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Toxins, Volume 7, Issue 8 (August 2015), Pages 2701-3371

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Open AccessArticle Triggering of Erythrocyte Death by Triparanol
Toxins 2015, 7(8), 3359-3371; https://doi.org/10.3390/toxins7083359
Received: 22 July 2015 / Revised: 11 August 2015 / Accepted: 12 August 2015 / Published: 24 August 2015
Cited by 5 | PDF Full-text (586 KB) | HTML Full-text | XML Full-text
Abstract
The cholesterol synthesis inhibitor Triparanol has been shown to trigger apoptosis in several malignancies. Similar to the apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface.
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The cholesterol synthesis inhibitor Triparanol has been shown to trigger apoptosis in several malignancies. Similar to the apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include oxidative stress which may activate erythrocytic Ca2+ permeable unselective cation channels with subsequent Ca2+ entry and increase of cytosolic Ca2+ activity ([Ca2+]i). The present study explored whether and how Triparanol induces eryptosis. To this end, phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fluorescence, and ROS formation from 2’,7’-dichlorodihydrofluorescein diacetate (DCFDA) dependent fluorescence. As a result, a 48 h exposure of human erythrocytes to Triparanol (20 µM) significantly increased DCFDA fluorescence and significantly increased Fluo3-fluorescence. Triparanol (15 µM) significantly increased the percentage of annexin-V-binding cells, and significantly decreased the forward scatter. The effect of Triparanol on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+. In conclusion, Triparanol leads to eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane. Triparanol is at least in part effective by stimulating ROS formation and Ca2+ entry. Full article
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Open AccessArticle Signaling beyond Punching Holes: Modulation of Cellular Responses by Vibrio cholerae Cytolysin
Toxins 2015, 7(8), 3344-3358; https://doi.org/10.3390/toxins7083344
Received: 29 June 2015 / Revised: 12 August 2015 / Accepted: 14 August 2015 / Published: 21 August 2015
Cited by 6 | PDF Full-text (903 KB) | HTML Full-text | XML Full-text
Abstract
Pore-forming toxins (PFTs) are a distinct class of membrane-damaging cytolytic proteins that contribute significantly towards the virulence processes employed by various pathogenic bacteria. Vibrio cholerae cytolysin (VCC) is a prominent member of the beta-barrel PFT (beta-PFT) family. It is secreted by most of
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Pore-forming toxins (PFTs) are a distinct class of membrane-damaging cytolytic proteins that contribute significantly towards the virulence processes employed by various pathogenic bacteria. Vibrio cholerae cytolysin (VCC) is a prominent member of the beta-barrel PFT (beta-PFT) family. It is secreted by most of the pathogenic strains of the intestinal pathogen V. cholerae. Owing to its potent membrane-damaging cell-killing activity, VCC is believed to play critical roles in V. cholerae pathogenesis, particularly in those strains that lack the cholera toxin. Large numbers of studies have explored the mechanistic basis of the cell-killing activity of VCC. Consistent with the beta-PFT mode of action, VCC has been shown to act on the target cells by forming transmembrane oligomeric beta-barrel pores, thereby leading to permeabilization of the target cell membranes. Apart from the pore-formation-induced direct cell-killing action, VCC exhibits the potential to initiate a plethora of signal transduction pathways that may lead to apoptosis, or may act to enhance the cell survival/activation responses, depending on the type of target cells. In this review, we will present a concise view of our current understanding regarding the multiple aspects of these cellular responses, and their underlying signaling mechanisms, evoked by VCC. Full article
(This article belongs to the Special Issue The Cell Biology of Toxins and Effector Proteins from Vibrio cholerae)
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Open AccessArticle Protective Effects of Bacillus subtilis ANSB060 on Serum Biochemistry, Histopathological Changes and Antioxidant Enzyme Activities of Broilers Fed Moldy Peanut Meal Naturally Contaminated with Aflatoxins
Toxins 2015, 7(8), 3330-3343; https://doi.org/10.3390/toxins7083330
Received: 1 July 2015 / Revised: 10 August 2015 / Accepted: 11 August 2015 / Published: 21 August 2015
Cited by 10 | PDF Full-text (1494 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to investigate the toxic effects of aflatoxins and evaluate the effectiveness of Bacillus subtilis ANSB060 in detoxifying aflatoxicosis in broilers. A total of 360 one-week-old male broilers (Ross 308) were assigned to six dietary treatments for five
[...] Read more.
The aim of this study was to investigate the toxic effects of aflatoxins and evaluate the effectiveness of Bacillus subtilis ANSB060 in detoxifying aflatoxicosis in broilers. A total of 360 one-week-old male broilers (Ross 308) were assigned to six dietary treatments for five weeks. The treatment diets were: C0 (basal diet); C1.0 (C0 + 1.0 g B. subtilis ANSB060/kg diet); M0 (basal diet formulated with moldy peanut meal); M0.5, M1.0 and M2.0 (M0 + 0.5, 1.0 and 2.0 g B. subtilis ANSB060/kg diet, respectively). The contents of aflatoxin B1, B2, G1 and G2 in the diets formulated with moldy peanut meal were 70.7 ± 1.3, 11.0 ± 1.5, 6.5 ± 0.8 and 2.0 ± 0.3 µg/kg, respectively. The results showed that aflatoxins increased (p < 0.05) serum aspartate transaminase activity, decreased (p < 0.05) serum glutathione peroxidase activity, and enhanced (p < 0.05) malondialdehyde contents in both the serum and liver. Aflatoxins also caused gross and histological changes in liver tissues, such as bile duct epithelium hyperplasia, vacuolar degeneration and lymphocyte infiltration. The supplementation of ANSB060 reduced aflatoxin levels in the duodenum and counteracted the negative effects of aflatoxins, leading to the conclusion that ANSB060 has a protective effect against aflatoxicosis and this protection is dose-related. Full article
(This article belongs to the collection Understanding Mycotoxin Occurrence in Food and Feed Chains)
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Open AccessArticle Presence of Multiple Mycotoxins and Other Fungal Metabolites in Native Grasses from a Wetland Ecosystem in Argentina Intended for Grazing Cattle
Toxins 2015, 7(8), 3309-3329; https://doi.org/10.3390/toxins7083309
Received: 27 June 2015 / Revised: 12 August 2015 / Accepted: 14 August 2015 / Published: 20 August 2015
Cited by 5 | PDF Full-text (394 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to evaluate the occurrence of several fungal metabolites, including mycotoxins in natural grasses (Poaceae) intended for grazing cattle. A total number of 72 and 77 different metabolites were detected on 106 and 69 grass samples collected during
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The aim of this study was to evaluate the occurrence of several fungal metabolites, including mycotoxins in natural grasses (Poaceae) intended for grazing cattle. A total number of 72 and 77 different metabolites were detected on 106 and 69 grass samples collected during 2011 and 2014, respectively. A total of 60 metabolites were found across both years. Among the few mycotoxins considered toxic for ruminants, no samples of natural grasses were contaminated with aflatoxins, ochratoxin A, ergot alkaloids, and gliotoxin, among others. However, we were able to detect important metabolites (toxic to ruminants) such as type A trichothecenes, mainly T-2 toxin and HT-2 toxin (up to 5000 µg/kg each), and zearalenone (up to 2000 µg/kg), all at very high frequencies and levels. Other fungal metabolites that were found to be prevalent were other Fusarium metabolites like beauvericin, equisetin and aurofusarin, metabolites produced by Alternaria spp., sterigmatocystin and its precursors and anthrachinone derivatives. It is important to point out that the profile of common metabolites was shared during both years of sampling, and also that the occurrence of important metabolites is not a sporadic event. Considering that this area of temperate grassland is used for grazing cattle all year long due to the richness in palatable grasses (Poaceae), the present work represents a starting point for further studies on the occurrence of multi-mycotoxins in natural grasses in order to have a complete picture of the extent of cattle exposure. Also, the present study shows that the presence of zeranol in urine of beef cattle may not be a consequence of illegal use of this banned substance, but the product of the natural occurrence of zearalenone and α-zearalenol in natural grasses intended for cattle feeding. Full article
(This article belongs to the collection Understanding Mycotoxin Occurrence in Food and Feed Chains)
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Open AccessArticle Zearalenone and Its Derivatives α-Zearalenol and β-Zearalenol Decontamination by Saccharomyces cerevisiae Strains Isolated from Bovine Forage
Toxins 2015, 7(8), 3297-3308; https://doi.org/10.3390/toxins7083297
Received: 6 July 2015 / Revised: 4 August 2015 / Accepted: 7 August 2015 / Published: 20 August 2015
Cited by 9 | PDF Full-text (581 KB) | HTML Full-text | XML Full-text
Abstract
Zearalenone (ZEA) and its derivatives are mycotoxins with estrogenic effects on mammals. The biotransformation for ZEA in animals involves the formation of two major metabolites, α- and β-zearalenol (α-ZOL and β-ZOL), which are subsequently conjugated with glucuronic acid. The capability of Saccharomyces cerevisiae
[...] Read more.
Zearalenone (ZEA) and its derivatives are mycotoxins with estrogenic effects on mammals. The biotransformation for ZEA in animals involves the formation of two major metabolites, α- and β-zearalenol (α-ZOL and β-ZOL), which are subsequently conjugated with glucuronic acid. The capability of Saccharomyces cerevisiae strains isolated from silage to eliminate ZEA and its derivatives α-ZOL and β-ZOL was investigated as, also, the mechanisms involved. Strains were grown on Yeast Extract-Peptone-Dextrose medium supplemented with the mycotoxins and their elimination from medium was quantified over time by HPLC-FL. A significant effect on the concentration of ZEA was observed, as all the tested strains were able to eliminate more than 90% of the mycotoxin from the culture medium in two days. The observed elimination was mainly due to ZEA biotransformation into β-ZOL (53%) and α-ZOL (8%) rather than to its adsorption to yeast cells walls. Further, the biotransformation of α-ZOL was not observed but a small amount of β-ZOL (6%) disappeared from culture medium. ZEA biotransformation by yeasts may not be regarded as a full detoxification process because both main end-products are still estrogenic. Nonetheless, it was observed that the biotransformation favors the formation of β-ZOL which is less estrogenic than ZEA and α-ZOL. This metabolic effect is only possible if active strains are used as feed additives and may play a role in the detoxification performance of products with viable S. cerevisiae cells. Full article
(This article belongs to the collection Understanding Mycotoxin Occurrence in Food and Feed Chains)
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Open AccessReview Genetic Factors Involved in Fumonisin Accumulation in Maize Kernels and Their Implications in Maize Agronomic Management and Breeding
Toxins 2015, 7(8), 3267-3296; https://doi.org/10.3390/toxins7083267
Received: 1 June 2015 / Revised: 5 August 2015 / Accepted: 11 August 2015 / Published: 20 August 2015
Cited by 9 | PDF Full-text (542 KB) | HTML Full-text | XML Full-text
Abstract
Contamination of maize with fumonisins depends on the environmental conditions; the maize resistance to contamination and the interaction between both factors. Although the effect of environmental factors is a determinant for establishing the risk of kernel contamination in a region, there is sufficient
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Contamination of maize with fumonisins depends on the environmental conditions; the maize resistance to contamination and the interaction between both factors. Although the effect of environmental factors is a determinant for establishing the risk of kernel contamination in a region, there is sufficient genetic variability among maize to develop resistance to fumonisin contamination and to breed varieties with contamination at safe levels. In addition, ascertaining which environmental factors are the most important in a region will allow the implementation of risk monitoring programs and suitable cultural practices to reduce the impact of such environmental variables. The current paper reviews all works done to address the influence of environmental variables on fumonisin accumulation, the genetics of maize resistance to fumonisin accumulation, and the search for the biochemical and/or structural mechanisms of the maize plant that could be involved in resistance to fumonisin contamination. We also explore the outcomes of breeding programs and risk monitoring of undertaken projects. Full article
(This article belongs to the collection Understanding Mycotoxin Occurrence in Food and Feed Chains)
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Open AccessArticle Extracellular Xylanolytic and Pectinolytic Hydrolase Production by Aspergillus flavus Isolates Contributes to Crop Invasion
Toxins 2015, 7(8), 3257-3266; https://doi.org/10.3390/toxins7083257
Received: 6 July 2015 / Revised: 30 July 2015 / Accepted: 3 August 2015 / Published: 19 August 2015
Cited by 3 | PDF Full-text (450 KB) | HTML Full-text | XML Full-text
Abstract
Several atoxigenic Aspergillus flavus isolates, including some being used as biocontrol agents, and one toxigenic isolate were surveyed for the ability to produce extracellular xylanolytic and pectinolytic hydrolases. All of the tested isolates displayed good production of endoxylanases when grown on a medium
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Several atoxigenic Aspergillus flavus isolates, including some being used as biocontrol agents, and one toxigenic isolate were surveyed for the ability to produce extracellular xylanolytic and pectinolytic hydrolases. All of the tested isolates displayed good production of endoxylanases when grown on a medium utilizing larch xylan as a sole carbon substrate. Four of the tested isolates produced reasonably high levels of esterase activity, while the atoxigenic biocontrol agent NRRL 21882 isolate esterase level was significantly lower than the others. Atoxigenic A. flavus isolates 19, 22, K49, AF36 (the latter two are biocontrol agents) and toxigenic AF13 produced copious levels of pectinolytic activity when grown on a pectin medium. The pectinolytic activity levels of the atoxigenic A. flavus 17 and NRRL 21882 isolates were significantly lower than the other tested isolates. In addition, A. flavus isolates that displayed high levels of pectinolytic activity in the plate assay produced high levels of endopolygalacturonase (pectinase) P2c, as ascertained by isoelectric focusing electrophoresis. Isolate NRRL 21882 displayed low levels of both pectinase P2c and pectin methyl esterase. A. flavus appears capable of producing these hydrolytic enzymes irrespective of aflatoxin production. This ability of atoxigenic isolates to produce xylanolytic and pectinolytic hydrolases mimics that of toxigenic isolates and, therefore, contributes to the ability of atoxigenic isolates to occupy the same niche as A. flavus toxigenic isolates. Full article
(This article belongs to the collection Aflatoxins)
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Open AccessArticle Dendritic Cell Protection from Cisplatin Nephrotoxicity Is Independent of Neutrophils
Toxins 2015, 7(8), 3245-3256; https://doi.org/10.3390/toxins7083245
Received: 8 June 2015 / Revised: 11 August 2015 / Accepted: 12 August 2015 / Published: 19 August 2015
Cited by 7 | PDF Full-text (2030 KB) | HTML Full-text | XML Full-text
Abstract
Cisplatin is a very effective chemotherapeutic agent used against a wide range of solid tumors. A major adverse effect of cisplatin therapy is acute kidney injury (AKI). Neutrophils are reported to infiltrate and exacerbate injury in a wide range of sterile inflammatory models
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Cisplatin is a very effective chemotherapeutic agent used against a wide range of solid tumors. A major adverse effect of cisplatin therapy is acute kidney injury (AKI). Neutrophils are reported to infiltrate and exacerbate injury in a wide range of sterile inflammatory models of tissue injury. Here, we studied the kinetics of neutrophil infiltration into kidneys and their role in cisplatin-mediated AKI. Mice treated with cisplatin showed an increase in circulating neutrophils 24 and 48 h after cisplatin administration. Cisplatin treatment caused an increase in kidney leukocytes with neutrophils accounting for the majority of the infiltrating leukocytes. The extent of neutrophil infiltration coincided with the severity of kidney injury and renal dysfunction. To examine the functional relevance of infiltrating neutrophils in cisplatin nephrotoxicity, we depleted neutrophils using a neutrophil-specific antibody (anti-Ly-6G). This antibody resulted in greater than 90% depletion of neutrophils in both the blood and kidney. Of note, depletion of neutrophils had no impact on the extent of cisplatin-induced AKI as compared to non-depleted mice. Earlier, we reported that dendritic cell depletion in CD11c-DTRtg mice causes exacerbation of AKI and a dramatic increase in renal neutrophils. Thus, we also examined the role of neutrophils in dendritic cell-depleted mice treated with cisplatin. Dendritic cell depletion exacerbated AKI in spite of neutrophil depletion. These data demonstrate that cisplatin nephrotoxicity is not mediated by neutrophils and that dendritic cells protect kidneys via neutrophil-independent mechanisms. Full article
(This article belongs to the collection Toxicity and Therapeutic Interventions in the Immune System)
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Open AccessArticle Spatiotemporal Dynamics of Microcystin Variants and Relationships with Environmental Parameters in Lake Taihu, China
Toxins 2015, 7(8), 3224-3244; https://doi.org/10.3390/toxins7083224
Received: 10 June 2015 / Revised: 5 August 2015 / Accepted: 11 August 2015 / Published: 18 August 2015
Cited by 14 | PDF Full-text (1517 KB) | HTML Full-text | XML Full-text
Abstract
Excessive anthropogenically-caused nutrient loading from both external and internal sources has promoted the growth of cyanobacteria in Lake Taihu from 2005 to 2014, suggesting increased production and release of cyanotoxins. In order to explain the spatial distribution and temporal variation of microcystins (MCs),
[...] Read more.
Excessive anthropogenically-caused nutrient loading from both external and internal sources has promoted the growth of cyanobacteria in Lake Taihu from 2005 to 2014, suggesting increased production and release of cyanotoxins. In order to explain the spatial distribution and temporal variation of microcystins (MCs), the intracellular concentrations of MCs (MC-LR, -RR and -YR, L, R and Y are abbreviations of leucine, arginine and tyrosine) were monitored monthly from July 2013 to June 2014. Three MC variants are present simultaneously in Lake Taihu; the MC-LR and -RR variants were dominant (accounting for 40% and 39% of the total), followed by MC-YR (21%). However, MC-YR accounted for a higher proportion in colder months, especially in March. The highest concentrations of intracellular MCs were found in July and October when cyanobacteria cell density also reached the maximum. The average concentrations of MC-LR, -RR and -YR in July were 4.69, 4.23 and 2.01 μg/L, respectively. In terms of the entire lake, toxin concentrations in northern parts were significantly higher than the eastern part in summer, when MC concentrations were several times higher than the guideline value by WHO throughout much of Lake Taihu. Results from correlation and redundancy analysis (RDA) showed that total MCs, including all variants, were strongly and positively correlated with cyanobacteria cell density, water temperature, total phosphorus (TP) and pH, whereas each variant had different correlation coefficients with each of the considered environmental variables. MC-RR showed a stronger relationship with temperature, in contrast to MC-YR and -LR. Dissolved inorganic carbon (DIC) showed a negative relationship with each variant, suggesting that rising DIC concentrations may inhibit cyanobacterial growth and thereby reduce MC production in the future. Full article
(This article belongs to the Section Marine and Freshwater Toxins)
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Open AccessArticle Zearalenone in the Intestinal Tissues of Immature Gilts Exposed per os to Mycotoxins
Toxins 2015, 7(8), 3210-3223; https://doi.org/10.3390/toxins7083210
Received: 16 April 2015 / Revised: 31 July 2015 / Accepted: 11 August 2015 / Published: 18 August 2015
Cited by 11 | PDF Full-text (256 KB) | HTML Full-text | XML Full-text
Abstract
Zearalenone and its metabolites, α-zearalenol and β-zearalenol, demonstrate estradiol-like activity and disrupt physiological functions in animals. This article evaluates the carryover of zearalenone and its selected metabolites from the digesta to intestinal walls (along the entire intestines) in pre-pubertal gilts exposed to low
[...] Read more.
Zearalenone and its metabolites, α-zearalenol and β-zearalenol, demonstrate estradiol-like activity and disrupt physiological functions in animals. This article evaluates the carryover of zearalenone and its selected metabolites from the digesta to intestinal walls (along the entire intestines) in pre-pubertal gilts exposed to low doses of zearalenone over long periods of time. The term “carryover” describes the transfer of mycotoxins from feed to edible tissues, and it was used to assess the risk of mycotoxin exposure for consumers. The experimental gilts with body weight of up to 25 kg were per os administered zearalenone at a daily dose of 40 μg/kg BW (Group E, n = 18) or placebo (Group C, n = 21) over a period of 42 days. In the first weeks of exposure, the highest values of the carryover factor were noted in the duodenum and the jejunum. In animals receiving pure zearalenone, the presence of metabolites was not determined in intestinal tissues. In the last three weeks of the experiment, very high values of the carryover factor were observed in the duodenum and the descending colon. The results of the study indicate that in animals exposed to subclinical doses of zearalenone, the carryover factor could be determined by the distribution and expression of estrogen receptor beta. Full article
(This article belongs to the collection Fusarium Toxins – Relevance for Human and Animal Health)
Open AccessReview Pharmacological Alternatives for the Treatment of Neurodegenerative Disorders: Wasp and Bee Venoms and Their Components as New Neuroactive Tools
Toxins 2015, 7(8), 3179-3209; https://doi.org/10.3390/toxins7083179
Received: 15 May 2015 / Revised: 1 August 2015 / Accepted: 5 August 2015 / Published: 18 August 2015
Cited by 11 | PDF Full-text (835 KB) | HTML Full-text | XML Full-text
Abstract
Neurodegenerative diseases are relentlessly progressive, severely impacting affected patients, families and society as a whole. Increased life expectancy has made these diseases more common worldwide. Unfortunately, available drugs have insufficient therapeutic effects on many subtypes of these intractable diseases, and adverse effects hamper
[...] Read more.
Neurodegenerative diseases are relentlessly progressive, severely impacting affected patients, families and society as a whole. Increased life expectancy has made these diseases more common worldwide. Unfortunately, available drugs have insufficient therapeutic effects on many subtypes of these intractable diseases, and adverse effects hamper continued treatment. Wasp and bee venoms and their components are potential means of managing or reducing these effects and provide new alternatives for the control of neurodegenerative diseases. These venoms and their components are well-known and irrefutable sources of neuroprotectors or neuromodulators. In this respect, the present study reviews our current understanding of the mechanisms of action and future prospects regarding the use of new drugs derived from wasp and bee venom in the treatment of major neurodegenerative disorders, including Alzheimer’s Disease, Parkinson’s Disease, Epilepsy, Multiple Sclerosis and Amyotrophic Lateral Sclerosis. Full article
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Open AccessReview Anthrax Toxins in Context of Bacillus anthracis Spores and Spore Germination
Toxins 2015, 7(8), 3167-3178; https://doi.org/10.3390/toxins7083167
Received: 29 July 2015 / Revised: 8 August 2015 / Accepted: 11 August 2015 / Published: 17 August 2015
Cited by 4 | PDF Full-text (387 KB) | HTML Full-text | XML Full-text
Abstract
The interaction of anthrax toxin or toxin components with B. anthracis spores has been demonstrated. Germinating spores can produce significant amounts of toxin components very soon after the initiation of germination. In this review, we will summarize the work performed that has led
[...] Read more.
The interaction of anthrax toxin or toxin components with B. anthracis spores has been demonstrated. Germinating spores can produce significant amounts of toxin components very soon after the initiation of germination. In this review, we will summarize the work performed that has led to our understanding of toxin and spore interactions and discuss the complexities associated with these interactions Full article
(This article belongs to the collection Anthrax Toxins)
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Open AccessArticle Increased Proinflammatory Cytokine Production and Decreased Cholesterol Efflux Due to Downregulation of ABCG1 in Macrophages Exposed to Indoxyl Sulfate
Toxins 2015, 7(8), 3155-3166; https://doi.org/10.3390/toxins7083155
Received: 6 July 2015 / Revised: 31 July 2015 / Accepted: 6 August 2015 / Published: 14 August 2015
Cited by 4 | PDF Full-text (708 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
One of the possible causes of enhanced atherosclerosis in patients with chronic kidney disease (CKD) is the accumulation of uremic toxins. Since macrophage foam cell formation is a hallmark of atherosclerosis, we examined the direct effect of indoxyl sulfate (IS), a representative uremic
[...] Read more.
One of the possible causes of enhanced atherosclerosis in patients with chronic kidney disease (CKD) is the accumulation of uremic toxins. Since macrophage foam cell formation is a hallmark of atherosclerosis, we examined the direct effect of indoxyl sulfate (IS), a representative uremic toxin, on macrophage function. Macrophages differentiated from THP-1 cells were exposed to IS in vitro. IS decreased the cell viability of THP-1 derived macrophages but promoted the production of inflammatory cytokines (IL-1β, IS 1.0 mM: 101.8 ± 21.8 pg/mL vs. 0 mM: 7.0 ± 0.3 pg/mL, TNF-α, IS 1.0 mM: 96.6 ± 11.0 pg/mL vs. 0 mM: 15.1 ± 3.1 pg/mL) and reactive oxygen species. IS reduced macrophage cholesterol efflux (IS 0.5 mM: 30.3% ± 7.3% vs. 0 mM: 43.5% ± 1.6%) and decreased ATP-binding cassette transporter G1 expression. However, lipid uptake into cells was not enhanced. A liver X receptor (LXR) agonist, T0901317, improved IS-induced production of inflammatory cytokines as well as reduced cholesterol efflux. In conclusion, IS induced inflammatory reactions and reduced cholesterol efflux in macrophages. Both effects of IS were improved with activation of LXR. Direct interactions of uremic toxins with macrophages may be a major cause of atherosclerosis acceleration in patients with CKD. Full article
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Open AccessReview Botulinum Toxin for Neuropathic Pain: A Review of the Literature
Toxins 2015, 7(8), 3127-3154; https://doi.org/10.3390/toxins7083127
Received: 27 June 2015 / Revised: 29 July 2015 / Accepted: 7 August 2015 / Published: 14 August 2015
Cited by 29 | PDF Full-text (670 KB) | HTML Full-text | XML Full-text
Abstract
Botulinum neurotoxin (BoNT), derived from Clostridium botulinum, has been used therapeutically for focal dystonia, spasticity, and chronic migraine. Its spectrum as a potential treatment for neuropathic pain has grown. Recent opinions on the mechanism behind the antinociceptive effects of BoNT suggest that
[...] Read more.
Botulinum neurotoxin (BoNT), derived from Clostridium botulinum, has been used therapeutically for focal dystonia, spasticity, and chronic migraine. Its spectrum as a potential treatment for neuropathic pain has grown. Recent opinions on the mechanism behind the antinociceptive effects of BoNT suggest that it inhibits the release of peripheral neurotransmitters and inflammatory mediators from sensory nerves. There is some evidence showing the axonal transport of BoNT, but it remains controversial. The aim of this review is to summarize the experimental and clinical evidence of the antinociceptive effects, mechanisms, and therapeutic applications of BoNT for neuropathic pain conditions, including postherpetic neuralgia, complex regional pain syndrome, and trigeminal neuralgia. The PubMed and OvidSP databases were searched from 1966 to May 2015. We assessed levels of evidence according to the American Academy of Neurology guidelines. Recent studies have suggested that BoNT injection is an effective treatment for postherpetic neuralgia and is likely efficient for trigeminal neuralgia and post-traumatic neuralgia. BoNT could also be effective as a treatment for diabetic neuropathy. It has not been proven to be an effective treatment for occipital neuralgia or complex regional pain syndrome. Full article
(This article belongs to the collection Botulinum Toxins on Human Pain)
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Open AccessArticle The Metabolic Fate of Deoxynivalenol and Its Acetylated Derivatives in a Wheat Suspension Culture: Identification and Detection of DON-15-O-Glucoside, 15-Acetyl-DON-3-O-Glucoside and 15-Acetyl-DON-3-Sulfate
Toxins 2015, 7(8), 3112-3126; https://doi.org/10.3390/toxins7083112
Received: 24 June 2015 / Revised: 24 July 2015 / Accepted: 4 August 2015 / Published: 12 August 2015
Cited by 16 | PDF Full-text (1433 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Deoxynivalenol (DON) is a protein synthesis inhibitor produced by the Fusarium species, which frequently contaminates grains used for human or animal consumption. We treated a wheat suspension culture with DON or one of its acetylated derivatives, 3-acetyl-DON (3-ADON), 15-acetyl-DON (15-ADON) and 3,15-diacetyl-DON (3,15-diADON),
[...] Read more.
Deoxynivalenol (DON) is a protein synthesis inhibitor produced by the Fusarium species, which frequently contaminates grains used for human or animal consumption. We treated a wheat suspension culture with DON or one of its acetylated derivatives, 3-acetyl-DON (3-ADON), 15-acetyl-DON (15-ADON) and 3,15-diacetyl-DON (3,15-diADON), and monitored the metabolization over a course of 96 h. Supernatant and cell extract samples were analyzed using a tailored LC-MS/MS method for the quantification of DON metabolites. We report the formation of tentatively identified DON-15-O-β-D-glucoside (D15G) and of 15-acetyl-DON-3-sulfate (15-ADON3S) as novel deoxynivalenol metabolites in wheat. Furthermore, we found that the recently identified 15-acetyl-DON-3-O-β-D-glucoside (15-ADON3G) is the major metabolite produced after 15-ADON challenge. 3-ADON treatment led to a higher intracellular content of toxic metabolites after six hours compared to all other treatments. 3-ADON was exclusively metabolized into DON before phase II reactions occurred. In contrast, we found that 15-ADON was directly converted into 15-ADON3G and 15-ADON3S in addition to metabolization into deoxynivalenol-3-O-β-D-glucoside (D3G). This study highlights significant differences in the metabolization of DON and its acetylated derivatives. Full article
(This article belongs to the Section Mycotoxins)
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