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Toxins, Volume 14, Issue 9 (September 2022) – 71 articles

Cover Story (view full-size image): Sesquiterpenes and benzoxazinoids from natural sources were evaluated against the Mpro, RNA replicase and spike glycoprotein of SARS-CoV-2 using in silico approaches. These natural products and their derivatives have previously shown remarkable antiviral activities. The most relevant compounds were the 4-fluoro derivatives of santamarine, reynosin and 2-amino-3H-phenoxazin-3-one according to molecular docking. Those compounds fulfill oral bioavailability rules, and they displayed high compound-protein kinetic stability by molecular dynamics after a 50 ns simulation. Candidates tested in silico show that the addition of a 4-fluorobenzoate fragment to the natural products enhances their inhibition potential against the main protease, RNA replicase and spike protein of SARS-CoV-2. View this paper
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47 pages, 498 KiB  
Review
Mycotoxins Contamination in Rice: Analytical Methods, Occurrence and Detoxification Strategies
by Ana Rita Santos, Filipa Carreiró, Andreia Freitas, Sílvia Barros, Carla Brites, Fernando Ramos and Ana Sanches Silva
Toxins 2022, 14(9), 647; https://doi.org/10.3390/toxins14090647 - 19 Sep 2022
Cited by 21 | Viewed by 4720
Abstract
The prevalence of mycotoxins in the environment is associated with potential crop contamination, which results in an unavoidable increase in human exposure. Rice, being the second most consumed cereal worldwide, constitutes an important source of potential contamination by mycotoxins. Due to the increasing [...] Read more.
The prevalence of mycotoxins in the environment is associated with potential crop contamination, which results in an unavoidable increase in human exposure. Rice, being the second most consumed cereal worldwide, constitutes an important source of potential contamination by mycotoxins. Due to the increasing number of notifications reported, and the occurrence of mycotoxins at levels above the legislated limits, this work intends to compile the most relevant studies and review the main methods used in the detection and quantification of these compounds in rice. The aflatoxins and ochratoxin A are the predominant mycotoxins detected in rice grain and these data reveal the importance of adopting safety storage practices that prevent the growth of producing fungi from the Aspergillus genus along all the rice chain. Immunoaffinity columns (IAC) and QuECHERS are the preferred methods for extraction and purification and HPLC-MS/MS is preferred for quantification purposes. Further investigation is still required to establish the real exposition of these contaminants, as well as the consequences and possible synergistic effects due to the co-occurrence of mycotoxins and also for emergent and masked mycotoxins. Full article
(This article belongs to the Special Issue Looking Forward: Mycotoxins Occurrence and Detection in Food and Feed)
14 pages, 3441 KiB  
Article
Insecticidal Activity of Chitinases from Xenorhabdus nematophila HB310 and Its Relationship with the Toxin Complex
by Jia Liu, Hui Bai, Ping Song, Ziyan Nangong, Zhiping Dong, Zhiyong Li and Qinying Wang
Toxins 2022, 14(9), 646; https://doi.org/10.3390/toxins14090646 - 18 Sep 2022
Cited by 3 | Viewed by 1877
Abstract
Xenorhabdus nematophila HB310 secreted the insecticidal protein toxin complex (Tc). The chi60 and chi70 chitinase genes are located on the gene cluster encoding Tc toxins. To clarify the insecticidal activity of chitinases and their relationship with Tc toxins, the insecticidal activity of the [...] Read more.
Xenorhabdus nematophila HB310 secreted the insecticidal protein toxin complex (Tc). The chi60 and chi70 chitinase genes are located on the gene cluster encoding Tc toxins. To clarify the insecticidal activity of chitinases and their relationship with Tc toxins, the insecticidal activity of the chitinases was assessed on Helicoverpa armigera. Then, the chi60 and chi70 genes of X. nematophila HB310 were knocked out by the pJQ200SK suicide plasmid knockout system. The insecticidal activity of Tc toxin from the wild-type strain (WT) and mutant strains was carried out. The results demonstrate that Chi60 and Chi70 had an obvious growth inhibition effect against the second instar larvae of H. armigera with growth-inhibiting rates of 81.99% and 90.51%, respectively. Chi70 had a synergistic effect with the insecticidal toxicity of Tc toxins, but Chi60 had no synergistic effect with Tc toxins. After feeding Chi60 and Chi70, the peritrophic membrane of H. armigera became inelastic, was easily broken and leaked blue dextran. The Δchi60, Δchi70 and Δchi60-chi70 mutant strains were successfully screened. The toxicity of Tc toxins from the WT, Δchi60, Δchi70 and Δchi60-chi70 was 196.11 μg/mL, 757.25 μg/mL, 885.74 μg/mL and 20,049.83 μg/mL, respectively. The insecticidal activity of Tc toxins from Δchi60 and Δchi70 was 3.861 and 4.517 times lower than that of Tc toxins from the WT, respectively, while the insecticidal activity of Tc toxins from the Δchi60-chi70 mutant strain almost disappeared. These results indicate that the presence of chi60 and chi70 is indispensable for the toxicity of Tc toxins. Full article
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21 pages, 1512 KiB  
Review
Microbial-Derived Tryptophan Catabolites, Kidney Disease and Gut Inflammation
by Avra Melina Madella, Jeroen Van Bergenhenegouwen, Johan Garssen, Rosalinde Masereeuw and Saskia Adriana Overbeek
Toxins 2022, 14(9), 645; https://doi.org/10.3390/toxins14090645 - 18 Sep 2022
Cited by 12 | Viewed by 3720
Abstract
Uremic metabolites, molecules either produced by the host or from the microbiota population existing in the gastrointestinal tract that gets excreted by the kidneys into urine, have significant effects on both health and disease. Tryptophan-derived catabolites are an important group of bacteria-produced metabolites [...] Read more.
Uremic metabolites, molecules either produced by the host or from the microbiota population existing in the gastrointestinal tract that gets excreted by the kidneys into urine, have significant effects on both health and disease. Tryptophan-derived catabolites are an important group of bacteria-produced metabolites with an extensive contribution to intestinal health and, eventually, chronic kidney disease (CKD) progression. The end-metabolite, indoxyl sulfate, is a key contributor to the exacerbation of CKD via the induction of an inflammatory state and oxidative stress affecting various organ systems. Contrastingly, other tryptophan catabolites positively contribute to maintaining intestinal homeostasis and preventing intestinal inflammation—activities signaled through nuclear receptors in particular—the aryl hydrocarbon receptor (AhR) and the pregnane X receptor (PXR). This review discusses the origins of these catabolites, their effect on organ systems, and how these can be manipulated therapeutically in the future as a strategy to treat CKD progression and gut inflammation management. Furthermore, the use of biotics (prebiotics, probiotics, synbiotics) as a means to increase the presence of beneficial short-chain fatty acids (SCFAs) to achieve intestinal homeostasis is discussed. Full article
(This article belongs to the Special Issue Kidney Disease-Gut Dysbiosis: What Is the Role of Uremic Toxins?)
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15 pages, 1949 KiB  
Article
Comparison of Protein Variation in Protobothrops mucrosquamatus Venom between Northern and Southeast Taiwan and Association with Human Envenoming Effects
by Liao-Chun Chiang, Kun-Yi Chien, Hung-Yuan Su, Yen-Chia Chen, Yan-Chiao Mao and Wen-Guey Wu
Toxins 2022, 14(9), 643; https://doi.org/10.3390/toxins14090643 - 18 Sep 2022
Cited by 7 | Viewed by 2169
Abstract
Reports of bite from Protobothrops mucrosquamatus (Pmu) are frequent in Taiwan, and its wide-spread distribution and diverse habitats drove us to investigate its envenoming effects and relevant venom variations. We used reversed-phase high-performance liquid chromatography and mass spectrometry to analyze 163 [...] Read more.
Reports of bite from Protobothrops mucrosquamatus (Pmu) are frequent in Taiwan, and its wide-spread distribution and diverse habitats drove us to investigate its envenoming effects and relevant venom variations. We used reversed-phase high-performance liquid chromatography and mass spectrometry to analyze 163 Pmu venom samples collected from northern and southeastern Taiwan. Twenty-two major protein fractions were separated and analyzed, and their contents were determined semi-quantitatively. The results showed that despite the trivial differences in the protein family, there is an existing variation in acidic phospholipases A2s, serine proteinases, metalloproteinases, C-type lectin-like proteins, and other less abundant components in the Pmu venoms. Moreover, clinical manifestations of 209 Pmu envenomed patients hospitalized in northern or southeastern Taiwan revealed significant differences in local symptoms, such as ecchymosis and blistering. The mechanism of these local effects and possibly relevant venom components were examined. Further analysis showed that certain venom components with inter-population variation might work alone or synergistically with others to aggravate the local effects. Therefore, our findings of the venom variation may help one to improve antivenom production and better understand and manage Pmu bites. Full article
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24 pages, 2133 KiB  
Article
In Silico Conformational Features of Botulinum Toxins A1 and E1 According to Intraluminal Acidification
by Grazia Cottone, Letizia Chiodo, Luca Maragliano, Michel-Robert Popoff, Christine Rasetti-Escargueil, Emmanuel Lemichez and Thérèse E. Malliavin
Toxins 2022, 14(9), 644; https://doi.org/10.3390/toxins14090644 - 17 Sep 2022
Cited by 2 | Viewed by 1914
Abstract
Although botulinum neurotoxins (BoNTs) are among the most toxic compounds found in nature, their molecular mechanism of action is far from being elucidated. A key event is the conformational transition due to acidification of the interior of synaptic vesicles, leading to translocation of [...] Read more.
Although botulinum neurotoxins (BoNTs) are among the most toxic compounds found in nature, their molecular mechanism of action is far from being elucidated. A key event is the conformational transition due to acidification of the interior of synaptic vesicles, leading to translocation of the BoNT catalytic domain into the neuronal cytosol. To investigate these conformational variations, homology modeling and atomistic simulations are combined to explore the internal dynamics of the sub-types BoNT/A1 (the most-used sub-type in medical applications) and BoNT/E1 (the most kinetically efficient sub-type). This first simulation study of di-chain BoNTs in closed and open states considers the effects of both neutral and acidic pH. The conformational mobility is driven by domain displacements of the ganglioside-binding site in the receptor binding domain, the translocation domain (HCNT) switch, and the belt α-helix, which present multiple conformations, depending on the primary sequence and the pH. Fluctuations of the belt α-helix are observed for closed conformations of the toxins and at acidic pH, while patches of more solvent-accessible residues appear under the same conditions in the core translocation domain HCNT. These findings suggest that, during translocation, the higher mobility of the belt could be transmitted to HCNT, leading to the favorable interaction of HCNT residues with the non-polar membrane environment. Full article
(This article belongs to the Section Bacterial Toxins)
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10 pages, 942 KiB  
Article
Variation of Aflatoxin Levels in Stored Edible Seed and Oil Samples and Risk Assessment in the Local Population
by Shahzad Zafar Iqbal, Muhammad Waqas, Ahmad Faizal Abdull Razis, Sunusi Usman, Nada Basheir Ali and Muhammad Rafique Asi
Toxins 2022, 14(9), 642; https://doi.org/10.3390/toxins14090642 - 17 Sep 2022
Cited by 4 | Viewed by 1990
Abstract
Five hundred and twenty samples of edible seeds and oilseeds (sunflower, palm, peanut, sesame, cotton, and grapeseed) were purchased from markets, farmers, and superstores in the central cities of Punjab, Pakistan. A total of 125 (48.1%) edible seed samples from a 6 ≤ [...] Read more.
Five hundred and twenty samples of edible seeds and oilseeds (sunflower, palm, peanut, sesame, cotton, and grapeseed) were purchased from markets, farmers, and superstores in the central cities of Punjab, Pakistan. A total of 125 (48.1%) edible seed samples from a 6 ≤ months storage period, and 127 (48.8%) from a 2 ≥ years storage period were found to be infested with AFs. The average elevated amount of AFB1 and total AFs was observed in a 2 ≥ years storage period, i.e., 28.6 ± 4.5 and 51.3 ± 10.4 µg/kg, respectively, in sesame seeds. The minimum amount of AFB1 and total AFs was observed in palm seed samples with a storage period of 6 ≤ months, i.e., 9.96 ± 2.4, and 11.7 ± 1.90 µg/kg, respectively. The maximum amount of AFB1 and total AFs were observed in peanut oil samples, i.e., 21.43 ± 2.60 and 25.96 ± 4.30 µg/kg, respectively, with a storage period of 2 ≥ years. Therefore, the maximum dietary intake of 59.60 ng/kg/day was observed in oil samples stored at a ≥ 2 years storage period. The results of the present study concluded that a significant difference was found in the amounts of total AFs in edible seed samples stored at 6 ≤ months and 2 ≥ years storage periods (p < 0.05). Full article
(This article belongs to the Special Issue Mycotoxins in Food and Feed: Detection and Identification)
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14 pages, 2431 KiB  
Article
Resveratrol Protects against Zearalenone-Induced Mitochondrial Defects during Porcine Oocyte Maturation via PINK1/Parkin-Mediated Mitophagy
by Jiehuan Xu, Lingwei Sun, Mengqian He, Shushan Zhang, Jun Gao, Caifeng Wu, Defu Zhang and Jianjun Dai
Toxins 2022, 14(9), 641; https://doi.org/10.3390/toxins14090641 - 16 Sep 2022
Cited by 11 | Viewed by 3678
Abstract
Mitochondria hold redox homeostasis and energy metabolism as a crucial factor during oocyte maturation, while the exposure of estrogenic mycotoxin zearalenone causes developmental incapacity in porcine oocyte. This study aimed to reveal a potential resistance of phytoalexin resveratrol against zearalenone during porcine oocyte [...] Read more.
Mitochondria hold redox homeostasis and energy metabolism as a crucial factor during oocyte maturation, while the exposure of estrogenic mycotoxin zearalenone causes developmental incapacity in porcine oocyte. This study aimed to reveal a potential resistance of phytoalexin resveratrol against zearalenone during porcine oocyte maturation and whether its mechanism was related with PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy. Porcine oocytes were exposed to 20 μM zearalenone with or without 2 μM resveratrol during in vitro maturation. As for the results, zearalenone impaired ultrastructure of mitochondria, causing mitochondrial depolarization, oxidative stress, apoptosis and embryonic developmental incapacity, in which mitophagy was induced in response to mitochondrial dysfunction. Phytoalexin resveratrol enhanced mitophagy through PINK1/Parkin in zearalenone-exposed oocytes, manifesting as enhanced mitophagy flux, upregulated PINK1, Parkin, microtubule-associated protein light-chain 3 beta-II (LC3B-II) and downregulated substrates mitofusin 2 (MFN2), voltage-dependent anion channels 1 (VDAC1) and p62 expressions. Resveratrol redressed zearalenone-induced mitochondrial depolarization, oxidative stress and apoptosis, and accelerated mitochondrial DNA copy during maturation, which improved embryonic development. This study offered an antitoxin solution during porcine oocyte maturation and revealed the involvement of PINK1/Parkin-mediated mitophagy, in which resveratrol mitigated zearalenone-induced embryonic developmental incapacity. Full article
(This article belongs to the Special Issue Mycotoxins and Fungal Toxins: Current Status and Future Perspectives)
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16 pages, 2796 KiB  
Article
Ochratoxin A and Citrinin Differentially Modulate Bovine Mammary Epithelial Cell Permeability and Innate Immune Function
by Ran Xu, Umesh K. Shandilya, Alexandros Yiannikouris and Niel A. Karrow
Toxins 2022, 14(9), 640; https://doi.org/10.3390/toxins14090640 - 16 Sep 2022
Cited by 2 | Viewed by 2194
Abstract
Frequent detection of mycotoxins ochratoxin A (OTA) and citrinin (CIT) in ruminant feed and feedstuff can be a potential threat to feed safety, animal performance and health. Ineffective biodegradation of these mycotoxins by rumen microflora following ingestion of contaminated feeds can lead to [...] Read more.
Frequent detection of mycotoxins ochratoxin A (OTA) and citrinin (CIT) in ruminant feed and feedstuff can be a potential threat to feed safety, animal performance and health. Ineffective biodegradation of these mycotoxins by rumen microflora following ingestion of contaminated feeds can lead to their circulatory transport to tissues such as mammary gland as the result of their biodistribution throughout the body. The bovine mammary epithelium plays a pivotal role in maintaining milk yield and composition and contributes to innate immune defense of the udder. The present study is the first to investigate individual effects of OTA and CIT on barrier and innate immune functions of the bovine mammary epithelium using a bovine mammary epithelial cell line (MAC-T). Results indicated that OTA and CIT exposure for 48 h significantly decreased cell viability in a concentration-dependent manner (p < 0.05). A decrease in transepithelial electrical resistance and increase in paracellular flux of FITC-40 kDa dextran was significantly induced by OTA treatment (p < 0.05), but not by CIT after 48 h exposure. qPCR was performed for assessment of expression of tight-junction proteins, Toll-like receptor 4 (TLR4) and cytokines after 4, 24 and 48 h of exposure. Both OTA and CIT markedly downregulated expression of claudin 3 and occludin (p < 0.05), whereas CIT did not affect zonula occludens-1 expression. Expression of TLR4 was significantly upregulated by OTA (p < 0.001) but downregulated by CIT (p < 0.05) at 48 h. Expression of IL-6, TNF-a and TGF-β was significantly upregulated by OTA (p < 0.05), whereas IL-6 and TGF-β expression was downregulated by CIT (p < 0.01). These results suggest that OTA and CIT could potentially differentially modulate barrier and innate immune functions of mammary epithelium. The present study not only throws light on the individual toxicity of each mycotoxin on bovine mammary epithelium but also lays the foundation for future studies on the combined effects of the two mycotoxins. Full article
(This article belongs to the Special Issue Effects of Feedborne Mycotoxins on Animal Health 2.0)
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8 pages, 962 KiB  
Article
Analysis of the Roles of the ISLR2 Gene in Regulating the Toxicity of Zearalenone Exposure in Porcine Intestinal Epithelial Cells
by Zhenbin Bi, Xuezhu Gu, Yeyi Xiao, Yajing Zhou, Wenbin Bao, Shenglong Wu and Haifei Wang
Toxins 2022, 14(9), 639; https://doi.org/10.3390/toxins14090639 - 16 Sep 2022
Cited by 3 | Viewed by 1630
Abstract
Zearalenone (ZEN) is one of the mycotoxins that pose high risks for human and animal health, as well as food safety. However, the regulators involved in ZEN cellular toxicity remain largely unknown. Herein, we showed that cell viability of porcine intestinal epithelial cells [...] Read more.
Zearalenone (ZEN) is one of the mycotoxins that pose high risks for human and animal health, as well as food safety. However, the regulators involved in ZEN cellular toxicity remain largely unknown. Herein, we showed that cell viability of porcine intestinal epithelial cells (IPEC-J2) tended to decrease with increasing doses of ZEN by the cell counting kit-8 assay. Expression of the ISLR2 (immunoglobulin superfamily containing leucine-rich repeat 2) gene in IPEC-J2 cells was significantly downregulated upon ZEN exposure. Furthermore, we found the dose–effect of ZEN on ISLR2 expression. We then overexpressed the ISLR2 gene and observed that overexpression of ISLR2 obviously reduced the effects of ZEN on cell viability, apoptosis rate and oxidative stress level. In addition, ISLR2 overexpression significantly decreased the expression of TNF-α and IFN-α induced by ZEN. Our findings revealed the effects of ZEN on the ISLR2 gene expression and indicated the ISLR2 gene as a novel regulator of ZEN-induced cytotoxicity, which provides potential molecular targets against ZEN toxicity. Full article
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12 pages, 1550 KiB  
Article
Statistical Inferences Applying Non-Parametric Data on Cyanobacterial Investigations: Contributions to Water Quality and New Trends under Global Changes on Portuguese Freshwater Ecosystems
by Cristiana Moreira, Ana Matos, Aldo Barreiro, Cidália Gomes, Vitor Vasconcelos and Agostinho Antunes
Toxins 2022, 14(9), 638; https://doi.org/10.3390/toxins14090638 - 15 Sep 2022
Viewed by 1608
Abstract
Cyanobacteria are a bloom-forming ancient group of photosynthetic prokaryotes. A rise in temperature is a major contributor to its massive proliferation, namely on freshwater ecosystems, with social and economic impacts. Thus, reliable and cost-effective tools can permit the fast surveillance and assessment of [...] Read more.
Cyanobacteria are a bloom-forming ancient group of photosynthetic prokaryotes. A rise in temperature is a major contributor to its massive proliferation, namely on freshwater ecosystems, with social and economic impacts. Thus, reliable and cost-effective tools can permit the fast surveillance and assessment of temperature effects on potentially toxic cyanobacteria distribution and impacts. The occurrence of three potentially toxic cyanobacteria species was assessed on seven sampling points across three sampling years. Moreover, the association between the occurrence of those cyanobacteria species with climate change events was addressed. Here, we combined molecular and statistical methods to study the impacts of temperature on the occurrence of three globally occurring cyanotoxin-producing cyanobacteria species—Microcystis aeruginosa (microcystins), Raphidiopsis raciborskii (cylindrospermopsins and saxitoxins) and Planktothrix agardhii (microcystins and saxitoxins). Samples were collected on seven European temperate freshwater systems located on the North and Centre regions of Portugal, across three distinct sampling years with distinct ranges of air temperature. Data support that M. aeruginosa is still a common inhabitant of Portuguese freshwater ecosystems and a new trend was found on R. raciborskii recent invasion and establishment on the colder north ecosystems of Portugal. Additionally, the highest frequency of detection of both cyanobacteria was associated with warmer years. P. agardhii also revealed a new trend, being reported for the first time on North and Centre Regions of Portugal, however with no statistical relation with air temperature, demonstrating a higher ecological fitness. Distinct profiles of the statistical analysis on the three tested cyanobacteria species contribute to deepen the studies on other species as well as of our analyzed species on a global level. This assessment may help to anticipate possible repercussions on water quality and public health due to most probable alterations on cyanotoxins profile given the ecological fitness established among air temperature and PCR detection of potentially toxic cyanobacteria. Full article
(This article belongs to the Special Issue Cyanobacterial Toxins: Toxins Production and Risk Assessment)
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25 pages, 1399 KiB  
Systematic Review
Serum Calcification Propensity Represents a Good Biomarker of Vascular Calcification: A Systematic Review
by Maxime Pluquet, Said Kamel, Gabriel Choukroun, Sophie Liabeuf and Solène M. Laville
Toxins 2022, 14(9), 637; https://doi.org/10.3390/toxins14090637 - 15 Sep 2022
Cited by 5 | Viewed by 3034
Abstract
Vascular calcification contributes to cardiovascular morbidity and mortality. A recently developed serum calcification propensity assay is based on the half-transformation time (T50) from primary calciprotein particles (CPPs) to secondary CPPs, reflecting the serum’s endogenous capacity to prevent calcium phosphate precipitation. We sought to [...] Read more.
Vascular calcification contributes to cardiovascular morbidity and mortality. A recently developed serum calcification propensity assay is based on the half-transformation time (T50) from primary calciprotein particles (CPPs) to secondary CPPs, reflecting the serum’s endogenous capacity to prevent calcium phosphate precipitation. We sought to identify and review the results of all published studies since the development of the T50-test by Pasch et al. in 2012 (whether performed in vitro, in animals or in the clinic) of serum calcification propensity. To this end, we searched PubMed, Elsevier EMBASE, the Cochrane Library and Google Scholar databases from 2012 onwards. At the end of the selection process, 57 studies were analyzed with regard to the study design, sample size, characteristics of the study population, the intervention and the main results concerning T50. In patients with primary aldosteronism, T50 is associated with the extent of vascular calcification in the abdominal aorta. In chronic kidney disease (CKD), T50 is associated with the severity and progression of coronary artery calcification. T50 is also associated with cardiovascular events and all-cause mortality in CKD patients, patients on dialysis and kidney transplant recipients and with cardiovascular mortality in patients on dialysis, kidney transplant recipients, patients with ischemic heart failure and reduced ejection fraction, and in the general population. Switching from acetate-acidified dialysate to citrate-acidified dialysate led to a longer T50, as did a higher dialysate magnesium concentration. Oral administration of magnesium (in CKD patients), phosphate binders, etelcalcetide and spironolactone (in hemodialysis patients) was associated with a lower serum calcification propensity. Serum calcification propensity is an overall marker of calcification associated with hard outcomes but is currently used in research projects only. This assay might be a valuable tool for screening serum calcification propensity in at-risk populations (such as CKD patients and hemodialyzed patients) and, in particular, for monitoring changes over time in T50. Full article
(This article belongs to the Section Uremic Toxins)
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16 pages, 2298 KiB  
Article
The Origin of Teratogenic Retinoids in Cyanobacteria
by Luděk Sehnal, Marie Smutná, Lucie Bláhová, Pavel Babica, Petra Šplíchalová and Klára Hilscherová
Toxins 2022, 14(9), 636; https://doi.org/10.3390/toxins14090636 - 15 Sep 2022
Cited by 5 | Viewed by 2067
Abstract
Although information about the occurrence and distribution of retinoids in the environment is scarce, cyanobacterial water blooms have been identified as a significant source of these small molecules. Despite the confirmed presence of retinoids in the freshwater blooms dominated by cyanobacteria and their [...] Read more.
Although information about the occurrence and distribution of retinoids in the environment is scarce, cyanobacterial water blooms have been identified as a significant source of these small molecules. Despite the confirmed presence of retinoids in the freshwater blooms dominated by cyanobacteria and their described teratogenic effects, reliable identification of retinoid producers and the mechanism of their biosynthesis is missing. In this study, the cultures of several taxonomically diverse species of axenic cyanobacteria were confirmed as significant producers of retinoid-like compounds. The consequent bioinformatic analysis suggested that the enzymatic background required for the biosynthesis of all-trans retinoic acid from retinal is not present across phylum Cyanobacteria. However, we demonstrated that retinal conversion into other retinoids can be mediated non-enzymatically by free radical oxidation, which leads to the production of retinoids widely detected in cyanobacteria and environmental water blooms, such as all-trans retinoic acid or all-trans 5,6epoxy retinoic acid. Importantly, the production of these metabolites by cyanobacteria in association with the mass development of water blooms can lead to adverse impacts in aquatic ecosystems regarding the described teratogenicity of retinoids. Moreover, our finding that retinal can be non-enzymatically converted into more bioactive retinoids, also in water, and out of the cells, increases the environmental significance of this process. Full article
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18 pages, 5014 KiB  
Article
A Uremic Pig Model for Peritoneal Dialysis
by Joost C. de Vries, Maaike K. van Gelder, Anneke S. Monninkhof, Sabbir Ahmed, Diënty H. M. Hazenbrink, Tri Q. Nguyen, Gèrard A. P. de Kort, Evert-Jan P. A. Vonken, Koen R. D. Vaessen, Jaap A. Joles, Marianne C. Verhaar and Karin G. F. Gerritsen
Toxins 2022, 14(9), 635; https://doi.org/10.3390/toxins14090635 - 14 Sep 2022
Cited by 3 | Viewed by 2226
Abstract
With increasing interest in home dialysis, there is a need for a translational uremic large animal model to evaluate technical innovations in peritoneal dialysis (PD). To this end, we developed a porcine model with kidney failure. Stable chronic kidney injury was induced by [...] Read more.
With increasing interest in home dialysis, there is a need for a translational uremic large animal model to evaluate technical innovations in peritoneal dialysis (PD). To this end, we developed a porcine model with kidney failure. Stable chronic kidney injury was induced by bilateral subtotal renal artery embolization. Before applying PD, temporary aggravation of uremia was induced by administration of gentamicin (10 mg/kg i.v. twice daily for 7 days), to obtain uremic solute levels within the range of those of dialysis patients. Peritoneal transport was assessed using a standard peritoneal permeability assessment (SPA). After embolization, urea and creatinine concentrations transiently increased from 1.6 ± 0.3 to 7.5 ± 1.2 mM and from 103 ± 14 to 338 ± 67 µM, respectively, followed by stabilization within 1–2 weeks to 2.5 ± 1.1 mM and 174 ± 28 µM, respectively. Gentamicin induced temporary acute-on-chronic kidney injury with peak urea and creatinine concentrations of 16.7 ± 5.3 mM and 932 ± 470 µM respectively. PD was successfully applied, although frequently complicated by peritonitis. SPA showed a low transport status (D/P creatinine at 4 h of 0.41 (0.36–0.53)) with a mass transfer area coefficient of 9.6 ± 3.1, 4.6 ± 2.6, 3.4 ± 2.3 mL/min for urea, creatinine, and phosphate respectively. In conclusion, this porcine model with on-demand aggravation of uremia is suitable for PD albeit with peritoneal transport characterized by a low transport status. Full article
(This article belongs to the Special Issue Analysis and Applications of Uremic Animal Models)
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18 pages, 1341 KiB  
Article
Analysis and Comparison of Rapid Methods for the Determination of Ochratoxin a Levels in Organs and Body Fluids Obtained from Exposed Mice
by Zsuzsanna Szőke, Bianka Babarczi, Miklós Mézes, István Lakatos, Miklós Poór, Eszter Fliszár-Nyúl, Miklós Oldal, Árpád Czéh, Kornélia Bodó, György Nagyéri and Szilamér Ferenczi
Toxins 2022, 14(9), 634; https://doi.org/10.3390/toxins14090634 - 13 Sep 2022
Cited by 5 | Viewed by 2290
Abstract
Mycotoxins are bioaccumulative contaminants impacting animals and humans. The simultaneous detection of frequent active exposures and accumulated mycotoxin level (s) in exposed organisms would be the most ideal to enable appropriate actions. However, few methods are available for the purpose, and there is [...] Read more.
Mycotoxins are bioaccumulative contaminants impacting animals and humans. The simultaneous detection of frequent active exposures and accumulated mycotoxin level (s) in exposed organisms would be the most ideal to enable appropriate actions. However, few methods are available for the purpose, and there is a demand for dedicated, sensitive, reliable, and practical assays. To demonstrate the issue, mice were exposed to a relevant agent Ochratoxin A (OTA), and accumulated OTA was measured by fine-tuned commercial assays. Quantitative high-performance liquid chromatography with fluorescence detection, enzyme-linked immunosorbent assay, and flow cytometry assays have been developed/modified using reagents available as commercial products when appropriate. Assays were performed on excised samples, and results were compared. Accumulated OTA could be detected and quantified; positive correlations (between applied doses of exposure and accumulated OTA levels and the results from assays) were found. Dedicated assays could be developed, which provided comparable results. The presence and accumulation of OTA following even a short exposure could be quantitatively detected. The assays performed similarly, but HPLC had the greatest sensitivity. Blood contained higher levels of OTA than liver and kidney. We demonstrate that specific but flexible and practical assays should be used for specific/local purposes, to measure the exposure itself and accumulation in blood or organs. Full article
(This article belongs to the Special Issue Occurrence and Determination of Mycotoxins)
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19 pages, 6082 KiB  
Article
Combined Hepatotoxicity and Toxicity Mechanism of Intermedine and Lycopsamine
by Ziqi Wang, Liang Qiao, Qinqin Zheng, Haolei Han, Zuguang Li, Xiangchun Zhang and Hongping Chen
Toxins 2022, 14(9), 633; https://doi.org/10.3390/toxins14090633 - 13 Sep 2022
Cited by 4 | Viewed by 2010
Abstract
Pyrrolizidine alkaloids (PAs) are common constituents of plants and have serious hepatotoxicity. Intermedine (Im) and lycopsamine (La) are two monoesters of PAs that frequently coexist in the PA-containing plants (e.g., comfrey and tea). The present study aimed to explore the combined hepatotoxicity and [...] Read more.
Pyrrolizidine alkaloids (PAs) are common constituents of plants and have serious hepatotoxicity. Intermedine (Im) and lycopsamine (La) are two monoesters of PAs that frequently coexist in the PA-containing plants (e.g., comfrey and tea). The present study aimed to explore the combined hepatotoxicity and toxicity mechanism of the Im and La mixture. In vitro, the combined cytotoxicity of the Im and La mixture on human hepatocytes (HepD) was examined by CCK-8, colony formation, wound healing, and Annexin V/PI staining assays. The combination of Im and La inhibited the ability of HepD cells to proliferate, colonize, and migrate and induced hepatocytes apoptosis in a dose-dependent manner. In addition to significantly causing a burst of intracellular reactive oxygen species (ROS), mitochondrial apoptosis, and endoplasmic reticulum (ER) stress, the Im and La mixture can also cause an increase in intracellular Ca2+, triggering the PERK/eIF2α/ATF4/CHOP apoptosis pathway. This study provided the first direct evidence that the combined PAs induced hepatotoxicity through ER-mediated apoptosis. These results supplemented the basic toxicity data for the combined PAs and provided a new perspective for the risk assessment of combined PA toxicity. Full article
(This article belongs to the Special Issue Toxicity and Therapeutic Potential of Plant Alkaloid)
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29 pages, 9164 KiB  
Review
Recent Advances on Biological Activities and Structural Modifications of Dehydroabietic Acid
by Meng Hao, Jianwei Xu, Houpeng Wen, Jiawei Du, Shaoyong Zhang, Min Lv and Hui Xu
Toxins 2022, 14(9), 632; https://doi.org/10.3390/toxins14090632 - 12 Sep 2022
Cited by 12 | Viewed by 2681
Abstract
Dehydroabietic acid is a tricyclic diterpenoid resin acid isolated from rosin. Dehydroabietic acid and its derivatives showed lots of medical and agricultural bioactivities, such as anticancer, antibacterial, antiviral, antiulcer, insecticidal, and herbicidal activities. This review summarized the research advances on the structural modification [...] Read more.
Dehydroabietic acid is a tricyclic diterpenoid resin acid isolated from rosin. Dehydroabietic acid and its derivatives showed lots of medical and agricultural bioactivities, such as anticancer, antibacterial, antiviral, antiulcer, insecticidal, and herbicidal activities. This review summarized the research advances on the structural modification and total synthesis of dehydroabietic acid and its derivatives from 2015 to 2021, and analyzed the biotransformation and structure-activity relationships in order to provide a reference for the development and utilization of dehydroabietic acid and its derivatives as drugs and pesticides. Full article
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16 pages, 1575 KiB  
Article
Immunoaffinity Cleanup and Isotope Dilution-Based Liquid Chromatography Tandem Mass Spectrometry for the Determination of Six Major Mycotoxins in Feed and Feedstuff
by Ying Liu, Yongpeng Jin, Qi Guo, Xiong Wang, Sunlin Luo, Wenjun Yang, Juntao Li and Yiqiang Chen
Toxins 2022, 14(9), 631; https://doi.org/10.3390/toxins14090631 - 11 Sep 2022
Cited by 3 | Viewed by 1723
Abstract
In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of deoxynivalenol, aflatoxin B1, zearalenone, ochratoxin A, T-2 toxin and fumonisin B1 in feed and feedstuff was established. The sample was extracted with an acetonitrile–water mixture (60:40, [...] Read more.
In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of deoxynivalenol, aflatoxin B1, zearalenone, ochratoxin A, T-2 toxin and fumonisin B1 in feed and feedstuff was established. The sample was extracted with an acetonitrile–water mixture (60:40, v/v), purified by an immunoaffinity column, eluted with a methanol–acetic acid mixture (98:2, v/v), and reconstituted with a methanol–water mixture (50:50, v/v) after drying with nitrogen. Finally, the reconstituted solution was detected by LC-MS/MS and quantified by isotope internal standard method. The six mycotoxins had a good linear relationship in a certain concentration range, the correlation coefficients were all greater than 0.99, the limits of detection were between 0.075 and 1.5 µg·kg−1, and the limits of quantification were between 0.5 and 5 µg·kg−1. The average spike recoveries in the four feed matrices ranged from 84.2% to 117.1% with relative standard deviations less than 11.6%. Thirty-six actual feed samples were analyzed for mycotoxins, and at least one mycotoxin was detected in each sample. The proposed method is reliable and suitable for detecting common mycotoxins in feed samples. Full article
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23 pages, 6542 KiB  
Article
Transcriptome Sequencing and Comparison of Venom Glands Revealed Intraspecific Differentiation and Expression Characteristics of Toxin and Defensin Genes in Mesobuthus martensii Populations
by Zhiyong Di, Sha Qiao, Xiaoshuang Liu, Shuqing Xiao, Cheng Lei, Yonghao Li, Shaobin Li and Feng Zhang
Toxins 2022, 14(9), 630; https://doi.org/10.3390/toxins14090630 - 11 Sep 2022
Cited by 1 | Viewed by 1754
Abstract
Mesobuthus martensii, a famous and important Traditional Chinese Medicine has a long medical history and unique functions. It is the first scorpion species whose whole genome was sequenced worldwide. In addition, it is the most widespread and infamous poisonous animal in northern [...] Read more.
Mesobuthus martensii, a famous and important Traditional Chinese Medicine has a long medical history and unique functions. It is the first scorpion species whose whole genome was sequenced worldwide. In addition, it is the most widespread and infamous poisonous animal in northern China with complex habitats. It possesses several kinds of toxins that can regulate different ion channels and serve as crucial natural drug resources. Extensive and in-depth studies have been performed on the structures and functions of toxins of M. martensii. In this research, we compared the morphology of M. martensii populations from different localities and calculated the COI genetic distance to determine intraspecific variations. Transcriptome sequencing by RNA-sequencing of the venom glands of M. martensii from ten localities and M. eupeus from one locality was analyzed. The results revealed intraspecific variation in the expression of sodium channel toxin genes, potassium channel toxin genes, calcium channel toxin genes, chloride channel toxin genes, and defensin genes that could be related to the habitats in which these populations are distributed, except the genetic relationships. However, it is not the same in different toxin families. M. martensii and M. eupeus exhibit sexual dimorphism under the expression of toxin genes, which also vary in different toxin families. The following order was recorded in the difference of expression of sodium channel toxin genes: interspecific difference; differences among different populations of the same species; differences between sexes in the same population, whereas the order in the difference of expression of potassium channel toxin genes was interspecific difference; differences between both sexes of same populations; differences among the same sex in different populations of the same species. In addition, there existed fewer expressed genes of calcium channel toxins, chloride channel toxins, and defensins (no more than four members in each family), and their expression differences were not distinct. Interestingly, the expression of two calcium channel toxin genes showed a preference for males and certain populations. We found a difference in the expression of sodium channel toxin genes, potassium channel toxin genes, and chloride channel toxin genes between M. martensii and M. eupeus. In most cases, the expression of one member of the toxin gene clusters distributed in series on the genome were close in different populations and genders, and the members of most clusters expressed in same population and gender tended to be the different. Twenty-one toxin genes were found with the MS/MS identification evidence of M. martensii venom. Since scorpions were not subjected to electrical stimulation or other special treatments before conducting the transcriptome extraction experiment, the results suggested the presence of intraspecific variation and sexual dimorphism of toxin components which revealed the expression characteristics of toxin and defensin genes in M. martensii. We believe this study will promote further in-depth research and use of scorpions and their toxin resources, which in turn will be helpful in standardizing the identification and medical applications of Quanxie in traditional Chinese medicine. Full article
(This article belongs to the Special Issue Advanced Research on Animal Venoms in China)
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36 pages, 33616 KiB  
Review
Towards Understanding the Function of Aegerolysins
by Nada Kraševec and Matej Skočaj
Toxins 2022, 14(9), 629; https://doi.org/10.3390/toxins14090629 - 11 Sep 2022
Cited by 6 | Viewed by 2077
Abstract
Aegerolysins are remarkable proteins. They are distributed over the tree of life, being relatively widespread in bacteria and fungi, but also present in some insects, plants, protozoa, and viruses. Despite their abundance in cells of certain developmental stages and their presence in secretomes, [...] Read more.
Aegerolysins are remarkable proteins. They are distributed over the tree of life, being relatively widespread in bacteria and fungi, but also present in some insects, plants, protozoa, and viruses. Despite their abundance in cells of certain developmental stages and their presence in secretomes, only a few aegerolysins have been studied in detail. Their function, in particular, is intriguing. Here, we summarize previously published findings on the distribution, molecular interactions, and function of these versatile aegerolysins. They have very diverse protein sequences but a common fold. The machine learning approach of the AlphaFold2 algorithm, which incorporates physical and biological knowledge of protein structures and multisequence alignments, provides us new insights into the aegerolysins and their pore-forming partners, complemented by additional genomic support. We hypothesize that aegerolysins are involved in the mechanisms of competitive exclusion in the niche. Full article
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16 pages, 7119 KiB  
Article
Protective Effect of SeMet on Liver Injury Induced by Ochratoxin A in Rabbits
by Ziqiang Zhang, Jingyi Xu, Xin Zhang, Jiajia Wang, Hui Xie, Yingying Sun, Qianwen Zhang, Zhaoyang Chang and Yumei Liu
Toxins 2022, 14(9), 628; https://doi.org/10.3390/toxins14090628 - 8 Sep 2022
Cited by 9 | Viewed by 2171
Abstract
Ochratoxin A (OTA) is second only to aflatoxin in toxicity among mycotoxins. Recent studies have shown that selenomethionine (SeMet) has a protective effect on mycotoxin-induced toxicity. The purpose of this study was to investigate the protective effect and mechanism of SeMet on OTA-induced [...] Read more.
Ochratoxin A (OTA) is second only to aflatoxin in toxicity among mycotoxins. Recent studies have shown that selenomethionine (SeMet) has a protective effect on mycotoxin-induced toxicity. The purpose of this study was to investigate the protective effect and mechanism of SeMet on OTA-induced liver injury in rabbits. Sixty 35-day-old rabbits with similar body weight were randomly divided into five groups: control group, OTA group (0.2 mg/kg OTA), OTA + 0.2 mg/kg SeMet group, OTA + 0.4 mg/kg SeMet group and OTA + 0.6 mg/kg SeMet group. Rabbits were fed different doses of the SeMet diet for 21 d, and OTA was administered for one week from day 15 (the control group was provided the same dose of NaHCO3 solution). The results showed that 0.4 mg/kg SeMet could significantly improve the liver injury induced by OTA poisoning. SeMet supplementation can improve the changes in physiological blood indexes caused by OTA poisoning in rabbits and alleviate pathological damage to the rabbit liver. SeMet also increased the activities of SOD, GSH-Px and T-AOC and significantly decreased the contents of ROS, MDA, IL-1β, IL-6 and TNF-α, effectively alleviating the oxidative stress and inflammatory response caused by OTA poisoning. In addition, OTA poisoning inhibits Nrf2 and HO-1 levels, ultimately leading to peroxide reaction, while SeMet activates the Nrf2 signaling pathway and enhances the expression of the HO-1 downstream Nrf2 gene. These results suggest that Se protects the liver from OTA-induced hepatotoxicity by regulating Nrf2/HO-1 expression. Full article
(This article belongs to the Section Mycotoxins)
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14 pages, 1552 KiB  
Article
Deoxynivalenol and T-2 Toxin as Major Concerns in Durum Wheat from Italy
by Miriam Haidukowski, Stefania Somma, Veronica Ghionna, Maria Teresa Cimmarusti, Mario Masiello, Antonio Francesco Logrieco and Antonio Moretti
Toxins 2022, 14(9), 627; https://doi.org/10.3390/toxins14090627 - 8 Sep 2022
Cited by 10 | Viewed by 1894
Abstract
Fusarium Head Blight is a devastating disease of wheat caused by a complex of Fusarium species producing a wide range of mycotoxins. Fusarium species occurrence is variable in different geographical areas and subjected to a continuous evolution in their distribution. A total of [...] Read more.
Fusarium Head Blight is a devastating disease of wheat caused by a complex of Fusarium species producing a wide range of mycotoxins. Fusarium species occurrence is variable in different geographical areas and subjected to a continuous evolution in their distribution. A total of 141 durum wheat field samples were collected in different regions of Italy in three years, and analyzed for Fusarium species and related mycotoxin occurrence. Mycotoxin contamination varied according to year and geographical origin. The highest mycotoxin contamination was detected in 2014. Deoxynivalenol was detected with an average of 240 µg/kg only in Central and Northern Italy; and T-2 and HT-2 toxins with an average of 150 µg/kg in Southern Italy. Approximately 80% of samples from Southern Italy in 2013/2014 showed T-2 and HT-2 levels over the EU recommended limits. Fusarium graminearum occurred mostly in Northern Italy, while F. langsethiae occurred in Southern Italy. These data showed that a real mycotoxin risk related to Fusarium exists on the whole in Italy, but varies according with geographical areas and environmental conditions. Consistent monitoring of Fusarium species and related mycotoxin distribution on a long period is worthwhile to generate more accurate knowledge on Fusarium species profile and mycotoxins associated and better establish the climatic change impact on wheat Fusarium epidemiology. Full article
(This article belongs to the Section Mycotoxins)
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14 pages, 822 KiB  
Review
Gut–Kidney Axis Investigations in Animal Models of Chronic Kidney Disease
by Piotr Bartochowski, Nathalie Gayrard, Stéphanie Bornes, Céline Druart, Angel Argilés, Magali Cordaillat-Simmons and Flore Duranton
Toxins 2022, 14(9), 626; https://doi.org/10.3390/toxins14090626 - 7 Sep 2022
Cited by 6 | Viewed by 3576
Abstract
Chronic kidney disease (CKD) is an incurable disease in which renal function gradually declines, resulting in no noticeable symptoms during the early stages and a life-threatening disorder in the latest stage. The changes that accompany renal failure are likely to influence the gut [...] Read more.
Chronic kidney disease (CKD) is an incurable disease in which renal function gradually declines, resulting in no noticeable symptoms during the early stages and a life-threatening disorder in the latest stage. The changes that accompany renal failure are likely to influence the gut microbiota, or the ecosystem of micro-organisms resident in the intestine. Altered gut microbiota can display metabolic changes and become harmful to the host. To study the gut–kidney axis in vivo, animal models should ideally reproduce the disorders affecting both the host and the gut microbiota. Murine models of CKD, but not dog, manifest slowed gut transit, similarly to patient. Animal models of CKD also reproduce altered intestinal barrier function, as well as the resulting leaky gut syndrome and bacterial translocation. CKD animal models replicate metabolic but not compositional changes in the gut microbiota. Researchers investigating the gut–kidney axis should pay attention to the selection of the animal model (disease induction method, species) and the setting of the experimental design (control group, sterilization method, individually ventilated cages) that have been shown to influence gut microbiota. Full article
(This article belongs to the Special Issue Kidney Disease-Gut Dysbiosis: What Is the Role of Uremic Toxins?)
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10 pages, 1153 KiB  
Article
Examination of Microcystin Adsorption by the Type of Plastic Materials Used during the Procedure of Microcystin Analysis
by Chan Seo, Joo Won Lee, Won-Kyo Jung, Yoon-Mi Lee, Seungjun Lee and Sang Gil Lee
Toxins 2022, 14(9), 625; https://doi.org/10.3390/toxins14090625 - 7 Sep 2022
Cited by 5 | Viewed by 1997
Abstract
The incidence of eutrophication is increasing due to fertilizer abuse and global warming. Eutrophication can induce the proliferation of cyanobacteria such as Microcystis, which produces microcystins. Microcystins are toxic to specific organs such as the liver and the heart. Thus, monitoring of [...] Read more.
The incidence of eutrophication is increasing due to fertilizer abuse and global warming. Eutrophication can induce the proliferation of cyanobacteria such as Microcystis, which produces microcystins. Microcystins are toxic to specific organs such as the liver and the heart. Thus, monitoring of microcystins is strongly required to control drinking water and agricultural product qualities. However, microcystins could be adsorbed by plastic materials during sample storage and preparation, hindering accurate analysis. Therefore, the current study examined the recovery rate of microcystins from six plastics used for containers and eight plastics used for membrane filters. Among the six plastics used for containers, polyethylene terephthalate showed the best recovery rate (≥81.3%) for 48 h. However, polypropylene, polystyrene, and high- and low-density polyethylenes showed significant adsorption after exposure for 1 hr. For membrane materials, regenerated cellulose (≥99.3%) showed the highest recovery rate of microcystins, followed by polyvinylidene fluoride (≥94.1%) and polytetrafluoroethylene (≥95.7%). The adsorption of microcystins appeared to be strongly influenced by various molecular interactions, including hydrophobic interaction, hydrogen bonding, and electrostatic interaction. In addition, microcystins’ functional residues seemed to be critical factors affecting their adsorption by plastic materials. The present study demonstrates that polyethylene terephthalate and regenerated cellulose membrane are suitable plastic materials for the analysis of microcystins. Full article
(This article belongs to the Special Issue Recent Advances in Microcystins)
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13 pages, 4986 KiB  
Article
The Neurotoxic Effect of Ochratoxin-A on the Hippocampal Neurogenic Niche of Adult Mouse Brain
by Eva Mateo, Rik Paulus Bernardus Tonino, Antolin Canto, Antonio Monroy Noyola, Maria Miranda, Jose Miguel Soria and María Angeles Garcia Esparza
Toxins 2022, 14(9), 624; https://doi.org/10.3390/toxins14090624 - 6 Sep 2022
Cited by 3 | Viewed by 2016
Abstract
Ochratoxin A (OTA) is a common secondary metabolite of Aspergillus ochraceus, A. carbonarius, and Penicillium verrucosum. This mycotoxin is largely present as a contaminant in several cereal crops and human foodstuffs, including grapes, corn, nuts, and figs, among others. Preclinical [...] Read more.
Ochratoxin A (OTA) is a common secondary metabolite of Aspergillus ochraceus, A. carbonarius, and Penicillium verrucosum. This mycotoxin is largely present as a contaminant in several cereal crops and human foodstuffs, including grapes, corn, nuts, and figs, among others. Preclinical studies have reported the involvement of OTA in metabolic, physiologic, and immunologic disturbances as well as in carcinogenesis. More recently, it has also been suggested that OTA may impair hippocampal neurogenesis in vivo and that this might be associated with learning and memory deficits. Furthermore, aside from its widely proven toxicity in tissues other than the brain, there is reason to believe that OTA contributes to neurodegenerative disorders. Thus, in this present in vivo study, we investigated this possibility by intraperitoneally (i.p.) administering 3.5 mg OTA/kg body weight to adult male mice to assess whether chronic exposure to this mycotoxin negatively affects cell viability in the dentate gyrus of the hippocampus. Immunohistochemistry assays showed that doses of 3.5 mg/kg caused a significant and dose-dependent reduction in repetitive cell division and branching (from 12% to 62%). Moreover, the number of countable astrocytes (p < 0.001), young neurons (p < 0.001), and mature neurons (p < 0.001) negatively correlated with the number of i.p. OTA injections administered (one, two, three, or six repeated doses). Our results show that OTA induced adverse effects in the hippocampus cells of adult mice brain tissue when administered in cumulative doses. Full article
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17 pages, 2114 KiB  
Review
Postbiotics and Kidney Disease
by Chiara Favero, Laura Giordano, Silvia Maria Mihaila, Rosalinde Masereeuw, Alberto Ortiz and Maria Dolores Sanchez-Niño
Toxins 2022, 14(9), 623; https://doi.org/10.3390/toxins14090623 - 6 Sep 2022
Cited by 5 | Viewed by 5838
Abstract
Chronic kidney disease (CKD) is projected to become the fifth global cause of death by 2040 as a result of key shortcomings in the current methods available to diagnose and treat kidney diseases. In this regard, the novel holobiont concept, used to describe [...] Read more.
Chronic kidney disease (CKD) is projected to become the fifth global cause of death by 2040 as a result of key shortcomings in the current methods available to diagnose and treat kidney diseases. In this regard, the novel holobiont concept, used to describe an individual host and its microbial community, may pave the way towards a better understanding of kidney disease pathogenesis and progression. Microbiota-modulating or -derived interventions include probiotics, prebiotics, synbiotics and postbiotics. As of 2019, the concept of postbiotics was updated by the International Scientific Association of Probiotics and Prebiotics (ISAPP) to refer to preparations of inanimate microorganisms and/or their components that confer a health benefit to the host. By explicitly excluding purified metabolites without a cellular biomass, any literature making use of such term is potentially rendered obsolete. We now review the revised concept of postbiotics concerning their potential clinical applications and research in kidney disease, by discussing in detail several formulations that are undergoing preclinical development such as GABA-salt for diet-induced hypertension and kidney injury, sonicated Lactobacillus paracasei in high fat diet-induced kidney injury, GABA-salt, lacto-GABA-salt and postbiotic-GABA-salt in acute kidney injury, and O. formigenes lysates for hyperoxaluria. Furthermore, we provide a roadmap for postbiotics research in kidney disease to expedite clinical translation. Full article
(This article belongs to the Special Issue Kidney Disease-Gut Dysbiosis: What Is the Role of Uremic Toxins?)
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15 pages, 2006 KiB  
Article
Optimization of Gonyautoxin1/4-Binding G-Quadruplex Aptamers by Label-Free Surface-Enhanced Raman Spectroscopy
by Yan Liu, Chengshun Jiang, Menghua Song, Yongbing Cao, Qiang Huang and Feng Lu
Toxins 2022, 14(9), 622; https://doi.org/10.3390/toxins14090622 - 6 Sep 2022
Cited by 1 | Viewed by 1632
Abstract
Nucleic acids with G-quadruplex (G4) structures play an important role in physiological function, analysis and detection, clinical diagnosis and treatment, and new drug research and development. Aptamers obtained using systematic evolution of ligands via exponential enrichment (SELEX) screening technology do not always have [...] Read more.
Nucleic acids with G-quadruplex (G4) structures play an important role in physiological function, analysis and detection, clinical diagnosis and treatment, and new drug research and development. Aptamers obtained using systematic evolution of ligands via exponential enrichment (SELEX) screening technology do not always have the best affinity or binding specificity to ligands. Therefore, the establishment of a structure-oriented experimental method is of great significance. To study the potential of surface-enhanced Raman spectroscopy (SERS) in aptamer optimization, marine biotoxin gonyautoxin (GTX)1/4 and its G4 aptamer obtained using SELEX were selected. The binding site and the induced fit of the aptamer to GTX1/4 were confirmed using SERS combined with two-dimensional correlation spectroscopy. The intensity of interaction between GTX1/4 and G4 was also quantified by measuring the relative intensity of SERS bands corresponding to intramolecular hydrogen bonds. Furthermore, the interaction between GTX1/4 and optimized aptamers was analyzed. The order of intensity change in the characteristic bands of G4 aptamers was consistent with the order of affinity calculated using microscale thermophoresis and molecular dynamics simulations. SERS provides a rapid, sensitive, and economical post-SELEX optimization of aptamers. It is also a reference for future research on other nucleic acid sequences containing G4 structures. Full article
(This article belongs to the Section Marine and Freshwater Toxins)
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10 pages, 1085 KiB  
Article
Atropine and Scopolamine in Maize Products from the Retail Stores in the Republic of Serbia
by Gorica Vuković, Tijana Stojanović, Bojan Konstantinović, Vojislava Bursić, Nikola Puvača, Milena Popov, Nataša Samardžić, Aleksandra Petrović, Dušan Marinković, Svetlana Roljević Nikolić, Rada Đurović Pejčev and Bojana Špirović Trifunović
Toxins 2022, 14(9), 621; https://doi.org/10.3390/toxins14090621 - 5 Sep 2022
Cited by 6 | Viewed by 2178
Abstract
The cereal grains, which represent the cultivated grasses fruits, supply almost half of the total caloric requirements for humans and provide more nourishment compared with any other class of the food. Out of many cereals used for food, maize, rice, and wheat are [...] Read more.
The cereal grains, which represent the cultivated grasses fruits, supply almost half of the total caloric requirements for humans and provide more nourishment compared with any other class of the food. Out of many cereals used for food, maize, rice, and wheat are the most important food resources for humans, representing 94% of the total cereals consumption. According to the data of the Republic Institute of Statistics for the year 2018, the harvested areas of corn amount to 906,753 hectares. The production of about 7 million tons was achieved with an average yield of 7.7 t/ha according to the Ministry of Agriculture of the Republic of Serbia. Serbia is still among the ten largest exporters of wheat and corn in the world for the period of 2014/15–2017/18. More precisely, it ranks seventh in the export of corn. Utilization of maize products for food animal nutrition (1000 t) is 491,48, and for industrial processing (1000 t) 278,862 expressed as the total consumption (1000 t) is 769,910. Therefore, a total of 103 samples of maize products were analyzed for the presence of toxins, i.e., tropane alkaloids (TAs). The samples were collected from the retail stores in the Republic of Serbia in 2021 and analyzed for the presence of atropine and scopolamine (33 corn grits, 39 polenta, and 31 semolina samples). Therefore, the Recommendation 2015/976/EU on the monitoring of TAs in food was adopted by the EU Commission to obtain more occurrence data on TAs in food. The monitoring extent, however, is restricted because reliable analytical methods and appropriate sensitivity are limited. There was a limit of 1 g/kg for each atropine and scopolamine in cereals containing millet, sorghum, buckwheat, or their derivatives. All the samples were analyzed by the LC-MS/MS. The LOQ was set at 1.0 μg/kg. Out of the total 103 tested samples, 32 samples (31.1%) were contaminated with atropine and scopolamine in concentrations above the LOQ. The highest concentrations of the studied TAs were observed in a semolina sample-atropine: 58.80 μg/kg, scopolamine: 10.20 μg/kg. The obtained results indicate that the TAs concentrations are above the LOQ which can be considered potential human and animal health hazards. Full article
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15 pages, 1371 KiB  
Article
Influence of Agronomic Factors on Mycotoxin Contamination in Maize and Changes during a 10-Day Harvest-Till-Drying Simulation Period: A Different Perspective
by Bernat Borràs-Vallverdú, Antonio J. Ramos, Carlos Cantero-Martínez, Sonia Marín, Vicente Sanchis and Jesús Fernández-Ortega
Toxins 2022, 14(9), 620; https://doi.org/10.3390/toxins14090620 - 5 Sep 2022
Cited by 8 | Viewed by 1726
Abstract
Agronomic factors can affect mycotoxin contamination of maize, one of the most produced cereals. Maize is usually harvested at 18% moisture, but it is not microbiologically stable until it reaches 14% moisture at the drying plants. We studied how three agronomic factors (crop [...] Read more.
Agronomic factors can affect mycotoxin contamination of maize, one of the most produced cereals. Maize is usually harvested at 18% moisture, but it is not microbiologically stable until it reaches 14% moisture at the drying plants. We studied how three agronomic factors (crop diversification, tillage system and nitrogen fertilization rate) can affect fungal and mycotoxin contamination (deoxynivalenol and fumonisins B1 and B2) in maize at harvest. In addition, changes in maize during a simulated harvest-till-drying period were studied. DON content at harvest was higher for maize under intensive tillage than using direct drilling (2695 and 474 μg kg−1, respectively). We found two reasons for this: (i) soil crusting in intensive tillage plots caused the formation of pools of water that created high air humidity conditions, favouring the development of DON-producing moulds; (ii) the population of Lumbricus terrestris, an earthworm that would indirectly minimize fungal infection and mycotoxin production on maize kernels, is reduced in intensive tillage plots. Therefore, direct drilling is a better approach than intensive tillage for both preventing DON contamination and preserving soil quality. Concerning the simulated harvest-till-drying period, DON significantly increased between storage days 0 and 5. Water activity dropped on the 4th day, below the threshold for DON production (around 0.91). From our perspective, this study constitutes a step forward towards understanding the relationships between agronomic factors and mycotoxin contamination in maize, and towards improving food safety. Full article
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8 pages, 1830 KiB  
Review
Botulinum Toxin—A Current Place in the Treatment of Chronic Migraine and Other Primary Headaches
by Katarzyna Kępczyńska and Izabela Domitrz
Toxins 2022, 14(9), 619; https://doi.org/10.3390/toxins14090619 - 5 Sep 2022
Cited by 8 | Viewed by 7402
Abstract
Headaches are a very common condition that most people will experience many times during their lives. This article presents the primary headaches, which are a large group of diseases where the headache is not a symptom of another known disease. Tension-type headache affects [...] Read more.
Headaches are a very common condition that most people will experience many times during their lives. This article presents the primary headaches, which are a large group of diseases where the headache is not a symptom of another known disease. Tension-type headache affects approximately 80% of the general population, and the prevalence of migraine is estimated at 10–12%. Clinical data and experience to date have demonstrated that botulinum toxin may be an effective prophylactic treatment for chronic headache types. It has been used in neurology for the treatment of dystonia and blepharospasm. Now it has been approved to treat chronic migraine and has been shown to confer significant benefit in refractory cases. Based on clinical experience botulinum toxin has also been tried in other headache disorders. While it is intuitively attractive to think that due to its effect on pain by sensory modulation, there may also be efficacy in its use in chronic tension-type headache and cluster headache, so far, there is little evidence to support this. Botulinum toxin is effective in pain control through its interaction with the SNARE complex, which inhibits the release of neurotransmitters, such as glutamate, substance P and calcitonin gene-related peptide. OnabotulinumtoxinA is effective not only in headache frequency and pain intensity but in other parameters, including quality of life. Full article
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17 pages, 11713 KiB  
Article
Drivers of Post-Harvest Aflatoxin Contamination: Evidence Gathered from Knowledge Disparities and Field Surveys of Maize Farmers in the Rift Valley Region of Kenya
by Grace Gachara, Rashid Suleiman, Sara El Kadili, Essaid Ait Barka, Beatrice Kilima and Rachid Lahlali
Toxins 2022, 14(9), 618; https://doi.org/10.3390/toxins14090618 - 3 Sep 2022
Cited by 2 | Viewed by 2074
Abstract
Maize-dependent populations in sub-Saharan Africa are continually exposed to aflatoxin poisoning owing to their regular consumption of this dietetic cereal. Being a staple in Kenyan households, consumption of maize-based meals is done almost daily, thereby exposing consumers to aflatoxicoses. This study assessed awareness [...] Read more.
Maize-dependent populations in sub-Saharan Africa are continually exposed to aflatoxin poisoning owing to their regular consumption of this dietetic cereal. Being a staple in Kenyan households, consumption of maize-based meals is done almost daily, thereby exposing consumers to aflatoxicoses. This study assessed awareness levels, knowledge disparities, and perceptions regarding aflatoxin contamination at the post-harvest phase among farmers in the Rift Valley Region of Kenya. Households were randomly selected using a geographical positioning system (GPS) overlay of the agro-ecological zones within Uasin Gishu and Elgeyo Marakwet counties. Face-to-face interviews were conducted in 212 smallholder and large-scale farms. The study documented the demographic profiles of farmers and knowledge, awareness, and perceptions of aflatoxin contamination using a pre-designed structured questionnaire. Most farmers were familiar with aflatoxins and the adverse effects they present to health (61.32%). Almost all the farmers (94.37%) were aware of storage molds and food-spoilage fungi. However, few farmers adopted good post-harvest practices (PHPs), such as avoiding premature harvests (49.8%), using well-ventilated storage spaces (44.6%), grain sorting (30.5%), proper drying of maize (17.8%), and using hermetic bags for storage (30.5%). Conclusively, intensified farmer education is required to train farmers on good PHPs to protect their maize from aflatoxigenic fungi and aflatoxin accumulation. Full article
(This article belongs to the Section Mycotoxins)
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