Toxins

11 pages, 851 KiB

Open AccessArticle

Palmatine from Unexplored Rutidea parviflora Showed Cytotoxicity and Induction of Apoptosis in Human Ovarian Cancer Cells

by Okiemute Rosa Johnson-Ajinwo, Alan Richardson and Wen-Wu Li

Toxins 2019, 11(4), 237; https://doi.org/10.3390/toxins11040237 - 25 Apr 2019

Cited by 12 | Viewed by 4445

Abstract

Ovarian cancer ranks amongst the deadliest cancers in the gynaecological category of cancers. This research work aims to evaluate in vitro anti-ovarian cancer activities and identify phytochemical constituents of a rarely explored plant species—Rutidea parviflora DC. The aqueous and organic extracts of [...] Read more.

Ovarian cancer ranks amongst the deadliest cancers in the gynaecological category of cancers. This research work aims to evaluate in vitro anti-ovarian cancer activities and identify phytochemical constituents of a rarely explored plant species—Rutidea parviflora DC. The aqueous and organic extracts of the plant were evaluated for cytotoxicity using sulforhodamine B assay in four ovarian cancer cell lines and an immortalized human ovarian epithelial (HOE) cell line. The bioactive compounds were isolated and characterized by gas/liquid chromatography mass spectrometry and nuclear magnetic resonance spectroscopy. Caspase 3/7 activity assay, western blotting and flow cytometry were carried out to assess apoptotic effects of active compounds. The extracts/fractions of R. parviflora showed promising anti-ovarian cancer activities in ovarian cancer cell lines. A principal cytotoxic alkaloid was identified as palmatine whose IC₅₀ was determined as 5.5–7.9 µM. Palmatine was relatively selective towards cancer cells as it was less cytotoxic toward HOE cells, also demonstrating interestingly absence of cross-resistance in cisplatin-resistant A2780 cells. Palmatine further induced apoptosis by increasing caspase 3/7 activity, poly-ADP-ribose polymerase cleavage, and annexin V and propidium iodide staining in OVCAR-4 cancer cells. Our studies warranted further investigation of palmatine and R. parviflora extracts in preclinical models of ovarian cancer. Full article

(This article belongs to the Special Issue Biological Activities of Alkaloids: From Toxicology to Pharmacology)

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11 pages, 2092 KiB

Open AccessArticle

Isolation and Characterization of Insecticidal Toxins from the Venom of the North African Scorpion, Buthacus leptochelys

by Yusuke Yoshimoto, Masahiro Miyashita, Mohammed Abdel-Wahab, Moustafa Sarhan, Yoshiaki Nakagawa and Hisashi Miyagawa

Toxins 2019, 11(4), 236; https://doi.org/10.3390/toxins11040236 - 25 Apr 2019

Cited by 9 | Viewed by 4888

Abstract

Various bioactive peptides have been identified in scorpion venom, but there are many scorpion species whose venom has not been investigated. In this study, we characterized venom components of the North African scorpion, Buthacus leptochelys, by mass spectrometric analysis and evaluated their [...] Read more.

Various bioactive peptides have been identified in scorpion venom, but there are many scorpion species whose venom has not been investigated. In this study, we characterized venom components of the North African scorpion, Buthacus leptochelys, by mass spectrometric analysis and evaluated their insect toxicity. This is the first report of chemical and biological characterization of the B. leptochelys venom. LC/MS analysis detected at least 148 components in the venom. We isolated four peptides that show insect toxicity (Bl-1, Bl-2, Bl-3, and Bl-4) through bioassay-guided HPLC fractionation. These toxins were found to be similar to scorpion α- and β-toxins based on their N-terminal sequences. Among them, the complete primary structure of Bl-1 was determined by combination of Edman degradation and MS/MS analysis. Bl-1 is composed of 67 amino acid residues and crosslinked with four disulfide bonds. Since Bl-1 shares high sequence similarity with α-like toxins, it is likely that it acts on Na⁺ channels of both insects and mammals. Full article

(This article belongs to the Special Issue Arthropod Venom Components and Their Potential Usage)

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15 pages, 828 KiB

Open AccessEditor’s ChoiceArticle

Uremic Toxin Concentrations are Related to Residual Kidney Function in the Pediatric Hemodialysis Population

by Evelien Snauwaert, Els Holvoet, Wim Van Biesen, Ann Raes, Griet Glorieux, Johan Vande Walle, Sanne Roels, Raymond Vanholder, Varvara Askiti, Karolis Azukaitis, Aysun Bayazit, Nur Canpolat, Michel Fischbach, Nathalie Godefroid, Saoussen Krid, Mieczyslaw Litwin, Lukasz Obrycki, Fabio Paglialonga, Bruno Ranchin, Charlotte Samaille, Franz Schaefer, Claus Peter Schmitt, Brankica Spasojevic, Constantinos J. Stefanidis, Maria Van Dyck, Koen Van Hoeck, Laure Collard, Sunny Eloot and Rukshana Shroff Show full author list Hide full author list

Toxins 2019, 11(4), 235; https://doi.org/10.3390/toxins11040235 - 24 Apr 2019

Cited by 22 | Viewed by 4122

Abstract

Protein-bound uremic toxins (PBUTs) play a role in the multisystem disease that children on hemodialysis (HD) are facing, but little is known about their levels and protein binding (%PB). In this study, we evaluated the levels and %PB of six PBUTs cross-sectionally in [...] Read more.

Protein-bound uremic toxins (PBUTs) play a role in the multisystem disease that children on hemodialysis (HD) are facing, but little is known about their levels and protein binding (%PB). In this study, we evaluated the levels and %PB of six PBUTs cross-sectionally in a large pediatric HD cohort (n = 170) by comparing these with healthy and non-dialysis chronic kidney disease (CKD) stage 4–5 (n = 24) children. In parallel β2-microglobulin (β2M) and uric acid (UA) were evaluated. We then explored the impact of age and residual kidney function on uremic toxin levels and %PB using analysis of covariance and Spearman correlation coefficients (r_s). We found higher levels of β2M, p-cresyl glucuronide (pCG), hippuric acid (HA), indole acetic acid (IAA), and indoxyl sulfate (IxS) in the HD compared to the CKD4–5 group. In the HD group, a positive correlation between age and pCG, HA, IxS, and pCS levels was shown. Residual urine volume was negatively correlated with levels of β2M, pCG, HA, IAA, IxS, and CMPF (r_s −0.2 to −0.5). In addition, we found overall lower %PB of PBUTs in HD versus the CKD4–5 group, and showed an age-dependent increase in %PB of IAA, IxS, and pCS. Furhtermore, residual kidney function was overall positively correlated with %PB of PBUTs. In conclusion, residual kidney function and age contribute to PBUT levels and %PB in the pediatric HD population. Full article

(This article belongs to the Special Issue Disposition of Uremic Toxins: The Challenges in Uremia)

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9 pages, 741 KiB

Open AccessEditor’s ChoiceArticle

Antiparasitic Properties of Cantharidin and the Blister Beetle Berberomeloe majalis (Coleoptera: Meloidae)

by Douglas W. Whitman, Maria Fe Andrés, Rafael A. Martínez-Díaz, Alexandra Ibáñez-Escribano, A. Sonia Olmeda and Azucena González-Coloma

Toxins 2019, 11(4), 234; https://doi.org/10.3390/toxins11040234 - 22 Apr 2019

Cited by 21 | Viewed by 8305

Abstract

Cantharidin (CTD) is a toxic monoterpene produced by blister beetles (Fam. Meloidae) as a chemical defense against predators. Although CTD is highly poisonous to many predator species, some have evolved the ability to feed on poisonous Meloidae, or otherwise beneficially use blister beetles. [...] Read more.

Cantharidin (CTD) is a toxic monoterpene produced by blister beetles (Fam. Meloidae) as a chemical defense against predators. Although CTD is highly poisonous to many predator species, some have evolved the ability to feed on poisonous Meloidae, or otherwise beneficially use blister beetles. Great Bustards, Otis tarda, eat CTD-containing Berberomeloe majalis blister beetles, and it has been hypothesized that beetle consumption by these birds reduces parasite load (a case of self-medication). We examined this hypothesis by testing diverse organisms against CTD and extracts of B. majalis hemolymph and bodies. Our results show that all three preparations (CTD and extracts of B. majalis) were toxic to a protozoan (Trichomonas vaginalis), a nematode (Meloidogyne javanica), two insects (Myzus persicae and Rhopalosiphum padi) and a tick (Hyalomma lusitanicum). This not only supports the anti-parasitic hypothesis for beetle consumption, but suggests potential new roles for CTD, under certain conditions. Full article

(This article belongs to the Special Issue Arthropod Venom Components and Their Potential Usage)

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15 pages, 5100 KiB

Open AccessEditor’s ChoiceArticle

Structural Insights to the Heterotetrameric Interaction between the Vibrio parahaemolyticus PirA^vp and PirB^vp Toxins and Activation of the Cry-Like Pore-Forming Domain

by Shin-Jen Lin, Yi-Fan Chen, Kai-Cheng Hsu, Yun-Ling Chen, Tzu-Ping Ko, Chu-Fang Lo, Han-Ching Wang and Hao-Ching Wang

Toxins 2019, 11(4), 233; https://doi.org/10.3390/toxins11040233 - 22 Apr 2019

Cited by 30 | Viewed by 5674

Abstract

Acute hepatopancreatic necrosis disease (AHPND) is a newly emergent penaeid shrimp disease which can cause 70–100% mortality in Penaeus vannamei and Penaeus monodon, and has resulted in enormous economic losses since its appearance. AHPND is caused by the specific strains of Vibrio [...] Read more.

Acute hepatopancreatic necrosis disease (AHPND) is a newly emergent penaeid shrimp disease which can cause 70–100% mortality in Penaeus vannamei and Penaeus monodon, and has resulted in enormous economic losses since its appearance. AHPND is caused by the specific strains of Vibrio parahaemolyticus that harbor the pVA1 plasmid and express PirA^vp and PirB^vp toxins. These two toxins have been reported to form a binary complex. When both are present, they lead to the death of shrimp epithelial cells in the hepatopancreas and cause the typical histological symptoms of AHPND. However, the binding mode of PirA^vp and PirB^vp has not yet been determined. Here, we used isothermal titration calorimetry (ITC) to measure the binding affinity of PirA^vp and PirB^vp. Since the dissociation constant (K_d = 7.33 ± 1.20 μM) was considered too low to form a sufficiently stable complex for X-ray crystallographic analysis, we used alternative methods to investigate PirA^vp-PirB^vp interaction, first by using gel filtration to evaluate the molecular weight of the PirA^vp/PirB^vp complex, and then by using cross-linking and hydrogen-deuterium exchange (HDX) mass spectrometry to further understand the interaction interface between PirA^vp and PirB^vp. Based on these results, we propose a heterotetrameric interaction model of this binary toxin complex. This model provides insight of how conformational changes might activate the PirB^vp N-terminal pore-forming domain and should be helpful for devising effective anti-AHPND strategies in the future. Full article

(This article belongs to the Special Issue Pore-Forming Toxins (PFTs): Never Out of Fashion)

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11 pages, 9740 KiB

Open AccessArticle

Clostridium perfringens Delta-Toxin Damages the Mouse Small Intestine

by Soshi Seike, Masaya Takehara, Keiko Kobayashi and Masahiro Nagahama

Toxins 2019, 11(4), 232; https://doi.org/10.3390/toxins11040232 - 22 Apr 2019

Cited by 12 | Viewed by 4165

Abstract

Clostridium perfringens strains B and C cause fatal intestinal diseases in animals. The secreted pore-forming toxin delta-toxin is one of the virulence factors of the strains, but the mechanism of intestinal pathogenesis is unclear. Here, we investigated the effects of delta-toxin on the [...] Read more.

Clostridium perfringens strains B and C cause fatal intestinal diseases in animals. The secreted pore-forming toxin delta-toxin is one of the virulence factors of the strains, but the mechanism of intestinal pathogenesis is unclear. Here, we investigated the effects of delta-toxin on the mouse ileal loop. Delta-toxin caused fluid accumulation and intestinal permeability to fluorescein isothiocyanate (FITC)-dextran in the mouse ileal loop in a dose- and time-dependent manner. Treatment with delta-toxin induced significant histological damage and shortening of villi. Delta-toxin activates a disintegrin and metalloprotease (ADAM) 10, leading to the cleavage of E-cadherin, the epithelial adherens junction protein, in human intestinal epithelial Caco-2 cells. In this study, E-cadherin immunostaining in mouse intestinal epithelial cells was almost undetectable 1 h after toxin treatment. ADAM10 inhibitor (GI254023X) blocked the toxin-induced fluid accumulation and E-cadherin loss in the mouse ileal loop. Delta-toxin stimulated the shedding of intestinal epithelial cells. The shedding cells showed the accumulation of E-cadherin in intracellular vesicles and the increased expression of active caspase-3. Our findings demonstrate that delta-toxin causes intestinal epithelial cell damage through the loss of E-cadherin cleaved by ADAM10. Full article

(This article belongs to the Collection Clostridium difficile/Clostridium sordellii and Clostridium perfringens Toxins)

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14 pages, 1767 KiB

Open AccessArticle

CesH Represses Cereulide Synthesis as an Alpha/Beta Fold Hydrolase in Bacillus cereus

by Shen Tian, Hairong Xiong, Peiling Geng, Zhiming Yuan and Xiaomin Hu

Toxins 2019, 11(4), 231; https://doi.org/10.3390/toxins11040231 - 21 Apr 2019

Cited by 9 | Viewed by 4272

Abstract

Cereulide is notorious as a heat-stable emetic toxin produced by Bacillus cereus and glucose is supposed to be an ingredient supporting its formation. This study showed that glucose addition benefited on cell growth and the early transcription of genes involved in substrate accumulation [...] Read more.

Cereulide is notorious as a heat-stable emetic toxin produced by Bacillus cereus and glucose is supposed to be an ingredient supporting its formation. This study showed that glucose addition benefited on cell growth and the early transcription of genes involved in substrate accumulation and toxin synthesis, but it played a negative role in the final production of cereulide. Meanwhile, a lasting enhancement of cesH transcription was observed with the addition of glucose. Moreover, the cereulide production in ΔcesH was obviously higher than that in the wild type. This indicates that CesH has a repression effect on cereulide production. Bioinformatics analysis revealed that CesH was an alpha/beta hydrolase that probably associated with the cell membrane, which was verified by subcellular localization. The esterase activity against para-nitrophenyl acetate (PNPC2) of the recombinant CesH was confirmed. Although no sign of ester bond cleavage in cereulide or valinomycin was demonstrated in in vitro assays, CesH could reverse the cereulide analogue sensitivity of Bacillus subtilis in vivo, by which toxin degradation was facilitated. Moreover, site directed mutations identified that the conserved catalytic triad of CesH might consist of Serine 86, Glutamate 199, and Histidine 227. These results help us to understand the regulation of cereulide production and provide clues for developing control measurements. Full article

(This article belongs to the Special Issue ADP-Ribosylating Toxin)

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18 pages, 2545 KiB

Open AccessEditor’s ChoiceArticle

A Complete Survey of Glycoalkaloids Using LC-FTICR-MS and IRMPD in a Commercial Variety and a Local Landrace of Eggplant (Solanum melongena L.) and their Anticholinesterase and Antioxidant Activities

by Filomena Lelario, Susanna De Maria, Anna Rita Rivelli, Daniela Russo, Luigi Milella, Sabino Aurelio Bufo and Laura Scrano

Toxins 2019, 11(4), 230; https://doi.org/10.3390/toxins11040230 - 19 Apr 2019

Cited by 35 | Viewed by 6569

Abstract

Eggplant contains glycoalkaloids (GAs), a class of nitrogen-containing secondary metabolites of great structural variety that may have both adverse and beneficial biological effects. In this study, we performed a complete survey of GAs and their malonylated form, in two genotypes of eggplants: A [...] Read more.

Eggplant contains glycoalkaloids (GAs), a class of nitrogen-containing secondary metabolites of great structural variety that may have both adverse and beneficial biological effects. In this study, we performed a complete survey of GAs and their malonylated form, in two genotypes of eggplants: A commercial cultivated type, Mirabella (Mir), with purple peel and bitter taste and a local landrace, named Melanzana Bianca di Senise (Sen), characterized by white peel with purple strip and a typical sweet aroma. Besides the analysis of their morphological traits, nineteen glycoalkaloids were tentatively identified in eggplant berry extracts based upon LC-ESI-FTICR-MS analysis using retention times, elution orders, high-resolution mass spectra, as well as high-resolution fragmentation by IRMPD. The relative signal intensities (i.e., ion counts) of the GAs identified in Mir and Sen pulp extracts showed as solamargine, and its isomers are the most abundant. In addition, anticholinesterase and antioxidant activities of the extracts were evaluated. Pulp tissue was found to be more active in inhibiting acetylcholinesterase enzyme than peel showing an inhibitory effect higher than 20% for Mir pulp. The identification of new malonylated GAs in eggplant is proposed. Full article

(This article belongs to the Special Issue Biological Activities of Alkaloids: From Toxicology to Pharmacology)

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14 pages, 2686 KiB

Open AccessEditor’s ChoiceArticle

Dehydrocrenatidine Inhibits Voltage-Gated Sodium Channels and Ameliorates Mechanic Allodia in a Rat Model of Neuropathic Pain

by Fang Zhao, Qinglian Tang, Jian Xu, Shuangyan Wang, Shaoheng Li, Xiaohan Zou and Zhengyu Cao

Toxins 2019, 11(4), 229; https://doi.org/10.3390/toxins11040229 - 18 Apr 2019

Cited by 15 | Viewed by 4077

Abstract

Picrasma quassioides (D. Don) Benn, a medical plant, is used in clinic to treat inflammation, pain, sore throat, and eczema. The alkaloids are the main active components in P. quassioides. In this study, we examined the analgesic effect of dehydrocrenatidine (DHCT), a [...] Read more.

Picrasma quassioides (D. Don) Benn, a medical plant, is used in clinic to treat inflammation, pain, sore throat, and eczema. The alkaloids are the main active components in P. quassioides. In this study, we examined the analgesic effect of dehydrocrenatidine (DHCT), a β-carboline alkaloid abundantly found in P. quassioides in a neuropathic pain rat model of a sciatic nerve chronic constriction injury. DHCT dose-dependently attenuated the mechanic allodynia. In acutely isolated dorsal root ganglion, DHCT completely suppressed the action potential firing. Further electrophysiological characterization demonstrated that DHCT suppressed both tetrodotoxin-resistant (TTX-R) and sensitive (TTX-S) voltage-gated sodium channel (VGSC) currents with IC₅₀ values of 12.36 μM and 4.87 µM, respectively. DHCT shifted half-maximal voltage (V_1/2) of inactivation to hyperpolarizing direction by ~16.7 mV in TTX-S VGSCs. In TTX-R VGSCs, DHCT shifted V_1/2 of inactivation voltage to hyperpolarizing direction and V_1/2 of activation voltage to more depolarizing potential by ~23.9 mV and ~12.2 mV, respectively. DHCT preferred to interact with an inactivated state of VGSCs and prolonged the repriming time in both TTX-S and TTX-R VGSCs, transiting the channels into a slow inactivated state from a fast inactivated state. Considered together, these data demonstrated that the analgesic effect of DHCT was likely though the inhibition of neuronal excitability. Full article

(This article belongs to the Special Issue Biological Activities of Alkaloids: From Toxicology to Pharmacology)

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20 pages, 1440 KiB

Open AccessArticle

Evaluation of Cytotoxicity and Mould Contamination of Selected Plants from Meadows Covered by the Agri-Environmental Program

by Magdalena Twarużek, Romuald Dembek, Dariusz Pańka, Ewelina Soszczyńska, Ewa Zastempowska and Jan Grajewski

Toxins 2019, 11(4), 228; https://doi.org/10.3390/toxins11040228 - 17 Apr 2019

Cited by 2 | Viewed by 3288

Abstract

The aim of the study was the evaluation of selected species of meadow plants obtained from the first cut from the area covered by the agri-environmental program ‘Natura 2000’ in terms of the presence of cytotoxic compounds detected by the MTT test and [...] Read more.

The aim of the study was the evaluation of selected species of meadow plants obtained from the first cut from the area covered by the agri-environmental program ‘Natura 2000’ in terms of the presence of cytotoxic compounds detected by the MTT test and the level of fungal contamination. The research was carried out on plant species that were evaluated differently in previously used methods for quality assessment of pasture feeds according to Klapp and Filipek. Twenty-six plant species were harvested in 2014 from meadows located in the valley of the Bydgoszcz Canal. Mycological examination of meadow plant samples was carried out according to PN-ISO 7954:1999. Cytotoxicity evaluation was performed using the MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test. Selected samples were also subjected to evaluation of the endophytes occurrence in grasses using PCR. Natural meadow positions included in the study were dominated by moulds belonging to Humicola spp., Alternaria spp., Cladosporium spp., Torula spp., Fusarium spp. and Mucor spp. The highest level of fungal contamination was observed for Carex acutiformis Ehrh. The most infested grasses were Deschampsia caespitosa (L.) P.Beauv., Festuca arundinacea Schreb. and Lolium perenne L. The MTT test showed that the most cytotoxic species were Arrhenatherum elatius (L.) P.Beauv. (IC₅₀ 1.563 mg/mL) and Ranunculus repens L. (IC₅₀ 3.125 mg/mL). Epichloë endophytes were detected in one of 13 examined grass samples. Our own research suggests that previously used feed quality assessments should be verified by introducing modern methods of molecular biology and instrumental analysis. Results of this study may broaden the knowledge of the causes of problems resulting from feeding of roughage, mainly from natural meadows, and help in creating new rankings of the feed value of meadow sward components. Full article

(This article belongs to the Special Issue Fungal Infestations in Humans, Animals, Crops)

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27 pages, 1034 KiB

Open AccessEditor’s ChoiceReview

Mycotoxins during the Processes of Nixtamalization and Tortilla Production

by Sara Schaarschmidt and Carsten Fauhl-Hassek

Toxins 2019, 11(4), 227; https://doi.org/10.3390/toxins11040227 - 16 Apr 2019

Cited by 45 | Viewed by 7890

Abstract

Tortillas are a traditional staple food in Mesoamerican cuisine, which have also become popular on a global level, e.g., for wraps or as snacks (tortilla chips). Traditional tortilla production includes alkaline cooking (nixtamalization) of maize kernels. This article summarizes the current knowledge on [...] Read more.

Tortillas are a traditional staple food in Mesoamerican cuisine, which have also become popular on a global level, e.g., for wraps or as snacks (tortilla chips). Traditional tortilla production includes alkaline cooking (nixtamalization) of maize kernels. This article summarizes the current knowledge on mycotoxin changes during the nixtamalization of maize and tortilla production. Upon nixtamalization, mycotoxins can be affected in different ways. On the one hand, the toxins can be physically removed during steeping and washing. On the other hand, mycotoxins might be degraded, modified, or released/bound in the matrix by high pH and/or high temperature. This also applies to the subsequent baking of tortillas. Many studies have shown reduced mycotoxin levels in alkali-cooked maize and in tortillas. Most of the available data relate to aflatoxins and fumonisins. The reduction (and detoxification) of aflatoxins during nixtamalization might, however, be partially reversed in acidic conditions. The loss of fumonisin concentrations is to some extent accompanied by hydrolyzation and by lower toxicity. However, some studies have indicated the potential formation of toxicologically relevant modified forms and matrix-associated fumonisins. More data are required to assess the influence of alkaline cooking regarding such modified forms, as well as mycotoxins other than aflatoxins/fumonisins. Full article

(This article belongs to the Special Issue Fate of Free, “Masked” and Conjugated/Modified forms of Mycotoxins)

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12 pages, 2837 KiB

Open AccessEditor’s ChoiceArticle

l-Proline Alleviates Kidney Injury Caused by AFB1 and AFM1 through Regulating Excessive Apoptosis of Kidney Cells

by Huiying Li, Songli Li, Huaigu Yang, Yizhen Wang, Jiaqi Wang and Nan Zheng

Toxins 2019, 11(4), 226; https://doi.org/10.3390/toxins11040226 - 16 Apr 2019

Cited by 45 | Viewed by 4609

Abstract

The toxicity and related mechanisms of aflatoxin B1 (AFB1) and aflatoxin M1 (AFM1) in the mouse kidney were studied, and the role of l-proline in alleviating kidney damage was investigated. In a 28-day toxicity mouse model, thirty mice were divided into six [...] Read more.

The toxicity and related mechanisms of aflatoxin B1 (AFB1) and aflatoxin M1 (AFM1) in the mouse kidney were studied, and the role of l-proline in alleviating kidney damage was investigated. In a 28-day toxicity mouse model, thirty mice were divided into six groups: control (without treatment), l-proline group (10 g/kg body weight (b.w.)), AFB1 group (0.5 mg/kg b.w.), AFM1 (3.5 mg/kg b.w.), AFB1 + l-proline group and AFM1 + l-proline group. Kidney index and biochemical indicators were detected, and pathological staining was observed. Using a human embryonic kidney 293 (HEK 293) cell model, cell apoptosis rate and apoptotic proteins expressions were detected. The results showed that AFB1 and AFM1 activated pathways related with oxidative stress and caused kidney injury; l-proline significantly alleviated abnormal expressions of biochemical parameters and pathological kidney damage, as well as excessive cell apoptosis in the AF-treated models. Moreover, proline dehydrogenase (PRODH) was verified to regulate the levels of l-proline and downstream apoptotic factors (Bax, Bcl-2, and cleaved Caspase-3) compared with the control (p < 0.05). In conclusion, l-proline could protect mouse kidneys from AFB1 and AFM1 through alleviating oxidative damage and decreasing downstream apoptosis, which deserves further research and development. Full article

(This article belongs to the Special Issue Fungal Infestations in Humans, Animals, Crops)

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15 pages, 2622 KiB

Open AccessArticle

Application of an Endothelial Cell Culture Assay for the Detection of Neutralizing Anti-Clostridium Perfringens Beta-Toxin Antibodies in a Porcine Vaccination Trial

by Olivia K. Richard, Sven Springer, Jacqueline Finzel, Tobias Theuß, Marianne Wyder, Beatriz Vidondo and Horst Posthaus

Toxins 2019, 11(4), 225; https://doi.org/10.3390/toxins11040225 - 15 Apr 2019

Cited by 6 | Viewed by 4172

Abstract

Background: Beta-toxin (CPB) is the major virulence factor of Clostridium perfringens type C, causing hemorrhagic enteritis in newborn pigs but also other animals and humans. Vaccines containing inactivated CPB are known to induce protective antibody titers in sow colostrum and neutralization of the [...] Read more.

Background: Beta-toxin (CPB) is the major virulence factor of Clostridium perfringens type C, causing hemorrhagic enteritis in newborn pigs but also other animals and humans. Vaccines containing inactivated CPB are known to induce protective antibody titers in sow colostrum and neutralization of the CPB activity is thought to be essential for protective immunity in newborn piglets. However, no method is available to quantify the neutralizing effect of vaccine-induced antibody titers in pigs. (2) Methods: We developed a novel assay for the quantification of neutralizing anti-CPB antibodies. Sera and colostrum of sows immunized with a commercial C. perfringens type A and C vaccine was used to determine neutralizing effects on CPB induced cytotoxicity in endothelial cells. Antibody titers of sows and their piglets were determined and compared to results obtained by an ELISA. (3) Results: Vaccinated sows developed neutralizing antibodies against CPB in serum and colostrum. Multiparous sows developed higher serum and colostrum antibody titers after booster vaccinations than uniparous sows. The antibody titers of sows and those of their piglets correlated highly. Piglets from vaccinated sows were protected against intraperitoneal challenge with C. perfringens type C supernatant. (4) Conclusions: The test based on primary porcine endothelial cells quantifies neutralizing antibody activity in serum and colostrum of vaccinated sows and could be used to reduce and refine animal experimentation during vaccine development. Full article

(This article belongs to the Collection Clostridium difficile/Clostridium sordellii and Clostridium perfringens Toxins)

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10 pages, 981 KiB

Open AccessEditor’s ChoiceArticle

Occurrence of Mycotoxigenic Fusarium Species and Competitive Fungi on Preharvest Maize Ear Rot in Poland

by Karolina Gromadzka, Lidia Błaszczyk, Jerzy Chełkowski and Agnieszka Waśkiewicz

Toxins 2019, 11(4), 224; https://doi.org/10.3390/toxins11040224 - 15 Apr 2019

Cited by 19 | Viewed by 4523

Abstract

Maize has become one of the most important crops for food and feed production—both as a silage and crop residue worldwide. The present study aimed to identify the co-occurrence of Fusarium subglutinans, Fusarium verticillioides, Trichoderma atroviride, Sarocladium zeae, and Lecanicillium [...] Read more.

Maize has become one of the most important crops for food and feed production—both as a silage and crop residue worldwide. The present study aimed to identify the co-occurrence of Fusarium subglutinans, Fusarium verticillioides, Trichoderma atroviride, Sarocladium zeae, and Lecanicillium lecanii on maize ear rot. Further, the accumulation of mycotoxins as secondary metabolites of Fusarium spp. in maize ear samples was also analyzed. Maize ear samples were collected between 2014 and 2017 from two main maize growing areas in Poland (Greater Poland and Silesia region). A significant difference was found in the frequency of two main Fusarium spp. that infect maize ears, namely F. subglutinans and F. verticillioides. In addition to Fusarium spp. T. atroviride, S. zeae, and L. lecanii were also identified. T. atroviride species was found in 14% of maize samples examined between 2014 and 2017, particularly with a high percentage of Trichoderma spp. recorded in 2014, i.e., in 31% of samples. However, mycotoxin content (beauvericin and fumonisins) varied, depending on both the location and year of sampling. The interaction of fungi and insects inhabiting maize ear and kernel is very complex and not yet elucidated. Therefore, further research is required in this area. Full article

(This article belongs to the Special Issue Fungal Infestations in Humans, Animals, Crops)

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16 pages, 3209 KiB

Open AccessArticle

Production of Cyanotoxins by Microcystis aeruginosa Mediates Interactions with the Mixotrophic Flagellate Cryptomonas

by Sarah DeVaul Princiotta, Susan P. Hendricks and David S. White

Toxins 2019, 11(4), 223; https://doi.org/10.3390/toxins11040223 - 15 Apr 2019

Cited by 19 | Viewed by 4300

Abstract

Eutrophication of inland waters is expected to increase the frequency and severity of harmful algal blooms (HABs). Toxin-production associated with HABs has negative effects on human health and aquatic ecosystem functioning. Despite evidence that flagellates can ingest toxin-producing cyanobacteria, interactions between members of [...] Read more.

Eutrophication of inland waters is expected to increase the frequency and severity of harmful algal blooms (HABs). Toxin-production associated with HABs has negative effects on human health and aquatic ecosystem functioning. Despite evidence that flagellates can ingest toxin-producing cyanobacteria, interactions between members of the microbial loop are underestimated in our understanding of the food web and algal bloom dynamics. Physical and allelopathic interactions between a mixotrophic flagellate (Cryptomonas sp.) and two strains of a cyanobacteria (Microcystis aeruginosa) were investigated in a full-factorial experiment in culture. The maximum population growth rate of the mixotroph (0.25 day⁻¹) occurred during incubation with filtrate from toxic M. aeruginosa. Cryptomonas was able to ingest toxic and non-toxic M. aeruginosa at maximal rates of 0.5 and 0.3 cells day⁻¹, respectively. The results establish that although Cryptomonas does not derive benefits from co-incubation with M. aeruginosa, it may obtain nutritional supplement from filtrate. We also provide evidence of a reduction in cyanotoxin concentration (microcystin-LR) when toxic M. aeruginosa is incubated with the mixotroph. Our work has implications for “trophic upgrading” within the microbial food web, where cyanobacterivory by nanoflagellates may improve food quality for higher trophic levels and detoxify secondary compounds. Full article

(This article belongs to the Special Issue Environmental Drivers of Algal and Cyanobacterial Toxin Dynamics)

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21 pages, 1523 KiB

Open AccessEditor’s ChoiceArticle

Development and Validation of a Liquid Chromatography High-Resolution Mass Spectrometry Method for the Simultaneous Determination of Mycotoxins and Phytoestrogens in Plant-Based Fish Feed and Exposed Fish

by Amritha Johny, Christiane Kruse Fæste, André S. Bogevik, Gerd Marit Berge, Jorge M.O. Fernandes and Lada Ivanova

Toxins 2019, 11(4), 222; https://doi.org/10.3390/toxins11040222 - 13 Apr 2019

Cited by 19 | Viewed by 5496

Abstract

New protein sources in fish feed require the assessment of the carry-over potential of contaminants and anti-nutrients from feed ingredients into the fish, and the assessment of possible health risks for consumers. Presently, plant materials including wheat and legumes make up the largest [...] Read more.

New protein sources in fish feed require the assessment of the carry-over potential of contaminants and anti-nutrients from feed ingredients into the fish, and the assessment of possible health risks for consumers. Presently, plant materials including wheat and legumes make up the largest part of aquafeeds, so evaluation of the transfer capabilities of typical toxic metabolites from plant-infesting fungi and of vegetable phytoestrogens into fish products is of great importance. With the aim of facilitating surveillance of relevant mycotoxins and isoflavones, we have developed and validated a multi-analyte LC-HRMS/MS method that can be used to ensure compliance to set maximum levels in feed and fish. The method performance characteristics were determined, showing high specificity for all 25 targeted analytes, which included 19 mycotoxins and three isoflavones and their corresponding aglycons with sufficient to excellent sensitivities and uniform analytical linearity in different matrices. Depending on the availability of matching stable isotope-labelled derivates or similar-structure homologues, calibration curves were generated either by using internal standards or by matrix-matched external standards. Precision and recovery data were in the accepted range, although they varied between the different analytes. This new method was considered as fit-for-purpose and applied for the analysis of customised fish feed containing wheat gluten, soy, or pea protein concentrate as well as salmon and zebrafish fed on diets with these ingredients for a period of up to eight weeks. Only mycotoxin enniatin B, at a level near the limit of detection, and low levels of isoflavones were detected in the feed, demonstrating the effectiveness of maximum level recommendations and modern feed processing technologies in the Norwegian aquaculture industry. Consequently, carry-over into fish muscle was not observed, confirming that fillets from plant-fed salmon were safe for human consumption. Full article

(This article belongs to the Special Issue Mycotoxins in Feed and Food Chain: Present Status and Future Concerns)

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13 pages, 3292 KiB

Open AccessEditor’s ChoiceArticle

An Attempt to Characterize the Ciguatoxin Profile in Seriola fasciata Causing Ciguatera Fish Poisoning in Macaronesia

by Pablo Estevez, David Castro, Ana Pequeño-Valtierra, José M. Leao, Oscar Vilariño, Jorge Diogène and Ana Gago-Martínez

Toxins 2019, 11(4), 221; https://doi.org/10.3390/toxins11040221 - 13 Apr 2019

Cited by 38 | Viewed by 4499

Abstract

Ciguatera Fish Poisoning is a worldwide concern caused by the consumption of fish contaminated with ciguatoxins not only in endemic regions in the Pacific Ocean or the Caribbean Sea but also in emerging areas of Macaronesia on the eastern Atlantic. The recent emergence [...] Read more.

Ciguatera Fish Poisoning is a worldwide concern caused by the consumption of fish contaminated with ciguatoxins not only in endemic regions in the Pacific Ocean or the Caribbean Sea but also in emerging areas of Macaronesia on the eastern Atlantic. The recent emergence of these toxins in other coastal areas worldwide, prompted the need for the characterization of the risk in these areas. This Ciguatera Fish Poisoning risk has been recently identified as a potential threat in subtropical areas of the Atlantic coast and scientific efforts are being focused in the identification and confirmation of the toxins involved in this potential risk. Neuroblastoma cell assay has been widely used for the evaluation of the toxicity in several marine biotoxin groups, and found to be a very useful tool for toxicity screening. LC-MS/MS has been also used for confirmatory purposes although the main limitation of the advances on LC-MS/MS development is due to commercial unavailability of reference materials and hampers method implementation and validation or even confirmation of the ciguatoxins (CTXs) responsible for the toxic profiles. While neuroblastoma cell assay (N2a) is typically used for toxicity screening as mentioned above, being necessary to confirm this N2a toxicity by LC-MS/MS, this study is designed using N2a as a tool to confirm the toxicity of the fractions obtained corresponding to potential CTXs analogues according to the analysis by LC-MS/MS. With this aim, an amberjack sample (Seriola fasciata) from Selvagen Islads (Portugal) and implicated in Ciguatera Fish Poisoning was analyzed by LC-MS/MS and Caribbean Ciguatoxins were found to be mainly responsible for the toxicity. N2a was used in this work as a tool to help in the confirmation of the toxicity of fractions obtained by HPLC. Caribbean Ciguatoxin-1 was found as the main analogue responsible for the N2a toxicity while three Caribbean Ciguatoxin-1 (C-CTX1) metabolites which contribute to the total toxicity were also identified. Full article

(This article belongs to the Special Issue Emerging Marine Biotoxins)

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18 pages, 3820 KiB

Open AccessArticle

Toxicity of Cyanopeptides from Two Microcystis Strains on Larval Development of Astyanax altiparanae

by Kelly Fernandes, Andreia Gomes, Leonardo Calado, George Yasui, Diego Assis, Theodore Henry, Ana Fonseca and Ernani Pinto

Toxins 2019, 11(4), 220; https://doi.org/10.3390/toxins11040220 - 13 Apr 2019

Cited by 25 | Viewed by 4852

Abstract

Absorption and accumulation of bioavailable cyanobacterial metabolites (including cyanotoxins) are likely in fish after senescence and the rupturing of cells during bloom episodes. We determined the toxicity of cyanopeptides identified from two strains of Microcystis (M. panniformis MIRS-04 and M. aeruginosa NPDC-01) [...] Read more.

Absorption and accumulation of bioavailable cyanobacterial metabolites (including cyanotoxins) are likely in fish after senescence and the rupturing of cells during bloom episodes. We determined the toxicity of cyanopeptides identified from two strains of Microcystis (M. panniformis MIRS-04 and M. aeruginosa NPDC-01) in a freshwater tropical fish, Astyanax altiparanae (yellowtail tetra, lambari). Aqueous extracts of both Microcystis strains were prepared in order to simulate realistic fish exposure to these substances in a freshwater environment. Both strains were selected because previous assays evidenced the presence of microcystins (MCs) in MIRS-04 and lack of cyanotoxins in NPDC-01. Identification of cyanobacterial secondary metabolites was performed by LC-HR-QTOF-MS and quantification of the MC-LR was carried out by LC-QqQ-MS/MS. MIRS-04 produces the MCs MC-LR, MC-LY and MC-HilR as well as micropeptins B, 973, 959 and k139. NPCD-01 biosynthetizes microginins FR1, FR2/FR4 and SD-755, but does not produce MCs. Larval fish survival and changes in morphology were assessed for 96 h exposure to aqueous extracts of both strains at environmentally relevant concentrations from 0.1 to 0.5 mg (dry weight)/mL, corresponding to 0.15 to 0.74 μg/mL of MC-LR (considering dried amounts of MIRS-04 for comparison). Fish mortality increased with concentration and time of exposure for both strains of Microcystis. The frequencies of morphological abnormalities increased with concentration in both strains, and included abdominal and pericardial oedema, and spinal curvature. Results demonstrate that toxicity was not solely caused by MCs, other classes of cyanobacterial secondary metabolites contributed to the observed toxicity. Full article

(This article belongs to the Collection Toxicological Challenges of Aquatic Toxins)

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12 pages, 2700 KiB

Open AccessEditor’s ChoiceCommunication

Mycotoxin Decontamination Efficacy of Atmospheric Pressure Air Plasma

by Nataša Hojnik, Martina Modic, Gabrijela Tavčar-Kalcher, Janja Babič, James L. Walsh and Uroš Cvelbar

Toxins 2019, 11(4), 219; https://doi.org/10.3390/toxins11040219 - 12 Apr 2019

Cited by 48 | Viewed by 6018

Abstract

Mycotoxins, the toxic secondary metabolites of mould species, are a growing global concern, rendering almost 25% of all food produced unfit for human or animal consumption, thus placing immense pressure on the food supply chain. Cold Atmospheric pressure Plasma (CAP) represents a promising, [...] Read more.

Mycotoxins, the toxic secondary metabolites of mould species, are a growing global concern, rendering almost 25% of all food produced unfit for human or animal consumption, thus placing immense pressure on the food supply chain. Cold Atmospheric pressure Plasma (CAP) represents a promising, low-cost, and environmentally friendly means to degrade mycotoxins with negligible effect on the quality of food products. Despite this promise, the study of CAP-mediated mycotoxin degradation has been limited to a small subset of the vast number of mycotoxins that plague the food supply chain. This study explores the degradation of aflatoxins, trichothecenes, fumonisins, and zearalenone using CAP generated in ambient air. CAP treatment was found to reduce aflatoxins by 93%, trichothecenes by 90%, fumonisins by 93%, and zearalenone by 100% after 8 minutes exposure. To demonstrate the potential of CAP-mediated mycotoxin degradation against more conventional methods, its efficiency was compared against ultraviolet C (UVC) light irradiation. In all cases, CAP was found to be considerably more efficient than UVC, with aflatoxin G₁ and zearalenone being completely degraded, levels that could not be achieved using UVC irradiation. Full article

(This article belongs to the Special Issue Biological Control and Post-Harvest Detoxification of Mycotoxins as Strategies to Reduce the Impact of Mycotoxins)

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16 pages, 2688 KiB

Open AccessArticle

Lipopolysaccharides from Microcystis Cyanobacteria-Dominated Water Bloom and from Laboratory Cultures Trigger Human Immune Innate Response

by Zdena Moosová, Lenka Šindlerová, Barbora Ambrůzová, Gabriela Ambrožová, Ondřej Vašíček, Mirna Velki, Pavel Babica and Lukáš Kubala

Toxins 2019, 11(4), 218; https://doi.org/10.3390/toxins11040218 - 11 Apr 2019

Cited by 18 | Viewed by 3930

Abstract

Massive toxic blooms of cyanobacteria represent a major threat to water supplies worldwide. Here, the biological activities of lipopolysaccharide (LPS) isolated from Microcystis aeruginosa, the most prominent cyanobacteria in water bloom, were studied. LPS was isolated from complex environmental water bloom samples [...] Read more.

Massive toxic blooms of cyanobacteria represent a major threat to water supplies worldwide. Here, the biological activities of lipopolysaccharide (LPS) isolated from Microcystis aeruginosa, the most prominent cyanobacteria in water bloom, were studied. LPS was isolated from complex environmental water bloom samples dominated by M. aeruginosa, and from laboratory cultures of non-axenic as well as axenic M. aeruginosa strains PCC7806 and HAMBI/UHCC130. Employing human blood-based in vitro tests, the LPS isolated from complex water bloom revealed the priming of both major blood phagocyte population monocytes and polymorphonuclear leukocytes documented by the increased surface expression of CD11b and CD66b. This was accompanied by a water bloom LPS-mediated dose-dependent induction of tumor necrosis factor α, interleukin-1β, and interleukin-6 production. In accordance with its priming effects, water bloom LPS induced significant activation of p38 and ERK1/2 kinases, as well as NF-κB phosphorylation, in isolated polymorphonuclear leukocytes. Interestingly, the pro-inflammatory potential of LPS from the axenic strain of M. aeruginosa was not lower compared to that of LPS isolated from non-axenic strains. In contrast to the biological activity, water bloom LPS revealed almost twice higher pyrogenicity levels compared to Escherichia coli LPS, as analyzed by the PyroGene test. Moreover, LPS from the non-axenic culture exhibited higher endotoxin activity in comparison to LPS from axenic strains. Taking the above findings together, M. aeruginosa LPS can contribute to the health risks associated with contamination by complex water bloom mass. Full article

(This article belongs to the Special Issue Freshwater Cyanobacterial Toxins: Developments in Monitoring, Identification, Impacts and Factors Influencing Production)

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11 pages, 6386 KiB

Open AccessArticle

Assessment of Toxic Effects of Ochratoxin A in Human Embryonic Stem Cells

by Slaven Erceg, Eva María Mateo, Iván Zipancic, Francisco Javier Rodríguez Jiménez, María Amparo Pérez Aragó, Misericordia Jiménez, José Miguel Soria and Mª Ángeles Garcia-Esparza

Toxins 2019, 11(4), 217; https://doi.org/10.3390/toxins11040217 - 10 Apr 2019

Cited by 21 | Viewed by 5506

Abstract

Ochratoxin A (OTA) is a mycotoxin produced by different Aspergillus and Penicillium species, and it is considered a common contaminant in food and animal feed worldwide. On the other hand, human embryonic stem cells (hESCs) have been suggested as a valuable model for [...] Read more.

Ochratoxin A (OTA) is a mycotoxin produced by different Aspergillus and Penicillium species, and it is considered a common contaminant in food and animal feed worldwide. On the other hand, human embryonic stem cells (hESCs) have been suggested as a valuable model for evaluating drug embryotoxicity. In this study, we have evaluated potentially toxic effects of OTA in hESCs. By using in vitro culture techniques, specific cellular markers, and molecular biology procedures, we found that OTA produces mild cytotoxic effects in hESCs by inhibiting cell attachment, survival, and proliferation in a dose-dependent manner. Thus, we suggest that hESCs provide a valuable human and cellular model for toxicological studies regarding preimplantation stage of human fetal development. Full article

(This article belongs to the Special Issue Toxicological Effects of Mycotoxins on Target Cells)

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18 pages, 3884 KiB

Open AccessEditor’s ChoiceArticle

Antimicrobial and Antibiofilm Effects of Peptides from Venom of Social Wasp and Scorpion on Multidrug-Resistant Acinetobacter baumannii

by Rogério Coutinho das Neves, Márcia Renata Mortari, Elisabeth Ferroni Schwartz, André Kipnis and Ana Paula Junqueira-Kipnis

Toxins 2019, 11(4), 216; https://doi.org/10.3390/toxins11040216 - 10 Apr 2019

Cited by 28 | Viewed by 5549

Abstract

Intravascular stent infection is a rare complication with a high morbidity and high mortality; bacteria from the hospital environment form biofilms and are often multidrug-resistant (MDR). Antimicrobial peptides (AMPs) have been considered as alternatives to bacterial infection treatment. We analyzed the formation of [...] Read more.

Intravascular stent infection is a rare complication with a high morbidity and high mortality; bacteria from the hospital environment form biofilms and are often multidrug-resistant (MDR). Antimicrobial peptides (AMPs) have been considered as alternatives to bacterial infection treatment. We analyzed the formation of the bacterial biofilm on the vascular stents and also tested the inhibition of this biofilm by AMPs to be used as treatment or coating. Antimicrobial activity and antibiofilm were tested with wasp (Agelaia-MPI, Polybia-MPII, Polydim-I) and scorpion (Con10 and NDBP5.8) AMPs against Acinetobacter baumannii clinical strains. A. baumannii formed a biofilm on the vascular stent. Agelaia-MPI and Polybia-MPII inhibited biofilm formation with bacterial cell wall degradation. Coating biofilms with polyethylene glycol (PEG 400) and Agelaia-MPI reduced 90% of A. baumannii adhesion on stents. The wasp AMPs Agelaia-MPI and Polybia-MPII had better action against MDR A. baumannii adherence and biofilm formation on vascular stents, preventing its formation and treating mature biofilm when compared to the other tested peptides. Full article

(This article belongs to the Special Issue Arthropod Venom Components and Their Potential Usage)

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16 pages, 1084 KiB

Open AccessEditor’s ChoiceArticle

Fumonisin Production by Fusarium verticillioides in Maize Genotypes Cultivated in Different Environments

by Oelton Ferreira Rosa Junior, Mateus Sunti Dalcin, Vitor L. Nascimento, Fernando Machado Haesbaert, Talita Pereira de Souza Ferreira, Rodrigo Ribeiro Fidelis, Renato de Almeida Sarmento, Raimundo Wagner de Souza Aguiar, Eugenio Eduardo de Oliveira and Gil Rodrigues dos Santos

Toxins 2019, 11(4), 215; https://doi.org/10.3390/toxins11040215 - 10 Apr 2019

Cited by 30 | Viewed by 5086

Abstract

Fumonisins are mycotoxins (MTs) produced mainly by the fungus Fusarium verticillioides, the main pathogens of maize which cause ear rot. The aim of this work was to evaluate some factors that may lead to high fumonisin production by F. verticillioides in maize [...] Read more.

Fumonisins are mycotoxins (MTs) produced mainly by the fungus Fusarium verticillioides, the main pathogens of maize which cause ear rot. The aim of this work was to evaluate some factors that may lead to high fumonisin production by F. verticillioides in maize grains, correlating the pathogen inoculation method with different genotypes grown in four Brazilian states. Experiments were conducted in 2015–2016 in maize crops from experimental maize fields located in four distinct states of Brazil. Results showed that contamination by fumonisin mycotoxins occurred even on symptomatic or asymptomatic grains. In all municipalities, the samples showed levels of fumonisin B1 that were higher than would be tolerable for the human consumption of corn products (the current tolerance limit for fumonisin is 1.5 μg g⁻¹). High severity of grains infected with F. verticillioides does not always show high concentrations of fumonisins. Environments with higher temperatures may influence the production of high concentrations of fumonisin in maize hybrids. Spray inoculation methods and inoculation at the center of spikes did not influence fumonisin concentrations. Results showed that the hybrids P3630H, P32R48 and P3250 presented higher disease severity, as well as higher mycotoxin levels in the studied locations with higher temperatures. Full article

(This article belongs to the Section Mycotoxins)

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14 pages, 3209 KiB

Open AccessEditor’s ChoiceArticle

Fluorescence Spectroscopic Investigation of Competitive Interactions between Quercetin and Aflatoxin B₁ for Binding to Human Serum Albumin

by Hongxia Tan, Lu Chen, Liang Ma, Shuang Liu, Hongyuan Zhou, Yuhao Zhang, Ting Guo, Wei Liu, Hongjie Dai and Yong Yu

Toxins 2019, 11(4), 214; https://doi.org/10.3390/toxins11040214 - 9 Apr 2019

Cited by 30 | Viewed by 4658

Abstract

Aflatoxin B₁ (AFB₁) is a highly toxic mycotoxin found worldwide in cereals, food, and animal feeds. AFB₁ binds to human serum albumin (HSA) with high affinity. In previous experiments, it has been revealed that reducing the binding rate of [...] Read more.

Aflatoxin B₁ (AFB₁) is a highly toxic mycotoxin found worldwide in cereals, food, and animal feeds. AFB₁ binds to human serum albumin (HSA) with high affinity. In previous experiments, it has been revealed that reducing the binding rate of AFB₁ with HSA could speed up the elimination rate of AFB₁. Therefore, we examined the ability of quercetin to compete with AFB₁ for binding HSA by fluorescence spectroscopy, synchronous spectroscopy, ultrafiltration studies, etc. It was shown that AFB₁ and quercetin bind to HSA in the same Sudlow site I (subdomain IIA), and the binding constant (K_a) of the quercetin-HSA complex is significantly stronger than the complex of AFB₁-HSA. Our data in this experiment showed that quercetin is able to remove the AFB₁ from HSA and reduce its bound fraction. This exploratory work may be of significance for studies in the future regarding decreasing its bound fraction and then increasing its elimination rate for detoxification. This exploratory study may initiate future epidemiological research designs to obtain further in vivo evidence of the long-term (potential protective) effects of competing substances on human patients. Full article

(This article belongs to the Special Issue 2^nd MycoKey International Conference - Integrated Solutions for Mycotoxin Management)

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13 pages, 929 KiB

Open AccessEditor’s ChoiceReview

The Key Role of Phosphate on Vascular Calcification

by Mario Cozzolino, Paola Ciceri, Andrea Galassi, Michela Mangano, Stefano Carugo, Irene Capelli and Giuseppe Cianciolo

Toxins 2019, 11(4), 213; https://doi.org/10.3390/toxins11040213 - 9 Apr 2019

Cited by 109 | Viewed by 10987

Abstract

Vascular calcification (VC) is common in dialysis and non-dialysis chronic kidney disease (CKD) patients, even in the early stage of the disease. For this reason, it can be considered a CKD hallmark. VC contributes to cardiovascular disease (CVD) and increased mortality among CKD [...] Read more.

Vascular calcification (VC) is common in dialysis and non-dialysis chronic kidney disease (CKD) patients, even in the early stage of the disease. For this reason, it can be considered a CKD hallmark. VC contributes to cardiovascular disease (CVD) and increased mortality among CKD patients, although it has not been proven. There are more than one type of VC and every form represents a marker of systemic vascular disease and is associated with a higher prevalence of CVD in CKD patients, as shown by several clinical studies. Major risk factors for VC in CKD include: Increasing age, dialysis vintage, hyperphosphatemia (particularly in the setting of intermittent or persistent hypercalcemia), and a positive net calcium and phosphate balance. Excessive oral calcium intake, including calcium-containing phosphate binders, increases the risk for VC. Moreover, it has been demonstrated that there is less VC progression with non-calcium-containing phosphate binders. Unfortunately, until now, a specific therapy to prevent progression or to facilitate regression of VC has been found, beyond careful attention to calcium and phosphate balance. Full article

(This article belongs to the Special Issue The Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD))

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26 pages, 1928 KiB

Open AccessEditor’s ChoiceReview

Roles of Shiga Toxins in Immunopathology

by Moo-Seung Lee and Vernon L. Tesh

Toxins 2019, 11(4), 212; https://doi.org/10.3390/toxins11040212 - 9 Apr 2019

Cited by 62 | Viewed by 11010

Abstract

Shigella species and Shiga toxin-producing Escherichia coli (STEC) are agents of bloody diarrhea that may progress to potentially lethal complications such as diarrhea-associated hemolytic uremic syndrome (D+HUS) and neurological disorders. The bacteria share the ability to produce virulence factors called Shiga toxins (Stxs). [...] Read more.

Shigella species and Shiga toxin-producing Escherichia coli (STEC) are agents of bloody diarrhea that may progress to potentially lethal complications such as diarrhea-associated hemolytic uremic syndrome (D+HUS) and neurological disorders. The bacteria share the ability to produce virulence factors called Shiga toxins (Stxs). Research over the past two decades has identified Stxs as multifunctional toxins capable of inducing cell stress responses in addition to their canonical ribotoxic function inhibiting protein synthesis. Notably, Stxs are not only potent inducers of cell death, but also activate innate immune responses that may lead to inflammation, and these effects may increase the severity of organ injury in patients infected with Stx-producing bacteria. In the intestines, kidneys, and central nervous system, excessive or uncontrolled host innate and cellular immune responses triggered by Stxs may result in sensitization of cells to toxin mediated damage, leading to immunopathology and increased morbidity and mortality in animal models (including primates) and human patients. Here, we review studies describing Stx-induced innate immune responses that may be associated with tissue damage, inflammation, and complement activation. We speculate on how these processes may contribute to immunopathological responses to the toxins. Full article

(This article belongs to the Special Issue Toxins and Immunology)

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13 pages, 2152 KiB

Open AccessArticle

¹⁵N Stable Isotope Labeling PSTs in Alexandrium minutum for Application of PSTs as Biomarker

by Wancui Xie, Min Li, Lin Song, Rui Zhang, Xiaoqun Hu, Chengzhu Liang and Xihong Yang

Toxins 2019, 11(4), 211; https://doi.org/10.3390/toxins11040211 - 8 Apr 2019

Cited by 2 | Viewed by 3524

Abstract

The dinoflagellate Alexandrium minutum (A. minutum) which can produce paralytic shellfish toxins (PSTs) is often used as a model to study the migration, biotransformation, accumulation, and removal of PSTs. However, the mechanism is still unclear. To provide a new tool for [...] Read more.

The dinoflagellate Alexandrium minutum (A. minutum) which can produce paralytic shellfish toxins (PSTs) is often used as a model to study the migration, biotransformation, accumulation, and removal of PSTs. However, the mechanism is still unclear. To provide a new tool for related studies, we tried to label PSTs metabolically with ¹⁵N stable isotope to obtain ¹⁵N-PSTs instead of original ¹⁴N, which could be treated as biomarker on PSTs metabolism. We then cultured the A. minutum AGY-H46 which produces toxins GTX1-4 in f/2 medium of different ¹⁵N/P concentrations. The ¹⁵N-PSTs’ toxicity and toxin profile were detected. Meanwhile, the ¹⁵N labeling abundance and ¹⁵N atom number of ¹⁵N-PSTs were identified. The ¹⁴N of PSTs produced by A. minutum can be successfully replaced by ¹⁵N, and the f/2 medium of standard ¹⁵N/P concentration was the best choice in terms of the species’ growth, PST profile, ¹⁵N labeling result and experiment cost. After many (>15) generations, the ¹⁵N abundance in PSTs extract reached 82.36%, and the ¹⁵N atom number introduced into GTX1-4 might be 4–6. This paper innovatively provided the initial evidence that ¹⁵N isotope application of labeling PSTs in A. minutum is feasible. The ¹⁵N-PSTs as biomarker can be applied and provide further information on PSTs metabolism. Full article

(This article belongs to the Collection Toxicological Challenges of Aquatic Toxins)

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11 pages, 279 KiB

Open AccessArticle

Combined Effects of Isokinetic Training and Botulinum Toxin Type A on Spastic Equinus Foot in Patients with Chronic Stroke: A Pilot, Single-blind, Randomized Controlled Trial

by Nicoletta Cinone, Sara Letizia, Luigi Santoro, Salvatore Facciorusso, Raffaella Armiento, Alessandro Picelli, Maurizio Ranieri and Andrea Santamato

Toxins 2019, 11(4), 210; https://doi.org/10.3390/toxins11040210 - 8 Apr 2019

Cited by 15 | Viewed by 5026

Abstract

Botulinum toxin A (BoNT-A) has been shown effective for poststroke lower limb spasticity. Following injections, a wide range of multidisciplinary approach has been previously provided. The purpose of this pilot, single-blind, randomized controlled trial was to determine whether BoNT-A combined with a regime [...] Read more.

Botulinum toxin A (BoNT-A) has been shown effective for poststroke lower limb spasticity. Following injections, a wide range of multidisciplinary approach has been previously provided. The purpose of this pilot, single-blind, randomized controlled trial was to determine whether BoNT-A combined with a regime of a four-week ankle isokinetic treatment has a positive effect on function and spasticity, compared with BoNT-A alone. Secondly, the validity of the use of an isokinetic dynamometer to measure the stretch reflex at the ankle joint and residual strength has been investigated. Twenty-five chronic stroke patients were randomized to receive combined treatment (n = 12; experimental group) or BoNT-A alone (n = 13; control group). Outcome measures were based on the International Classification of Functioning, Disability and Health. An isokinetic dynamometer was also used for stretch reflex and strength assessment. Patients were evaluated at baseline (t0), after five (t1) and eight weeks after the injection (t2). The experimental group reported significantly greater improvements on lower limb spasticity, especially after eight weeks from baseline. Gait speed (10-m walk test) and walking capacity (6-min walking test) revealed statistically significantly better improvement in the experimental than in control group. Peak resistive ankle torque during growing angular velocities showed a significant reduction at the higher velocities after BoNT-A injections in the experimental group. Peak dorsiflexor torque was significantly increased in the experimental group and peak plantarflexor torque was significantly decreased in control group. Alternative rehabilitation strategies that combine BoNT-A and an intense ankle isokinetic treatment are effective in reducing tone and improving residual strength and motor function in patients with chronic hemiparesis. Full article

(This article belongs to the Special Issue Botulinum Toxin: The Role in Neuro-Rehabilitation)

18 pages, 696 KiB

Open AccessReview

Emerging Roles of Aryl Hydrocarbon Receptors in the Altered Clearance of Drugs during Chronic Kidney Disease

by Tacy Santana Machado, Claire Cerini and Stéphane Burtey

Toxins 2019, 11(4), 209; https://doi.org/10.3390/toxins11040209 - 7 Apr 2019

Cited by 14 | Viewed by 4572

Abstract

Chronic kidney disease (CKD) is a major public health problem, since 300,000,000 people in the world display a glomerular filtration rate (GFR) below 60 mL/min/1.73m². Patients with CKD have high rates of complications and comorbidities. Thus, they require the prescription of [...] Read more.

Chronic kidney disease (CKD) is a major public health problem, since 300,000,000 people in the world display a glomerular filtration rate (GFR) below 60 mL/min/1.73m². Patients with CKD have high rates of complications and comorbidities. Thus, they require the prescription of numerous medications, making the management of patients very complex. The prescription of numerous drugs associated with an altered renal- and non-renal clearance makes dose adjustment challenging in these patients, with frequent drug-related adverse events. However, the mechanisms involved in this abnormal drug clearance during CKD are not still well identified. We propose here that the transcription factor, aryl hydrocarbon receptor, which is the cellular receptor for indolic uremic toxins, could worsen the metabolism and the excretion of drugs in CKD patients. Full article

(This article belongs to the Special Issue Disposition of Uremic Toxins: The Challenges in Uremia)

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15 pages, 1432 KiB

Open AccessEditor’s ChoiceArticle

Monoclonal Antibody Combinations Prevent Serotype A and Serotype B Inhalational Botulism in a Guinea Pig Model

by Milan T. Tomic, Yero Espinoza, Zachary Martinez, Khanh Pham, Ronald R. Cobb, Doris M. Snow, Christopher G. Earnhart, Traci Pals, Emily S. Syar, Nancy Niemuth, Dean J. Kobs, Shauna Farr-Jones and James D. Marks

Toxins 2019, 11(4), 208; https://doi.org/10.3390/toxins11040208 - 6 Apr 2019

Cited by 17 | Viewed by 5434

Abstract

Botulinum neurotoxins (BoNT) are some of the most toxic proteins known, with a human LD₅₀ of ~1 ng/kg. Equine antitoxin has a half-life in circulation of less than 1 day and is limited to a treatment rather than a prevention indication. The [...] Read more.

Botulinum neurotoxins (BoNT) are some of the most toxic proteins known, with a human LD₅₀ of ~1 ng/kg. Equine antitoxin has a half-life in circulation of less than 1 day and is limited to a treatment rather than a prevention indication. The development of monoclonal antibodies (mAbs) may represent an alternative therapeutic option that can be produced at high quantities and of high quality and with half-lives of >10 days. Two different three mAb combinations are being developed that specifically neutralize BoNT serotypes A (BoNT/A) and B (BoNT/B). We investigated the pharmacokinetics of the anti-BoNT/A and anti-BoNT/B antibodies in guinea pigs (Cavia porcellus) and their ability to protect guinea pigs against an aerosol challenge of BoNT/A1 or BoNT/B1. Each antibody exhibited dose-dependent exposure and reached maximum circulating concentrations within 48 h post intraperitoneal or intramuscular injection. A single intramuscular dose of the three mAb combination protected guinea pigs against an aerosol challenge dose of 93 LD₅₀ of BoNT/A1 and 116 LD₅₀ of BoNT/B1 at 48 h post antibody administration. These mAbs are effective in preventing botulism after an aerosol challenge of BoNT/A1 and BoNT/B1 and may represent an alternative to vaccination to prevent type A or B botulism in those at risk of BoNT exposure. Full article

(This article belongs to the Section Bacterial Toxins)

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Toxins, Volume 11, Issue 4 (April 2019) – 55 articles

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