogenic bacteria. In vertebrates, the response of hosts to the bacteria is inseparable from the response to the toxins, allowing a comprehensive understanding of this tripartite host-pathogen-toxin interaction. However, in invertebrates, this interaction has [...] Read more.
Toxins are a major virulence factor produced by many pathogenic bacteria. In vertebrates, the response of hosts to the bacteria is inseparable from the response to the toxins, allowing a comprehensive understanding of this tripartite host-pathogen-toxin interaction. However, in invertebrates, this interaction has been investigated by two complementary but historically distinct fields of research: toxinology and immunology. In this article, I highlight how such dichotomy between these two fields led to a biased, or even erroneous view of the ecology and evolution of the interaction between insects, toxins, and bacteria. I focus on the reason behind such a dichotomy, on how to bridge the fields together, and on confounding effects that could bias the outcome of the experiments. Finally, I raise four questions at the border of the two fields on the cross-effects between toxins, bacteria, and spores that have been largely underexplored to promote a more comprehensive view of this interaction. Full article
(This article belongs to the Special Issue Toxins and Immunology)
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11 pages, 2269 KiB  
Article
Indoxyl Sulfate, a Uremic Toxin, Stimulates Reactive Oxygen Species Production and Erythrocyte Cell Death Supposedly by an Organic Anion Transporter 2 (OAT2) and NADPH Oxidase Activity-Dependent Pathways
by Gabriela Ferreira Dias, Natalia Borges Bonan, Thiago Maass Steiner, Sara Soares Tozoni, Silvia Rodrigues, Lia Sumie Nakao, Viktoriya Kuntsevich, Roberto Pecoits Filho, Peter Kotanko and Andréa N. Moreno-Amaral
Toxins 2018, 10(7), 280; https://doi.org/10.3390/toxins10070280 - 5 Jul 2018
Cited by 52 | Viewed by 5374
Abstract
It is hypothesized that the uremic toxin indoxyl sulfate (IS) plays a role in the pathogenesis of renal anemia. To further explore that hypothesis, we examined the effects of IS on reactive oxygen species (ROS) production, levels of reduced glutathione (GSH), and erythrocyte [...] Read more.
It is hypothesized that the uremic toxin indoxyl sulfate (IS) plays a role in the pathogenesis of renal anemia. To further explore that hypothesis, we examined the effects of IS on reactive oxygen species (ROS) production, levels of reduced glutathione (GSH), and erythrocyte death (eryptosis) in red blood cells (RBC) from healthy controls (CON-RBC) and hemodialyzed patients (HD-RBC), respectively. RBC were incubated either in either TRIS-Glc-BSA buffer or IS at concentrations of 0.01, 0.09, and 0.17 mM, respectively. We measured ROS generation (expressed as % of DCFH-DA positive RBC), eryptosis (expressed as % of annexin-V positive RBC), and GSH levels after 6, 12, and 24 h. When incubated in buffer, ROS production was approximately seven-fold higher at all time points HD-RBC when compared to CON-RBC. Incubation with IS increased ROS production in CON-RBS dose-dependently up to 10-fold. Eryptosis in buffer-incubated HD-RBC was up to seven-fold higher as compared to COB-RBC. Incubation of CON-RBC with IS increased the eryptosis rate dose-dependently up to 6-fold. Pretreatment of CON-RBC with the organic anion transporter 2 (OAT2) specific inhibitor ketoprofen or with NADPH oxidase inhibitor diphenyleneiodonium-Cl blunted the IS effect on both ROS production and eryptosis induction. While GSH levels in HD-RBC were reduced when compared to CON-RBC, they were not affected by IS incubation. In summary, IS increases ROS generation and eryptosis in CON-RBC by an activity dependent of the IS influx through OAT2, and NADPH oxidase activity-dependent, and a GSH-independent mechanism. These findings lend support to a putative role of IS in the pathogenesis of renal anemia. Full article
(This article belongs to the Section Uremic Toxins)
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22 pages, 339 KiB  
Review
Overview on the Mycotoxins Incidence in Serbia in the Period 2004–2016
by Bozidar Udovicki, Kris Audenaert, Sarah De Saeger and Andreja Rajkovic
Toxins 2018, 10(7), 279; https://doi.org/10.3390/toxins10070279 - 5 Jul 2018
Cited by 55 | Viewed by 5201
Abstract
With an average annual production of 6.9 M tonnes and 2.5 M tonnes of maize and wheat respectively, Serbia is one of the main grain producers and exporters in Europe. Cereals are also the major staple food in Serbian diet. In view of [...] Read more.
With an average annual production of 6.9 M tonnes and 2.5 M tonnes of maize and wheat respectively, Serbia is one of the main grain producers and exporters in Europe. Cereals are also the major staple food in Serbian diet. In view of the high cereal consumption, for human and animal nutrition, the presence of mycotoxins entails a high public health risk of chronic exposure to mycotoxins. This study provides an overview of the incidence of predominant mycotoxins, mainly in cereal and dairy products, in Serbia, in the 2004–2016, using data reported in the scientific literature. The study demonstrated that the total prevalence of aflatoxins was 62.9% (n = 12,517) with 26.2% of the samples exceeding the EU limits during this period. Results obtained for T-2/HT-2 (n = 523), deoxynivalenol (n = 2907), fumonisins (n = 998), zearalenone (n = 689) and ochratoxin A (n = 740) indicated the prevalence of 45.5%, 42.9%, 63.3%, 39.3% and 28.1%, respectively. For these mycotoxins, the EU limits were less frequently exceeded. Comprehensive collection and analysis of all accessible information reviewed in this paper showed moderate incidence and prevalence of mycotoxins in Serbia, with an exception of the 2012 drought year and the 2014 flood year. Full article
(This article belongs to the Section Mycotoxins)
20 pages, 2026 KiB  
Review
Engineering Botulinum Toxins to Improve and Expand Targeting and SNARE Cleavage Activity
by Elena Fonfria, Mark Elliott, Matthew Beard, John A. Chaddock and Johannes Krupp
Toxins 2018, 10(7), 278; https://doi.org/10.3390/toxins10070278 - 4 Jul 2018
Cited by 23 | Viewed by 7102
Abstract
Botulinum neurotoxins (BoNTs) are highly successful protein therapeutics. Over 40 naturally occurring BoNTs have been described thus far and, of those, only 2 are commercially available for clinical use. Different members of the BoNT family present different biological properties but share a similar [...] Read more.
Botulinum neurotoxins (BoNTs) are highly successful protein therapeutics. Over 40 naturally occurring BoNTs have been described thus far and, of those, only 2 are commercially available for clinical use. Different members of the BoNT family present different biological properties but share a similar multi-domain structure at the molecular level. In nature, BoNTs are encoded by DNA in producing clostridial bacteria and, as such, are amenable to recombinant production through insertion of the coding DNA into other bacterial species. This, in turn, creates possibilities for protein engineering. Here, we review the production of BoNTs by the natural host and also recombinant production approaches utilised in the field. Applications of recombinant BoNT-production include the generation of BoNT-derived domain fragments, the creation of novel BoNTs with improved performance and enhanced therapeutic potential, as well as the advancement of BoNT vaccines. In this article, we discuss site directed mutagenesis, used to affect the biological properties of BoNTs, including approaches to alter their binding to neurons and to alter the specificity and kinetics of substrate cleavage. We also discuss the target secretion inhibitor (TSI) platform, in which the neuronal binding domain of BoNTs is substituted with an alternative cellular ligand to re-target the toxins to non-neuronal systems. Understanding and harnessing the potential of the biological diversity of natural BoNTs, together with the ability to engineer novel mutations and further changes to the protein structure, will provide the basis for increasing the scope of future BoNT-based therapeutics. Full article
(This article belongs to the Special Issue Novel BoNTs and Toxin Engineering)
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9 pages, 532 KiB  
Article
Effects of Dietary Astaxanthin Supplementation on Energy Budget and Bioaccumulation in Procambarus clarkii (Girard, 1852) Crayfish under Microcystin-LR Stress
by Zhenhua An, Yingying Zhang and Longshen Sun
Toxins 2018, 10(7), 277; https://doi.org/10.3390/toxins10070277 - 4 Jul 2018
Cited by 7 | Viewed by 3350
Abstract
This research aimed to study the effects of astaxanthin on energy budget and bioaccumulation of microcystin-leucine-arginine (microcystin-LR) in the crayfish Procambarus clarkii (Girard, 1852). The crayfish (21.13 ± 4.6 g) were cultured under microcystin-LR stress (0.025 mg/L) and were fed with fodders containing [...] Read more.
This research aimed to study the effects of astaxanthin on energy budget and bioaccumulation of microcystin-leucine-arginine (microcystin-LR) in the crayfish Procambarus clarkii (Girard, 1852). The crayfish (21.13 ± 4.6 g) were cultured under microcystin-LR stress (0.025 mg/L) and were fed with fodders containing astaxanthin (0, 3, 6, 9, and 12 mg/g) for 8 weeks in glass tanks (350 mm × 450 mm × 150 mm). Accumulations of microcystin-LR were measured in different organs of P. clarkii. The results suggested that astaxanthin can significantly improve the survival rate and specific growth rate (SGR) of P. clarkii (p < 0.05). The dietary astaxanthin supplement seems to block the bioaccumulation of microcystin-LR in the hepatopancreas and ovaries of P. clarkii to some extent (p < 0.05). Astaxanthin content of 9–12 mg/g in fodder can be a practical and economic choice. Full article
(This article belongs to the Special Issue Cyanobacteria and Cyanotoxins: New Advances and Future Challenges)
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10 pages, 3414 KiB  
Article
Low Levels of Chito-Oligosaccharides Are Not Effective in Reducing Deoxynivalenol Toxicity in Swine Jejunal Explants
by Juliana Gerez, Letícia Buck, Victor Hugo Marutani, Caroline Maria Calliari and Ana Paula Bracarense
Toxins 2018, 10(7), 276; https://doi.org/10.3390/toxins10070276 - 4 Jul 2018
Cited by 10 | Viewed by 3833
Abstract
Deoxynivalenol (DON) is a mycotoxin that affects the intestinal morphology of animals, impairing nutrient intake and growth. On the other hand, dietary supplementation with functional oligosaccharides as chito-oligosaccharides (COS) has shown positive effects on the intestinal health of piglets. Therefore, the objective of [...] Read more.
Deoxynivalenol (DON) is a mycotoxin that affects the intestinal morphology of animals, impairing nutrient intake and growth. On the other hand, dietary supplementation with functional oligosaccharides as chito-oligosaccharides (COS) has shown positive effects on the intestinal health of piglets. Therefore, the objective of the present study was to evaluate the effect of low doses of COS in preventing DON-induced intestinal histological changes, using a swine jejunal explant technique. The intestinal explants were incubated at 37 °C in culture medium for 4 h and exposed to the following treatments: (a) control (only culture medium), (b) DON (10 µM), (c) 25COS (0.025 mg·mL−1 of COS); (d) 50COS (0.05 mg·mL−1 of COS); (e) 25COS plus DON (25COS + DON); (f) 50COS plus DON (50COS + DON). Explants exposed to COS presented intestinal morphology similar to control samples. DON induced a significant decrease in the histological score as a consequence of moderate to severe histological changes (apical necrosis, villi atrophy, and fusion) and a significant decrease in morphometric parameters (villi height, crypt depth, villi height:crypt depth ratio, and goblet cells density). The intestinal morphology of samples exposed to COS + DON remained similar to DON treatment. In conclusion, low levels of COS did not counteract DON-induced intestinal lesions. Full article
(This article belongs to the Special Issue Effects of Mycotoxins on the Intestine)
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19 pages, 2940 KiB  
Article
Microcystin Content in Phytoplankton and in Small Fish from Eutrophic Nyanza Gulf, Lake Victoria, Kenya
by Benard Mucholwa Simiyu, Steve Omondi Oduor, Thomas Rohrlack, Lewis Sitoki and Rainer Kurmayer
Toxins 2018, 10(7), 275; https://doi.org/10.3390/toxins10070275 - 3 Jul 2018
Cited by 43 | Viewed by 6773
Abstract
The human health risks posed by exposure to cyanobacterial toxins such as microcystin (MC) through water and fish consumption remain poorly described. During the last two decades, coastal regions of Lake Victoria such as Nyanza Gulf (Kisumu Bay) have shown severe signs of [...] Read more.
The human health risks posed by exposure to cyanobacterial toxins such as microcystin (MC) through water and fish consumption remain poorly described. During the last two decades, coastal regions of Lake Victoria such as Nyanza Gulf (Kisumu Bay) have shown severe signs of eutrophication with blooms formed by Microcystis producing MC. In this study, the spatial variability in MC concentration in Kisumu Bay was investigated which was mostly caused by Microcystis buoyancy and wind drifting. Small fish (<6 cm) mainly composed of Rastrineobola argentea were examined for MC content by means of biological methods such as ELISA and protein phosphatase inhibition assay (PPIA) and partly by chemical-analytical methods such as LC-MS/MS. Overall, the MC content in small fish was related to the MC content observed in the seston. When comparing the MC content in the seston in relation to dry weight with the MC content in small fish the latter was found three orders of magnitude decreased. On average, the ELISA-determined MC contents exceeded the PPIA-determined MC contents by a factor of 8.2 ± 0.5 (SE) while the MC contents as determined by LC-MS/MS were close to the detection limit. Using PPIA, the MC content varied from 25–109 (mean 62 ± 7) ng/g fish dry weight in Kisumu Bay vs. 14 ± 0.8 ng MC/g in the more open water of L. Victoria at Rusinga channel. Drying the fish under the sun showed little effect on MC content, although increased humidity might indirectly favor photocatalyzed MC degradation. Full article
(This article belongs to the Special Issue Emerging Marine Biotoxins)
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