Toxins

27 pages, 1220 KiB

Open AccessEditor’s ChoiceArticle

In Silico and In Vitro Studies of Mycotoxins and Their Cocktails; Their Toxicity and Its Mitigation by Silibinin Pre-Treatment

by Van Nguyen Tran, Jitka Viktorova, Katerina Augustynkova, Nikola Jelenova, Simona Dobiasova, Katerina Rehorova, Marie Fenclova, Milena Stranska-Zachariasova, Libor Vitek, Jana Hajslova and Tomas Ruml

Toxins 2020, 12(3), 148; https://doi.org/10.3390/toxins12030148 - 28 Feb 2020

Cited by 39 | Viewed by 5898

Abstract

Mycotoxins found in randomly selected commercial milk thistle dietary supplement were evaluated for their toxicity in silico and in vitro. Using in silico methods, the basic physicochemical, pharmacological, and toxicological properties of the mycotoxins were predicted using ACD/Percepta. The in vitro cytotoxicity of [...] Read more.

Mycotoxins found in randomly selected commercial milk thistle dietary supplement were evaluated for their toxicity in silico and in vitro. Using in silico methods, the basic physicochemical, pharmacological, and toxicological properties of the mycotoxins were predicted using ACD/Percepta. The in vitro cytotoxicity of individual mycotoxins was determined in mouse macrophage (RAW 264.7), human hepatoblastoma (HepG2), and human embryonic kidney (HEK 293T) cells. In addition, we studied the bioavailability potential of mycotoxins and silibinin utilizing an in vitro transwell system with differentiated human colon adenocarcinoma cells (Caco-2) simulating mycotoxin transfer through the intestinal epithelial barrier. The IC₅₀ values for individual mycotoxins in studied cells were in the biologically relevant ranges as follows: 3.57–13.37 nM (T-2 toxin), 5.07–47.44 nM (HT-2 toxin), 3.66–17.74 nM (diacetoxyscirpenol). Furthermore, no acute toxicity was obtained for deoxynivalenol, beauvericin, zearalenone, enniatinENN-A, enniatin-A1, enniatin-B, enniatin-B1, alternariol, alternariol-9-methyl ether, tentoxin, and mycophenolic acid up to the 50 nM concentration. The acute toxicity of these mycotoxins in binary combinations exhibited antagonistic effects in the combinations of T-2 with DON, ENN-A1, or ENN-B, while the rest showed synergistic or additive effects. Silibinin had a significant protective effect against both the cytotoxicity of three mycotoxins (T-2 toxin, HT-2 toxin, DAS) and genotoxicity of AME, AOH, DON, and ENNs on HEK 293T. The bioavailability results confirmed that AME, DAS, ENN-B, TEN, T-2, and silibinin are transported through the epithelial cell layer and further metabolized. The bioavailability of silibinin is very similar to mycotoxins poor penetration. Full article

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

► Show Figures

Figure 1

19 pages, 388 KiB

Open AccessEditor’s ChoiceArticle

Variation of Fusarium Free, Masked, and Emerging Mycotoxin Metabolites in Maize from Agriculture Regions of South Africa

by Theodora Ijeoma Ekwomadu, Toluwase Adeseye Dada, Nancy Nleya, Ramokone Gopane, Michael Sulyok and Mulunda Mwanza

Toxins 2020, 12(3), 149; https://doi.org/10.3390/toxins12030149 - 28 Feb 2020

Cited by 42 | Viewed by 4477

Abstract

The presence of mycotoxins in cereal grain is a very important food safety issue with the occurrence of masked mycotoxins extensively investigated in recent years. This study investigated the variation of different Fusarium metabolites (including the related regulated, masked, and emerging mycotoxin) in [...] Read more.

The presence of mycotoxins in cereal grain is a very important food safety issue with the occurrence of masked mycotoxins extensively investigated in recent years. This study investigated the variation of different Fusarium metabolites (including the related regulated, masked, and emerging mycotoxin) in maize from various agriculture regions of South Africa. The relationship between the maize producing regions, the maize type, as well as the mycotoxins was established. A total of 123 maize samples was analyzed by a LC-MS/MS multi-mycotoxin method. The results revealed that all maize types exhibited a mixture of free, masked, and emerging mycotoxins contamination across the regions with an average of 5 and up to 24 out of 42 investigated Fusarium mycotoxins, including 1 to 3 masked forms at the same time. Data obtained show that fumonisin B_1, B_2, B_3, B₄, and A₁ were the most prevalent mycotoxins and had maximum contamination levels of 8908, 3383, 990, 1014, and 51.5 µg/kg, respectively. Deoxynivalenol occurred in 50% of the samples with a mean concentration of 152 µg/kg (max 1380 µg/kg). Thirty-three percent of the samples were contaminated with zearalenone at a mean concentration of 13.6 µg/kg (max 146 µg/kg). Of the masked mycotoxins, DON-3-glucoside occurred at a high incidence level of 53%. Among emerging toxins, moniliformin, fusarinolic acid, and beauvericin showed high occurrences at 98%, 98%, and 83%, and had maximum contamination levels of 1130, 3422, and 142 µg/kg, respectively. Significant differences in the contamination pattern were observed between the agricultural regions and maize types. Full article

(This article belongs to the Special Issue Application of LC-MS/MS in the Mycotoxins Studies)

28 pages, 2725 KiB

Open AccessEditor’s ChoiceReview

Aflatoxin Biosynthesis and Genetic Regulation: A Review

by Isaura Caceres, Anthony Al Khoury, Rhoda El Khoury, Sophie Lorber, Isabelle P. Oswald, André El Khoury, Ali Atoui, Olivier Puel and Jean-Denis Bailly

Toxins 2020, 12(3), 150; https://doi.org/10.3390/toxins12030150 - 28 Feb 2020

Cited by 226 | Viewed by 14913

Abstract

The study of fungal species evolved radically with the development of molecular techniques and produced new evidence to understand specific fungal mechanisms such as the production of toxic secondary metabolites. Taking advantage of these technologies to improve food safety, the molecular study of [...] Read more.

The study of fungal species evolved radically with the development of molecular techniques and produced new evidence to understand specific fungal mechanisms such as the production of toxic secondary metabolites. Taking advantage of these technologies to improve food safety, the molecular study of toxinogenic species can help elucidate the mechanisms underlying toxin production and enable the development of new effective strategies to control fungal toxicity. Numerous studies have been made on genes involved in aflatoxin B1 (AFB1) production, one of the most hazardous carcinogenic toxins for humans and animals. The current review presents the roles of these different genes and their possible impact on AFB1 production. We focus on the toxinogenic strains Aspergillus flavus and A. parasiticus, primary contaminants and major producers of AFB1 in crops. However, genetic reports on A. nidulans are also included because of the capacity of this fungus to produce sterigmatocystin, the penultimate stable metabolite during AFB1 production. The aim of this review is to provide a general overview of the AFB1 enzymatic biosynthesis pathway and its link with the genes belonging to the AFB1 cluster. It also aims to illustrate the role of global environmental factors on aflatoxin production and the recent data that demonstrate an interconnection between genes regulated by these environmental signals and aflatoxin biosynthetic pathway. Full article

(This article belongs to the Special Issue Production Mechanisms and Biosynthesis of Aflatoxin)

► Show Figures

Figure 1

44 pages, 2888 KiB

Open AccessEditor’s ChoiceReview

Human Biomonitoring of Mycotoxins in Blood, Plasma and Serum in Recent Years: A Review

by Beatriz Arce-López, Elena Lizarraga, Ariane Vettorazzi and Elena González-Peñas

Toxins 2020, 12(3), 147; https://doi.org/10.3390/toxins12030147 - 27 Feb 2020

Cited by 86 | Viewed by 9865

Abstract

This manuscript reviews the state-of-the-art regarding human biological monitoring (HBM) of mycotoxins in plasma, serum and blood samples. After a comprehensive and systematic literature review, with a focus on the last five years, several aspects were analyzed and summarized: (a) the biomarkers analyzed [...] Read more.

This manuscript reviews the state-of-the-art regarding human biological monitoring (HBM) of mycotoxins in plasma, serum and blood samples. After a comprehensive and systematic literature review, with a focus on the last five years, several aspects were analyzed and summarized: (a) the biomarkers analyzed and their encountered levels, (b) the analytical methodologies developed and (c) the relationship between biomarker levels and some illnesses. In the literature reviewed, aflatoxin B1-lysine (AFB1-lys) and ochratoxin A (OTA) in plasma and serum were the most widely studied mycotoxin biomarkers for HBM. Regarding analytical methodologies, a clear increase in the development of methods for the simultaneous determination of multiple mycotoxins has been observed. For this purpose, the use of liquid chromatography (LC) methodologies, especially when coupled with tandem mass spectrometry (MS/MS) or high resolution mass spectrometry (HRMS) has grown. A high percentage of the samples analyzed for OTA or aflatoxin B1 (mostly as AFB1-lys) in the reviewed papers were positive, demonstrating human exposure to mycotoxins. This review confirms the importance of mycotoxin human biomonitoring and highlights the important challenges that should be faced, such as the inclusion of other mycotoxins in HBM programs, the need to increase knowledge of mycotoxin metabolism and toxicokinetics, and the need for reference materials and new methodologies for treating samples. In addition, guidelines are required for analytical method validation, as well as equations to establish the relationship between human fluid levels and mycotoxin intake. Full article

(This article belongs to the Section Mycotoxins)

► Show Figures

Figure 1

13 pages, 2345 KiB

Open AccessEditor’s ChoiceArticle

Assessment of the Effect of Satureja montana and Origanum virens Essential Oils on Aspergillus flavus Growth and Aflatoxin Production at Different Water Activities

by Marta García-Díaz, Jessica Gil-Serna, Belén Patiño, Esther García-Cela, Naresh Magan and Ángel Medina

Toxins 2020, 12(3), 142; https://doi.org/10.3390/toxins12030142 - 25 Feb 2020

Cited by 21 | Viewed by 5041

Abstract

Aflatoxin contamination of foodstuffs poses a serious risk to food security, and it is essential to search for new control methods to prevent these toxins entering the food chain. Several essential oils are able to reduce the growth and mycotoxin biosynthesis of toxigenic [...] Read more.

Aflatoxin contamination of foodstuffs poses a serious risk to food security, and it is essential to search for new control methods to prevent these toxins entering the food chain. Several essential oils are able to reduce the growth and mycotoxin biosynthesis of toxigenic species, although their efficiency is strongly influenced by the environmental conditions. In this work, the effectiveness of Satureja montana and Origanum virens essential oils to control Aspergillus flavus growth was evaluated under three water activity levels (0.94, 0.96 and 0.98 a_w) using a Bioscreen C, a rapid in vitro spectrophotometric technique. The aflatoxin concentrations at all conditions tested were determined by HPLC-FLD. Aspergillus flavus growth was delayed by both essential oil treatments. However, only S. montana essential oil was able to significantly affect aflatoxin production, although the inhibition percentages widely differed among water activities. The most significant reduction was observed at 0.96 a_w, which is coincident with the conditions in which A. flavus reached the highest levels of aflatoxin production. On the contrary, the treatment with S. montana essential oil was not effective in significantly reducing aflatoxin production at 0.94 a_w. Therefore, it is important to study the interaction of the new control compounds with environmental factors before their application in food matrices, and in vitro ecophysiological studies are a good option since they provide accurate and rapid results. Full article

(This article belongs to the Special Issue Aflatoxins: Food Sources, Occurrence and Toxicological Effects)

► Show Figures

Graphical abstract

10 pages, 2100 KiB

Open AccessEditor’s ChoiceArticle

Effect of Ozone and Electron Beam Irradiation on Degradation of Zearalenone and Ochratoxin A

by Kai Yang, Ke Li, Lihong Pan, Xiaohu Luo, Jiali Xing, Jing Wang, Li Wang, Ren Wang, Yuheng Zhai and Zhengxing Chen

Toxins 2020, 12(2), 138; https://doi.org/10.3390/toxins12020138 - 24 Feb 2020

Cited by 54 | Viewed by 4064

Abstract

Zearalenone (ZEN) and ochratoxin A (OTA) are key concerns of the food industry because of their toxicity and pollution scope. This study investigated the effects of ozone and electron beam irradiation (EBI) on the degradation of ZEN and OTA. Results demonstrated that 2 [...] Read more.

Zearalenone (ZEN) and ochratoxin A (OTA) are key concerns of the food industry because of their toxicity and pollution scope. This study investigated the effects of ozone and electron beam irradiation (EBI) on the degradation of ZEN and OTA. Results demonstrated that 2 mL of 50 μg/mL ZEN was completely degraded after 10 s of treatment by 2.0 mg/L ozone. The degradation rate of 1 μg/mL ZEN by 16 kGy EBI was 92.76%. Methanol was superior to acetonitrile in terms of degrading ZEN when the irradiation dose was higher than 6 kGy. The degradation rate of 2 mL of 5 μg/mL OTA by 50 mg/L ozone at 180 s was 34%, and that of 1 μg/mL OTA by 16 kGy EBI exceeded 90%. Moreover, OTA degraded more rapidly in acetonitrile. Ozone performed better in the degradation of ZEN, whereas EBI was better for OTA. The conclusions provide theoretical and practical bases for the degradation of different fungal toxins. Full article

(This article belongs to the Special Issue Mycotoxins Study: Toxicology, Identification and Control)

► Show Figures

Figure 1

12 pages, 2528 KiB

Open AccessEditor’s ChoiceArticle

A Lateral Flow Strip Based on a Truncated Aptamer-Complementary Strand for Detection of Type-B Aflatoxins in Nuts and Dried Figs

by Zhilei Zhao, He Wang, Wenlei Zhai, Xiaoyuan Feng, Xia Fan, Ailiang Chen and Meng Wang

Toxins 2020, 12(2), 136; https://doi.org/10.3390/toxins12020136 - 22 Feb 2020

Cited by 51 | Viewed by 5082

Abstract

Type-B aflatoxins (AFB₁ and AFB₂) frequently contaminate food, especially nuts and fried figs, and seriously threaten human health; hence, it is necessary for the newly rapid and sensitive detection methods to prevent the consumption of potentially contaminated food. Here, a [...] Read more.

Type-B aflatoxins (AFB₁ and AFB₂) frequently contaminate food, especially nuts and fried figs, and seriously threaten human health; hence, it is necessary for the newly rapid and sensitive detection methods to prevent the consumption of potentially contaminated food. Here, a lateral flow aptasensor for the detection of type-B aflatoxins was developed. It is based on the use of fluorescent dye Cy5 as a label for the aptamer, and on the competition between type-B aflatoxins and the complementary DNA of the aptamer. This is the first time that the complementary strand of the aptamer has been used as the test line (T-line) to detect type-B aflatoxins. In addition, the truncated aptamer was used to improve the affinity with type-B aflatoxins in our study. Therefore, the lengths of aptamer and cDNA probe were optimized as key parameters for higher sensitivity. In addition, binding buffer and organic solvent were investigated. The results showed that the best pair for achieving improved sensitivity and accuracy in detecting AFB₁ was formed by a shorter aptamer (32 bases) coupled with the probe complementary to the AFB₁ binding region of the aptamer. Under the optimal experimental conditions, the test strip showed an excellent linear relationship in the range from 0.2 to 20 ng/mL with a limit of detection of 0.16 ng/mL. This aptamer-based strip was successfully applied to the determination of type-B aflatoxins in spiked and commercial peanuts, almonds, and dried figs, and the recoveries of the spiked samples were from 93.3%−112.0%. The aptamer-complementary strand-based lateral flow test strip is a potential alternative tool for the rapid and sensitive detection of type-B aflatoxins in nuts and dried figs. It is of help for monitoring aflatoxins to avoid the consumption of unsafe food. Full article

(This article belongs to the Section Mycotoxins)

► Show Figures

Figure 1

15 pages, 2344 KiB

Open AccessEditor’s ChoiceArticle

Toxicity Characterisation of Gambierdiscus Species from the Canary Islands

by Araceli E. Rossignoli, Angels Tudó, Isabel Bravo, Patricio A. Díaz, Jorge Diogène and Pilar Riobó

Toxins 2020, 12(2), 134; https://doi.org/10.3390/toxins12020134 - 21 Feb 2020

Cited by 35 | Viewed by 5318

Abstract

In the last decade, several outbreaks of ciguatera fish poisoning (CFP) have been reported in the Canary Islands (central northeast Atlantic Ocean), confirming ciguatera as an emerging alimentary risk in this region. Five Gambierdiscus species, G. australes, G. excentricus, G. silvae [...] Read more.

In the last decade, several outbreaks of ciguatera fish poisoning (CFP) have been reported in the Canary Islands (central northeast Atlantic Ocean), confirming ciguatera as an emerging alimentary risk in this region. Five Gambierdiscus species, G. australes, G. excentricus, G. silvae, G. carolinianus and G. caribaeus, have been detected in macrophytes from this area and are known to produce the ciguatoxins (CTXs) that cause CFP. A characterization of the toxicity of these species is the first step in identifying locations in the Canary Islands at risk of CFP. Therefore, in this study the toxicity of 63 strains of these five Gambierdiscus species were analysed using the erythrocyte lysis assay to evaluate their maitotoxin (MTX) content. In addition, 20 of the strains were also analysed in a neuroblastoma Neuro-2a (N2a) cytotoxicity assay to determine their CTX-like toxicity. The results allowed the different species to be grouped according to their ratios of CTX-like and MTX-like toxicity. MTX-like toxicity was especially high in G. excentricus and G. australes but much lower in the other species and lowest in G. silvae. CTX-like toxicity was highest in G. excentricus, which produced the toxin in amounts ranging between 128.2 ± 25.68 and 510.6 ± 134.2 fg CTX1B equivalents (eq) cell⁻¹ (mean ± SD). In the other species, CTX concentrations were as follows: G. carolinianus (100.84 ± 18.05 fg CTX1B eq cell⁻¹), G. australes (31.1 ± 0.56 to 107.16 ± 21.88 fg CTX1B eq cell⁻¹), G. silvae (12.19 ± 0.62 to 76.79 ± 4.97 fg CTX1B eq cell⁻¹) and G. caribaeus (<LOD to 90.37 ± 15.89 fg CTX1B eq cell⁻¹). Unlike the similar CTX-like toxicity of G. australes and G. silvae strains from different locations, G. excentricus and G. caribaeus differed considerably according to the origin of the strain. These differences emphasise the importance of species identification to assess the regional risk of CFP. Full article

(This article belongs to the Special Issue Potentially Toxic Benthic Microorganisms in Freshwater and Marine Ecosystems)

► Show Figures

Figure 1

12 pages, 942 KiB

Open AccessEditor’s ChoiceArticle

Varespladib (LY315920) and Methyl Varespladib (LY333013) Abrogate or Delay Lethality Induced by Presynaptically Acting Neurotoxic Snake Venoms

by José María Gutiérrez, Matthew R. Lewin, David. J. Williams and Bruno Lomonte

Toxins 2020, 12(2), 131; https://doi.org/10.3390/toxins12020131 - 20 Feb 2020

Cited by 68 | Viewed by 7490

Abstract

The phospholipase A₂ (PLA₂) inhibitor Varespladib (LY315920) and its orally bioavailable prodrug, methyl-Varespladib (LY333013) inhibit PLA₂ activity of a wide variety of snake venoms. In this study, the ability of these two forms of Varespladib to halt or delay [...] Read more.

The phospholipase A₂ (PLA₂) inhibitor Varespladib (LY315920) and its orally bioavailable prodrug, methyl-Varespladib (LY333013) inhibit PLA₂ activity of a wide variety of snake venoms. In this study, the ability of these two forms of Varespladib to halt or delay lethality of potent neurotoxic snake venoms was tested in a mouse model. The venoms of Notechis scutatus, Crotalus durissus terrificus, Bungarus multicinctus, and Oxyuranus scutellatus, all of which have potent presynaptically acting neurotoxic PLA₂s of variable quaternary structure, were used to evaluate simple dosing regimens. A supralethal dose of each venom was injected subcutaneously in mice, followed by the bolus intravenous (LY315920) or oral (LY333013) administration of the inhibitors, immediately and at various time intervals after envenoming. Control mice receiving venom alone died within 3 h of envenoming. Mice injected with O. scutellatus venom and treated with LY315920 or LY333013 survived the 24 h observation period, whereas those receiving C. d. terrificus and B. multicinctus venoms survived at 3 h or 6 h with a single dose of either form of Varespladib, but not at 24 h. In contrast, mice receiving N. scutatus venom and then the inhibitors died within 3 h, similarly to the control animals injected with venom alone. LY315920 was able to reverse the severe paralytic manifestations in mice injected with venoms of O. scutellatus, B. multicinctus, and C. d. terrificus. Overall, results suggest that the two forms of Varespladib are effective in abrogating, or delaying, neurotoxic manifestations induced by some venoms whose neurotoxicity is mainly dependent on presynaptically acting PLA₂s. LY315920 is able to reverse paralytic manifestations in severely envenomed mice, but further work is needed to understand the significance of species-specific differences in animal models as they compare to clinical syndromes in human and for potential use in veterinary medicine. Full article

(This article belongs to the Section Animal Venoms)

► Show Figures

Graphical abstract

13 pages, 2502 KiB

Open AccessEditor’s ChoiceArticle

Phytotoxic Metabolites Isolated from Neufusicoccum batangarum, the Causal Agent of the Scabby Canker of Cactus Pear (Opuntia ficus-indica L.)

by Marco Masi, Francesco Aloi, Paola Nocera, Santa Olga Cacciola, Giuseppe Surico and Antonio Evidente

Toxins 2020, 12(2), 126; https://doi.org/10.3390/toxins12020126 - 18 Feb 2020

Cited by 25 | Viewed by 4280

Abstract

Six phytotoxins were obtained from the culture filtrates of the ascomycete Neofusicoccum batangarum, the causal agent of the scabby canker of cactus pear (Opuntia ficus-indica L.) in minor Sicily islands. The phytotoxins were identified as (−)-(R)-mellein (1); [...] Read more.

Six phytotoxins were obtained from the culture filtrates of the ascomycete Neofusicoccum batangarum, the causal agent of the scabby canker of cactus pear (Opuntia ficus-indica L.) in minor Sicily islands. The phytotoxins were identified as (−)-(R)-mellein (1); (±)-botryoisocoumarin A (2); (−)-(3R,4R)- and (−)-(3R,4S)-4-hydroxymellein (3 and 4); (−)-terpestacin (5); and (+)-3,4-dihydro-4,5,8-trihydroxy-3-methylisocoumarin, which we named (+)-neoisocoumarin (6). This identification was done by comparing their spectral and optical data with those already reported in literature. The absolute configuration (3R,4S) to (+)-neoisocoumarin (6) was determined using the advanced Mosher method. All six metabolites were shown to have phytotoxicity on the host (cactus pear) and non-host (tomato) plants, and the most active compounds were (±)-botryoisocoumarin A (2), (−)-terpestacin (5), and (+)-neoisocoumarin (6). Full article

(This article belongs to the Special Issue Microbial and Plant Phytotoxins)

► Show Figures

Graphical abstract

11 pages, 295 KiB

Open AccessEditor’s ChoiceReview

Mechanism of Action of Botulinum Toxin A in Treatment of Functional Urological Disorders

by Yu-Hua Lin, Bing-Juin Chiang and Chun-Hou Liao

Toxins 2020, 12(2), 129; https://doi.org/10.3390/toxins12020129 - 18 Feb 2020

Cited by 33 | Viewed by 4329

Abstract

Intravesical botulinum toxin (BoNT) injection is effective in reducing urgency and urinary incontinence. It temporarily inhibits the detrusor muscle contraction by blocking the release of acetylcholine (Ach) from the preganglionic and postganglionic nerves in the efferent nerves. BoNT-A also blocks ATP release from [...] Read more.

Intravesical botulinum toxin (BoNT) injection is effective in reducing urgency and urinary incontinence. It temporarily inhibits the detrusor muscle contraction by blocking the release of acetylcholine (Ach) from the preganglionic and postganglionic nerves in the efferent nerves. BoNT-A also blocks ATP release from purinergic efferent nerves in the detrusor muscle. In afferent nerves, BoNT-A injection markedly reduces the urothelial ATP release and increases nitric oxide (NO) release from the urothelium. BoNT-A injection in the urethra or bladder has been developed in the past few decades as the treatment method for detrusor sphincter dyssyndergia, incontinence due to neurogenic or idiopathic detrusor overactivity, sensory disorders, including bladder hypersensitivity, overactive bladder, and interstitial cystitis/chronic pelvic pain syndrome. Although the FDA only approved BoNT-A injection treatment for neurogenic detrusor overactivity and for refractory overactive bladder, emerging clinical trials have demonstrated the benefits of BoNT-A treatment in functional urological disorders. Cautious selection of patients and urodynamic evaluation for confirmation of diagnosis are crucial to maximize the successful outcomes of BoNT-A treatment. Full article

(This article belongs to the Special Issue Botulinum Toxin Treatment for Pain and Inflammation in Functional Urological Disorders)

17 pages, 2678 KiB

Open AccessEditor’s ChoiceReview

Comparing the Efficacy of OnabotulinumtoxinA, Sacral Neuromodulation, and Peripheral Tibial Nerve Stimulation as Third Line Treatment for the Management of Overactive Bladder Symptoms in Adults: Systematic Review and Network Meta-Analysis

by Chi-Wen Lo, Mei-Yi Wu, Stephen Shei-Dei Yang, Fu-Shan Jaw and Shang-Jen Chang

Toxins 2020, 12(2), 128; https://doi.org/10.3390/toxins12020128 - 18 Feb 2020

Cited by 38 | Viewed by 6332

Abstract

The American Urological Association guidelines for the management of non-neurogenic overactive bladder (OAB) recommend the use of OnabotulinumtoxinA, sacral neuromodulation (SNM), and peripheral tibial nerve stimulation (PTNS) as third line treatment options with no treatment hierarchy. The current study used network meta-analysis to [...] Read more.

The American Urological Association guidelines for the management of non-neurogenic overactive bladder (OAB) recommend the use of OnabotulinumtoxinA, sacral neuromodulation (SNM), and peripheral tibial nerve stimulation (PTNS) as third line treatment options with no treatment hierarchy. The current study used network meta-analysis to compare the efficacy of these three modalities for managing adult OAB syndrome. We performed systematic literature searches of several databases from January 1995 to September 2019 with language restricted to English. All randomized control trials that compared any dose of OnabotulinumtoxinA, SNM, and PTNS with each other or a placebo for the management of adult OAB were included in the study. Overall, 17 randomized control trials, with a follow up of 3–6 months in the predominance of trials (range 1.5–24 months), were included for analysis. For each trial outcome, the results were reported as an average number of episodes of the outcome at baseline. Compared with the placebo, all three treatments were more efficacious for the selected outcome parameters. OnabotulinumtoxinA resulted in a higher number of complications, including urinary tract infection and urine retention. Compared with OnabotulinumtoxinA and PTNS, SNM resulted in the greatest reduction in urinary incontinence episodes and voiding frequency. However, comparison of their long-term efficacy was lacking. Further studies on the long-term effectiveness of the three treatment options, with standardized questionnaires and parameters are warranted. Full article

(This article belongs to the Special Issue Botulinum Toxin Treatment for Pain and Inflammation in Functional Urological Disorders)

► Show Figures

Figure 1

10 pages, 2260 KiB

Open AccessEditor’s ChoiceArticle

Rapid, Sensitive, and Accurate Point-of-Care Detection of Lethal Amatoxins in Urine

by Candace S. Bever, Kenneth D. Swanson, Elizabeth I. Hamelin, Michael Filigenzi, Robert H. Poppenga, Jennifer Kaae, Luisa W. Cheng and Larry H. Stanker

Toxins 2020, 12(2), 123; https://doi.org/10.3390/toxins12020123 - 15 Feb 2020

Cited by 25 | Viewed by 11834

Abstract

Globally, mushroom poisonings cause about 100 human deaths each year, with thousands of people requiring medical assistance. Dogs are also susceptible to mushroom poisonings and require medical assistance. Cyclopeptides, and more specifically amanitins (or amatoxins, here), are the mushroom poison that causes the [...] Read more.

Globally, mushroom poisonings cause about 100 human deaths each year, with thousands of people requiring medical assistance. Dogs are also susceptible to mushroom poisonings and require medical assistance. Cyclopeptides, and more specifically amanitins (or amatoxins, here), are the mushroom poison that causes the majority of these deaths. Current methods (predominantly chromatographic, as well as antibody-based) of detecting amatoxins are time-consuming and require expensive equipment. In this work, we demonstrate the utility of the lateral flow immunoassay (LFIA) for the rapid detection of amatoxins in urine samples. The LFIA detects as little as 10 ng/mL of α-amanitin (α-AMA) or γ-AMA, and 100 ng/mL of β-AMA in urine matrices. To demonstrate application of this LFIA for urine analysis, this study examined fortified human urine samples and urine collected from exposed dogs. Urine is sampled directly without the need for any pretreatment, detection from urine is completed in 10 min, and the results are read by eye, without the need for specialized equipment. Analysis of both fortified human urine samples and urine samples collected from intoxicated dogs using the LFIA correlated well with liquid chromatography–mass spectrometry (LC-MS) methods. Full article

(This article belongs to the Special Issue Improved Analytical Technologies for the Detection of Natural Toxins and Their Metabolites in Food)

► Show Figures

Graphical abstract

21 pages, 2018 KiB

Open AccessEditor’s ChoiceReview

Methicillin-Resistant Staphylococcus aureus ST80 Clone: A Systematic Review

by Assia Mairi, Abdelaziz Touati and Jean-Philippe Lavigne

Toxins 2020, 12(2), 119; https://doi.org/10.3390/toxins12020119 - 14 Feb 2020

Cited by 34 | Viewed by 5669

Abstract

This review assessed the molecular characterization of the methicillin-resistant Staphylococcus aureus (MRSA)-ST80 clone with an emphasis on its proportion of total MRSA strains isolated, PVL production, spa-typing, antibiotic resistance, and virulence. A systematic review of the literature was conducted on MRSA-ST80 clone [...] Read more.

This review assessed the molecular characterization of the methicillin-resistant Staphylococcus aureus (MRSA)-ST80 clone with an emphasis on its proportion of total MRSA strains isolated, PVL production, spa-typing, antibiotic resistance, and virulence. A systematic review of the literature was conducted on MRSA-ST80 clone published between 1 January 2000 and 31 August 2019. Citations were chosen for a review of the full text if we found evidence that MRSA-ST80 clone was reported in the study. For each isolate, the country of isolation, the sampling period, the source of isolation (the type of infection, nasal swabs, or extra-human), the total number of MRSA strains isolated, number of MRSA-ST80 strains, antibiotic resistance patterns, PVL production, virulence genes, and spa type were recorded. The data from 103 articles were abstracted into an Excel database. Analysis of the data showed that the overall proportion of MRSA-ST80 has been decreasing in many countries in recent years. The majority of MRSA-ST80 were PVL positive with spa-type t044. Only six reports of MRSA-ST80 in extra-human niches were found. This review summarizes the rise of MRSA-ST80 and the evidence that suggests that it could be in decline in many countries. Full article

(This article belongs to the Special Issue Methicillin-Resistant Staphylococci and Macrococci at the Interface of Human and Animal Health)

► Show Figures

Figure 1

37 pages, 3901 KiB

Open AccessEditor’s ChoiceReview

Detoxification of Mycotoxins through Biotransformation

by Peng Li, Ruixue Su, Ruya Yin, Daowan Lai, Mingan Wang, Yang Liu and Ligang Zhou

Toxins 2020, 12(2), 121; https://doi.org/10.3390/toxins12020121 - 14 Feb 2020

Cited by 109 | Viewed by 10841

Abstract

Mycotoxins are toxic fungal secondary metabolites that pose a major threat to the safety of food and feed. Mycotoxins are usually converted into less toxic or non-toxic metabolites through biotransformation that are often made by living organisms as well as the isolated enzymes. [...] Read more.

Mycotoxins are toxic fungal secondary metabolites that pose a major threat to the safety of food and feed. Mycotoxins are usually converted into less toxic or non-toxic metabolites through biotransformation that are often made by living organisms as well as the isolated enzymes. The conversions mainly include hydroxylation, oxidation, hydrogenation, de-epoxidation, methylation, glycosylation and glucuronidation, esterification, hydrolysis, sulfation, demethylation and deamination. Biotransformations of some notorious mycotoxins such as alfatoxins, alternariol, citrinin, fomannoxin, ochratoxins, patulin, trichothecenes and zearalenone analogues are reviewed in detail. The recent development and applications of mycotoxins detoxification through biotransformation are also discussed. Full article

(This article belongs to the Section Mycotoxins)

► Show Figures

Figure 1

15 pages, 4498 KiB

Open AccessEditor’s ChoiceArticle

Mitochondria and Lysosomes Participate in Vip3Aa-Induced Spodoptera frugiperda Sf9 Cell Apoptosis

by Xiaoyue Hou, Lu Han, Baoju An, Yanli Zhang, Zhanglei Cao, Yunda Zhan, Xia Cai, Bing Yan and Jun Cai

Toxins 2020, 12(2), 116; https://doi.org/10.3390/toxins12020116 - 13 Feb 2020

Cited by 34 | Viewed by 3811

Abstract

Vip3Aa, a soluble protein produced by certain Bacillus thuringiensis strains, is capable of inducing apoptosis in Sf9 cells. However, the apoptosis mechanism triggered by Vip3Aa is unclear. In this study, we found that Vip3Aa induces mitochondrial dysfunction, as evidenced by signs of collapse [...] Read more.

Vip3Aa, a soluble protein produced by certain Bacillus thuringiensis strains, is capable of inducing apoptosis in Sf9 cells. However, the apoptosis mechanism triggered by Vip3Aa is unclear. In this study, we found that Vip3Aa induces mitochondrial dysfunction, as evidenced by signs of collapse of mitochondrial membrane potential, accumulation of reactive oxygen species, release of cytochrome c, and caspase-9 and -3 activation. Meanwhile, our results indicated that Vip3Aa reduces the ability of lysosomes in Sf9 cells to retain acridine orange. Moreover, pretreatment with Z-Phe-Tyr-CHO (a cathepsin L inhibitor) or pepstatin (a cathepsin D inhibitor) increased Sf9 cell viability, reduced cytochrome c release, and decreased caspase-9 and -3 activity. In conclusion, our findings suggested that Vip3Aa promotes Sf9 cell apoptosis by mitochondrial dysfunction, and lysosomes also play a vital role in the action of Vip3Aa. Full article

(This article belongs to the Special Issue Bacillus thuringiensis Toxins: Functional Characterization and Mechanism of Action)

► Show Figures

Figure 1

14 pages, 1851 KiB

Open AccessEditor’s ChoiceArticle

Zearalenone Removal from Corn Oil by an Enzymatic Strategy

by Xiaojiao Chang, Hujun Liu, Jing Sun, Jun Wang, Chengcheng Zhao, Wan Zhang, Jie Zhang and Changpo Sun

Toxins 2020, 12(2), 117; https://doi.org/10.3390/toxins12020117 - 13 Feb 2020

Cited by 53 | Viewed by 4652

Abstract

The estrogen-like mycotoxin zearalenone (ZEN) is one of the most widely distributed contaminants especially in maize and its commodities, such as corn oil. ZEN degrading enzymes possess the potential for counteracting the negative effect of ZEN and its associated high safety risk in [...] Read more.

The estrogen-like mycotoxin zearalenone (ZEN) is one of the most widely distributed contaminants especially in maize and its commodities, such as corn oil. ZEN degrading enzymes possess the potential for counteracting the negative effect of ZEN and its associated high safety risk in corn oil. Herein, we targeted enhancing the secretion of ZEN degrading enzyme by Pichia pastoris through constructing an expression plasmid containing three optimized expression cassettes of zlhy-6 codon and signal peptides. Further, we explored various parameters of enzymatic detoxification in neutralized oil and analyzed tocopherols and sterols losses in the corn oil. In addition, the distribution of degraded products was demonstrated as well by Agilent 6510 Quadrupole Time-of-Flight mass spectrometry. P. pastoris GSZ with the glucoamylase signal was observed with the highest ZLHY-6 secretion yield of 0.39 mg/mL. During the refining of corn oil, ZEN in the crude oil was reduced from 1257.3 to 13 µg/kg (3.69% residual) after neutralization and enzymatic detoxification. Compared with the neutralized oil, no significant difference in the total tocopherols and sterols contents was detected after enzymatic detoxification. Finally, the degraded products were found to be entirely eliminated by washing. This study presents an enzymatic strategy for efficient and safe ZEN removal with relatively low nutrient loss, which provides an important basis for further application of enzymatic ZEN elimination in the industrial process of corn oil production. Full article

► Show Figures

Graphical abstract

16 pages, 1569 KiB

Open AccessEditor’s ChoiceArticle

Ultra-High-Performance Liquid Chromatography Coupled with Quadrupole Orbitrap High-Resolution Mass Spectrometry for Multi-Residue Analysis of Mycotoxins and Pesticides in Botanical Nutraceuticals

by Alfonso Narváez, Yelko Rodríguez-Carrasco, Luigi Castaldo, Luana Izzo and Alberto Ritieni

Toxins 2020, 12(2), 114; https://doi.org/10.3390/toxins12020114 - 12 Feb 2020

Cited by 48 | Viewed by 7174

Abstract

Cannabidiol (CBD) food supplements made of Cannabis sativa L. extracts have quickly become popular products due to their health-promoting effects. However, potential contaminants, such as mycotoxins and pesticides, can be coextracted during the manufacturing process and placed into the final product. Accordingly, a [...] Read more.

Cannabidiol (CBD) food supplements made of Cannabis sativa L. extracts have quickly become popular products due to their health-promoting effects. However, potential contaminants, such as mycotoxins and pesticides, can be coextracted during the manufacturing process and placed into the final product. Accordingly, a novel methodology using ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was developed to quantify 16 mycotoxins produced by major C. sativa fungi, followed by a post-target screening of 283 pesticides based on a comprehensive spectral library. The validated procedure was applied to ten CBD-based products. Up to six different Fusarium mycotoxins were found in seven samples, the most prevalent being zearalenone (60%) and enniatin B1 (30%), both found at a maximum level of 11.6 ng/g. Co-occurrence was observed in four samples, including one with enniatin B1, enniatin A and enniatin A1. On the other hand, 46 different pesticides were detected after retrospective analysis. Ethoxyquin (50%), piperonyl butoxide (40%), simazine (30%) and cyanazine (30%) were the major residues found. These results highlight the necessity of monitoring contaminants in food supplements in order to ensure a safe consumption, even more considering the increase trend in their use. Furthermore, the developed procedure is proposed as a powerful analytical tool to evaluate the potential mycotoxin profile of these particular products. Full article

(This article belongs to the Special Issue Application of LC-MS/MS in the Mycotoxins Studies)

► Show Figures

Figure 1

17 pages, 1823 KiB

Open AccessEditor’s ChoiceArticle

The Effectiveness of Durian Peel as a Multi-Mycotoxin Adsorbent

by Saowalak Adunphatcharaphon, Awanwee Petchkongkaew, Donato Greco, Vito D’Ascanio, Wonnop Visessanguan and Giuseppina Avantaggiato

Toxins 2020, 12(2), 108; https://doi.org/10.3390/toxins12020108 - 8 Feb 2020

Cited by 44 | Viewed by 7828

Abstract

Durian peel (DP) is an agricultural waste that is widely used in dyes and for organic and inorganic pollutant adsorption. In this study, durian peel was acid-treated to enhance its mycotoxin adsorption efficacy. The acid-treated durian peel (ATDP) was assessed for simultaneous adsorption [...] Read more.

Durian peel (DP) is an agricultural waste that is widely used in dyes and for organic and inorganic pollutant adsorption. In this study, durian peel was acid-treated to enhance its mycotoxin adsorption efficacy. The acid-treated durian peel (ATDP) was assessed for simultaneous adsorption of aflatoxin B₁ (AFB₁), ochratoxin A (OTA), zearalenone (ZEA), deoxynivalenol (DON), and fumonisin B₁ (FB₁). The structure of the ATDP was also characterized by SEM–EDS, FT–IR, a zetasizer, and a surface-area analyzer. The results indicated that ATDP exhibited the highest mycotoxin adsorption towards AFB₁ (98.4%), ZEA (98.4%), and OTA (97.3%), followed by FB₁ (86.1%) and DON (2.0%). The pH significantly affected OTA and FB₁ adsorption, whereas AFB₁ and ZEA adsorption was not affected. Toxin adsorption by ATDP was dose-dependent and increased exponentially as the ATDP dosage increased. The maximum adsorption capacity (Q_max), determined at pH 3 and pH 7, was 40.7 and 41.6 mmol kg⁻¹ for AFB₁, 15.4 and 17.3 mmol kg⁻¹ for ZEA, 46.6 and 0.6 mmol kg⁻¹ for OTA, and 28.9 and 0.1 mmol kg⁻¹ for FB₁, respectively. Interestingly, ATDP reduced the bioaccessibility of these mycotoxins after gastrointestinal digestion using an in vitro, validated, static model. The ATDP showed a more porous structure, with a larger surface area and a surface charge modification. These structural changes following acid treatment may explain the higher efficacy of ATDP in adsorbing mycotoxins. Hence, ATDP can be considered as a promising waste material for mycotoxin biosorption. Full article

(This article belongs to the Special Issue Mycotoxin Contamination Management Tools and Efficient Strategies in Feed Industry)

► Show Figures

Graphical abstract

12 pages, 2568 KiB

Open AccessEditor’s ChoiceArticle

Chronic Microcystin-LR Exposure Induces Abnormal Lipid Metabolism via Endoplasmic Reticulum Stress in Male Zebrafish

by Dandan Zhang, Wang Lin, Yinjie Liu, Honghui Guo, Lingkai Wang, Liping Yang, Li Li, Dapeng Li and Rong Tang

Toxins 2020, 12(2), 107; https://doi.org/10.3390/toxins12020107 - 7 Feb 2020

Cited by 38 | Viewed by 4795

Abstract

In order to explore effects of low levels of continuous microcystin-LR (MC-LR) (a cyanotoxin) exposure on hepatic lipid metabolism on the basis of the endoplasmic reticulum stress (ERS) pathway, we exposed adult male zebrafish to MC-LR (0, 1, 5, and 25 μg/L) for [...] Read more.

In order to explore effects of low levels of continuous microcystin-LR (MC-LR) (a cyanotoxin) exposure on hepatic lipid metabolism on the basis of the endoplasmic reticulum stress (ERS) pathway, we exposed adult male zebrafish to MC-LR (0, 1, 5, and 25 μg/L) for 60 days, and hepatic histopathology as well as lipid metabolic parameters were determined with mRNA levels of ERS signal molecules and downstream factors, along with genes associated with lipid metabolism in zebrafish liver. The results revealed that prolonged exposure to MC-LR remarkably altered the levels of hepatic total cholesterol and triglyceride and led to hepatic steatosis, which was also confirmed by hepatic cytoplasmic vacuolization in Hematoxylin/eosin (H&E) stain and lipid droplet accumulation in Oil Red O stain. The severity of hepatic damage and lipidation was increased in a dose-related manner. MC-LR exposure significantly upregulated transcriptional levels of ERS markers including hspa5, mapk8, and chop, indicating the occurrence of ERS in the liver of zebrafish. Concurrently, MC-LR significantly improved mRNA expression of unfolded protein response (UPR) pathway-related genes including atf6, eif2ak3, ern1, and xbp1s, suggesting that all of the three UPR branches were activated by MC-LR. MC-LR also induced significant upregulation of downstream lipid metabolism-related factors and genes including srebf1, srebf2, fatty acid synthase (fasn), acetyl-CoA carboxylase (acaca), stearoyl-CoA desaturase (scd), HMG CoA reductase (hmgcra), and HMG CoA synthase (hmgcs1), and downregulation of genes associated with lipolysis such as triglyceride hydrolase gene (atgl), hormone-sensitive enzyme gene (hsla), and carnitine palmitoyltransferase gene (cpt1aa). Our present results indicated that the cause of hepatic lipid accumulation by MC-LR was mainly by upregulating lipogenic and cholesterol genes but downregulating the expression of lipolytic genes through the induction of srebf1 and srebf2, which were involved in the activation of ERS signal pathways. Full article

(This article belongs to the Special Issue Advances in the Toxicity Mechanisms of Microcystins Revealed by Omics Approaches)

► Show Figures

Figure 1

23 pages, 1861 KiB

Open AccessEditor’s ChoiceArticle

In Vitro Rumen Simulations Show a Reduced Disappearance of Deoxynivalenol, Nivalenol and Enniatin B at Conditions of Rumen Acidosis and Lower Microbial Activity

by Sandra Debevere, An Cools, Siegrid De Baere, Geert Haesaert, Michael Rychlik, Siska Croubels and Veerle Fievez

Toxins 2020, 12(2), 101; https://doi.org/10.3390/toxins12020101 - 5 Feb 2020

Cited by 42 | Viewed by 4507

Abstract

Ruminants are generally considered to be less susceptible to the effects of mycotoxins than monogastric animals as the rumen microbiota are capable of detoxifying some of these toxins. Despite this potential degradation, mycotoxin-associated subclinical health problems are seen in dairy cows. In this [...] Read more.

Ruminants are generally considered to be less susceptible to the effects of mycotoxins than monogastric animals as the rumen microbiota are capable of detoxifying some of these toxins. Despite this potential degradation, mycotoxin-associated subclinical health problems are seen in dairy cows. In this research, the disappearance of several mycotoxins was determined in an in vitro rumen model and the effect of realistic concentrations of those mycotoxins on fermentation was assessed by volatile fatty acid production. In addition, two hypotheses were tested: (1) a lower rumen pH leads to a decreased degradation of mycotoxins and (2) rumen fluid of lactating cows degrade mycotoxins better than rumen fluid of non-lactating cows. Maize silage was spiked with a mixture of deoxynivalenol (DON), nivalenol (NIV), enniatin B (ENN B), mycophenolic acid (MPA), roquefortine C (ROQ-C) and zearalenone (ZEN). Fresh rumen fluid of two lactating cows (L) and two non-lactating cows (N) was added to a buffer of normal pH (6.8) and low pH (5.8), leading to four combinations (L6.8, L5.8, N6.8, N5.8), which were added to the spiked maize substrate. In this study, mycotoxins had no effect on volatile fatty acid production. However, not all mycotoxins fully disappeared during incubation. ENN B and ROQ-C disappeared only partially, whereas MPA showed almost no disappearance. The disappearance of DON, NIV, and ENN B was hampered when pH was low, especially when the inoculum of non-lactating cows was used. For ZEN, a limited transformation of ZEN to α-ZEL and β-ZEL was observed, but only at pH 6.8. In conclusion, based on the type of mycotoxin and the ruminal conditions, mycotoxins can stay intact in the rumen. Full article

(This article belongs to the Special Issue Mycotoxins in Feed: Harm to Animals)

► Show Figures

Figure 1

8 pages, 299 KiB

Open AccessEditor’s ChoiceArticle

Aflatoxin M₁ Determination in Infant Formulae Distributed in Monterrey, Mexico

by Patricia A. Quevedo-Garza, Genaro G. Amador-Espejo, Rogelio Salas-García, Esteban G. Ramos-Peña and Antonio-José Trujillo

Toxins 2020, 12(2), 100; https://doi.org/10.3390/toxins12020100 - 4 Feb 2020

Cited by 29 | Viewed by 3458

Abstract

The occurrence of aflatoxin M₁ (AFM₁) in infant formulae commercialized in the metropolitan area of Monterrey (Nuevo León, Mexico) was determined by using immunoaffinity column clean-up followed by HPLC determination with fluorimetric detection. For this, 55 infant formula powders were [...] Read more.

The occurrence of aflatoxin M₁ (AFM₁) in infant formulae commercialized in the metropolitan area of Monterrey (Nuevo León, Mexico) was determined by using immunoaffinity column clean-up followed by HPLC determination with fluorimetric detection. For this, 55 infant formula powders were classified in two groups, starter (49 samples) and follow-on (6 samples) formulae. Eleven of the evaluated samples (20%) presented values above the permissible limit set by the European Union for infant formulae (25 ng/L), ranging from 40 to 450 ng/L. The estimated daily intake (EDI) for AFM₁ was determined employing the average body weight (bw) of the groups of age in the ranges of 0–6 and 6–12 months, and 1–2 years. The results evidenced high intake values, ranging from 1.56 to 14 ng/kg bw/day, depending on the group. Finally, with the EDI value, the carcinogenic risk index was determined, presenting a high risk for all the evaluated groups. Based on these results, it is a necessary extra effort by the regulatory agencies to reduce the AFM₁ presence in infant formulae consumed in Mexico. Full article

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

15 pages, 3046 KiB

Open AccessEditor’s ChoiceArticle

Domain Shuffling between Vip3Aa and Vip3Ca: Chimera Stability and Insecticidal Activity against European, American, African, and Asian Pests

by Joaquín Gomis-Cebolla, Rafael Ferreira dos Santos, Yueqin Wang, Javier Caballero, Primitivo Caballero, Kanglai He, Juan Luis Jurat-Fuentes and Juan Ferré

Toxins 2020, 12(2), 99; https://doi.org/10.3390/toxins12020099 - 4 Feb 2020

Cited by 16 | Viewed by 3982

Abstract

The bacterium Bacillus thuringiensis produces insecticidal Vip3 proteins during the vegetative growth phase with activity against several lepidopteran pests. To date, three different Vip3 protein families have been identified based on sequence identity: Vip3A, Vip3B, and Vip3C. In this study, we report the [...] Read more.

The bacterium Bacillus thuringiensis produces insecticidal Vip3 proteins during the vegetative growth phase with activity against several lepidopteran pests. To date, three different Vip3 protein families have been identified based on sequence identity: Vip3A, Vip3B, and Vip3C. In this study, we report the construction of chimeras by exchanging domains between Vip3Aa and Vip3Ca, two proteins with marked specificity differences against lepidopteran pests. We found that some domain combinations made proteins insoluble or prone to degradation by trypsin as most abundant insect gut protease. The soluble and trypsin-stable chimeras, along with the parental proteins Vip3Aa and Vip3Ca, were tested against lepidopteran pests from different continents: Spodoptera exigua, Spodoptera littoralis, Spodoptera frugiperda, Helicoverpa armigera, Mamestra brassicae, Anticarsia gemmatalis, and Ostrinia furnacalis. The exchange of the Nt domain (188 N-terminal amino acids) had little effect on the stability and toxicity (equal or slightly lower) of the resulting chimeric protein against all insects except for S. frugiperda, for which the chimera with the Nt domain from Vip3Aa and the rest of the protein from Vip3Ca showed a significant increase in toxicity compared to the parental Vip3Ca. Chimeras with the C-terminal domain from Vip3Aa (from amino acid 510 of Vip3Aa to the Ct) with the central domain of Vip3Ca (amino acids 189–509 based on the Vip3Aa sequence) made proteins that could not be solubilized. Finally, the chimera including the Ct domain of Vip3Ca and the Nt and central domain from Vip3Aa was unstable. Importantly, an insect species tolerant to Vip3Aa but susceptible to Vip3Ca, such as Ostrinia furnacalis, was also susceptible to chimeras maintaining the Ct domain from Vip3Ca, in agreement with the hypothesis that the Ct region of the protein is the one conferring specificity to Vip3 proteins. Full article

(This article belongs to the Special Issue Bacillus thuringiensis Toxins: Functional Characterization and Mechanism of Action)

► Show Figures

Graphical abstract

32 pages, 2688 KiB

Open AccessEditor’s ChoiceArticle

Cultivation Area Affects the Presence of Fungal Communities and Secondary Metabolites in Italian Durum Wheat Grains

by Giovanni Beccari, Antonio Prodi, Maria Teresa Senatore, Virgilio Balmas, Francesco Tini, Andrea Onofri, Luca Pedini, Michael Sulyok, Luca Brocca and Lorenzo Covarelli

Toxins 2020, 12(2), 97; https://doi.org/10.3390/toxins12020097 - 3 Feb 2020

Cited by 26 | Viewed by 5165

Abstract

In this study, durum wheat kernels harvested in three climatically different Italian cultivation areas (Emilia Romagna, Umbria and Sardinia) in 2015, were analyzed with a combination of different isolation methods to determine their fungal communities, with a focus on Fusarium head blight (FHB) [...] Read more.

In this study, durum wheat kernels harvested in three climatically different Italian cultivation areas (Emilia Romagna, Umbria and Sardinia) in 2015, were analyzed with a combination of different isolation methods to determine their fungal communities, with a focus on Fusarium head blight (FHB) complex composition, and to detect fungal secondary metabolites in the grains. The genus Alternaria was the main component of durum wheat mycobiota in all investigated regions, with the Central Italian cultivation area showing the highest incidence of this fungal genus and of its secondary metabolites. Fusarium was the second most prevalent genus of the fungal community in all cultivation environments, even if regional differences in species composition were detected. In particular, Northern areas showed the highest Fusarium incidence, followed by Central and then Southern cultivation areas. Focusing on the FHB complex, a predominance of Fusarium poae, in particular in Northern and Central cultivation areas, was found. Fusarium graminearum, in the analyzed year, was mainly detected in Emilia Romagna. Because of the highest Fusarium incidence, durum wheat harvested in the Northern cultivation area showed the highest presence of Fusarium secondary metabolites. These results show that durum wheat cultivated in Northern Italy may be subject to a higher FHB infection risk and to Fusarium mycotoxins accumulation. Full article

(This article belongs to the Section Mycotoxins)

► Show Figures

Graphical abstract

19 pages, 2918 KiB

Open AccessEditor’s ChoiceArticle

Inflammatory Reaction Induced by Two Metalloproteinases Isolated from Bothrops atrox Venom and by Fragments Generated from the Hydrolysis of Basement Membrane Components

by Michelle Teixeira de Almeida, Luciana Aparecida Freitas-de-Sousa, Monica Colombini, Sarah N. C. Gimenes, Eduardo S. Kitano, Eliana L. Faquim-Mauro, Solange M. T. Serrano and Ana Maria Moura-da-Silva

Toxins 2020, 12(2), 96; https://doi.org/10.3390/toxins12020096 - 2 Feb 2020

Cited by 29 | Viewed by 3606

Abstract

Snake venom metalloproteinases (SVMPs) play an important role in local tissue damage of snakebite patients, mostly by hydrolysis of basement membrane (BM) components. We evaluated the proinflammatory activity of SVMPs Atroxlysin-Ia (ATXL) and Batroxrhagin (BATXH) from Bothrops atrox venom and their hydrolysis products [...] Read more.

Snake venom metalloproteinases (SVMPs) play an important role in local tissue damage of snakebite patients, mostly by hydrolysis of basement membrane (BM) components. We evaluated the proinflammatory activity of SVMPs Atroxlysin-Ia (ATXL) and Batroxrhagin (BATXH) from Bothrops atrox venom and their hydrolysis products of Matrigel. BALB/c mice were injected with SVMPs (2 μg), for assessment of paw edema and peritoneal leukocyte accumulation. Both SVMPs induced edema, representing an increase of ~70% of the paw size. Leukocyte infiltrates reached levels of 6 × 10⁶ with ATXL and 5 × 10⁶ with BATXH. TNF-α was identified in the supernatant of BATXH—or venom-stimulated MPAC cells. Incubation of Matrigel with the SVMPs generated fragments, including peptides from Laminin, identified by LC–MS/MS. The Matrigel hydrolysis peptides caused edema that increased 30% the paw size and promoted leukocyte accumulation (4–5 × 10⁶) to the peritoneal cavity, significantly higher than Matrigel control peptides 1 and 4 h after injection. Our findings suggest that ATXL and BATXH are involved in the inflammatory reaction observed in B. atrox envenomings by direct action on inflammatory cells or by releasing proinflammatory peptides from BM proteins that may amplify the direct action of SVMPs through activation of endogenous signaling pathways. Full article

(This article belongs to the Section Animal Venoms)

► Show Figures

Figure 1

11 pages, 1898 KiB

Open AccessEditor’s ChoiceArticle

A Liquid Chromatographic Method for Rapid and Sensitive Analysis of Aflatoxins in Laboratory Fungal Cultures

by Ahmad F. Alshannaq and Jae-Hyuk Yu

Toxins 2020, 12(2), 93; https://doi.org/10.3390/toxins12020093 - 30 Jan 2020

Cited by 19 | Viewed by 6017

Abstract

Culture methods supplemented with high-performance liquid chromatography (HPLC) technique provide a rapid and simple tool for detecting levels of aflatoxins (AFs) produced by fungi. This study presents a robust method for simultaneous quantification of aflatoxin (AF) B1, B2, G1, and G2 levels in [...] Read more.

Culture methods supplemented with high-performance liquid chromatography (HPLC) technique provide a rapid and simple tool for detecting levels of aflatoxins (AFs) produced by fungi. This study presents a robust method for simultaneous quantification of aflatoxin (AF) B1, B2, G1, and G2 levels in several fungal cultivation states: submerged shake culture, liquid slant culture, and solid-state culture. The recovery of the method was evaluated by spiking a mixture of AFs at several concentrations to the test medium. The applicability of the method was evaluated by using aflatoxigenic and non-aflatoxigenic Aspergilli. A HPLC coupled with the diode array (DAD) and fluorescence (FLD) detectors was used to determine the presence and amounts of AFs. Both detectors showed high sensitivity in detecting spiked AFs or AFs produced in situ by toxigenic fungi. Our methods showed 76%–88% recovery from medium spiked with 2.5, 10, 50, 100, and 500 ng/mL AFs. The limit of quantification (LOQ) for AFs were 2.5 to 5.0 ng/mL with DAD and 0.025 to 2.5 ng/mL with FLD. In this work, we described in detail a protocol, which can be considered the foremost and only verified method, to extract, detect, and quantify AFs employing both aflatoxigenic and non-toxigenic Aspergilli. Full article

(This article belongs to the Special Issue Rapid Detection of Mycotoxin Contamination)

► Show Figures

Figure 1

13 pages, 2854 KiB

Open AccessEditor’s ChoiceArticle

T-2 Toxin Induces Oxidative Stress, Apoptosis and Cytoprotective Autophagy in Chicken Hepatocytes

by Huadong Yin, Shunshun Han, Yuqi Chen, Yan Wang, Diyan Li and Qing Zhu

Toxins 2020, 12(2), 90; https://doi.org/10.3390/toxins12020090 - 29 Jan 2020

Cited by 54 | Viewed by 4554

Abstract

T-2 toxin is type A trichothecenes mycotoxin, which produced by fusarium species in cereal grains. T-2 toxin has been shown to induce a series of toxic effects on the health of human and animal, such as immunosuppression and carcinogenesis. Previous study has proven [...] Read more.

T-2 toxin is type A trichothecenes mycotoxin, which produced by fusarium species in cereal grains. T-2 toxin has been shown to induce a series of toxic effects on the health of human and animal, such as immunosuppression and carcinogenesis. Previous study has proven that T-2 toxin caused hepatotoxicity in chicken, but the regulatory mechanism is unclear. In the present study, we assessed the toxicological effect of T-2 toxin on apoptosis and autophagy in hepatocytes. The total of 120 1-day-old healthy broilers were allocated randomly into four groups and reared for 21 day with complete feed containing 0 mg/kg, 0.5 mg/kg, 1 mg/kg or 2 mg/kg T-2 toxin, respectively. The results showed that the apoptosis rate and pathological changes degree hepatocytes were aggravated with the increase of T-2 toxin. At the molecular mechanism level, T-2 toxin induced mitochondria-mediated apoptosis by producing reactive oxygen species, promoting cytochrome c translocation between the mitochondria and cytoplasm, and thus promoting apoptosomes formation. Meanwhile, the expression of the autophagy-related protein, ATG5, ATG7 and Beclin-1, and the LC3-II/LC3-I ratio were increased, while p62 was downregulated, suggesting T-2 toxin caused autophagy in hepatocytes. Further experiments demonstrated that the PI3K/AKT/mTOR signal may be participated in autophagy induced by T-2 toxin in chicken hepatocytes. These data suggest a possible underlying molecular mechanism for T-2 toxin that induces apoptosis and autophagy in chicken hepatocytes Full article

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

► Show Figures

Figure 1

10 pages, 884 KiB

Open AccessEditor’s ChoiceArticle

Acute Oral Toxicity of Pinnatoxin G in Mice

by Silvio Sosa, Marco Pelin, Federica Cavion, Fabienne Hervé, Philipp Hess and Aurelia Tubaro

Toxins 2020, 12(2), 87; https://doi.org/10.3390/toxins12020087 - 28 Jan 2020

Cited by 30 | Viewed by 4461

Abstract

Pinnatoxin G (PnTx-G) is a marine cyclic imine toxin produced by the dinoflagellate Vulcanodinium rugosum, frequently detected in edible shellfish from Ingril Lagoon (France). As other pinnatoxins, to date, no human poisonings ascribed to consumption of PnTx-G contaminated seafood have been reported, [...] Read more.

Pinnatoxin G (PnTx-G) is a marine cyclic imine toxin produced by the dinoflagellate Vulcanodinium rugosum, frequently detected in edible shellfish from Ingril Lagoon (France). As other pinnatoxins, to date, no human poisonings ascribed to consumption of PnTx-G contaminated seafood have been reported, despite its potent antagonism at nicotinic acetylcholine receptors and its high and fast-acting toxicity after intraperitoneal or oral administration in mice. The hazard characterization of PnTx-G by oral exposure is limited to a single acute toxicity study recording lethality and clinical signs in non-fasted mice treated by gavage or through voluntary food ingestion, which showed differences in PnTx-G toxic potency. Thus, an acute toxicity study was carried out using 3 h-fasted CD-1 female mice, administered by gavage with PnTx-G (8–450 µg kg⁻¹). At the dose of 220 µg kg⁻¹ and above, the toxin induced a rapid onset of clinical signs (piloerection, prostration, hypothermia, abdominal breathing, paralysis of the hind limbs, and cyanosis), leading to the death of mice within 30 min. Except for moderate mucosal degeneration in the small intestine recorded at doses of 300 µg kg⁻¹, the toxin did not induce significant morphological changes in the other main organs and tissues, or alterations in blood chemistry parameters. This acute oral toxicity study allowed to calculate an oral LD₅₀ for PnTx-G equal to 208 μg kg⁻¹ (95% confidence limits: 155–281 µg kg⁻¹) and to estimate a provisional NOEL of 120 µg kg⁻¹. Full article

(This article belongs to the Special Issue Potentially Toxic Benthic Microorganisms in Freshwater and Marine Ecosystems)

► Show Figures

Figure 1

22 pages, 1204 KiB

Open AccessEditor’s ChoiceArticle

Molecular Epidemiology of Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus in Wild, Captive and Laboratory Rats: Effect of Habitat on the Nasal S. aureus Population

by Dina Raafat, Daniel M. Mrochen, Fawaz Al’Sholui, Elisa Heuser, René Ryll, Kathleen R. Pritchett-Corning, Jens Jacob, Bernd Walther, Franz-Rainer Matuschka, Dania Richter, Uta Westerhüs, Jiri Pikula, Jens van den Brandt, Werner Nicklas, Stefan Monecke, Birgit Strommenger, Sarah van Alen, Karsten Becker, Rainer G. Ulrich and Silva Holtfreter

Toxins 2020, 12(2), 80; https://doi.org/10.3390/toxins12020080 - 24 Jan 2020

Cited by 22 | Viewed by 6087

Abstract

Rats are a reservoir of human- and livestock-associated methicillin-resistant Staphylococcus aureus (MRSA). However, the composition of the natural S. aureus population in wild and laboratory rats is largely unknown. Here, 144 nasal S. aureus isolates from free-living wild rats, captive wild rats and [...] Read more.

Rats are a reservoir of human- and livestock-associated methicillin-resistant Staphylococcus aureus (MRSA). However, the composition of the natural S. aureus population in wild and laboratory rats is largely unknown. Here, 144 nasal S. aureus isolates from free-living wild rats, captive wild rats and laboratory rats were genotyped and profiled for antibiotic resistances and human-specific virulence genes. The nasal S. aureus carriage rate was higher among wild rats (23.4%) than laboratory rats (12.3%). Free-living wild rats were primarily colonized with isolates of clonal complex (CC) 49 and CC130 and maintained these strains even in husbandry. Moreover, upon livestock contact, CC398 isolates were acquired. In contrast, laboratory rats were colonized with many different S. aureus lineages—many of which are commonly found in humans. Five captive wild rats were colonized with CC398-MRSA. Moreover, a single CC30-MRSA and two CC130-MRSA were detected in free-living or captive wild rats. Rat-derived S. aureus isolates rarely harbored the phage-carried immune evasion gene cluster or superantigen genes, suggesting long-term adaptation to their host. Taken together, our study revealed a natural S. aureus population in wild rats, as well as a colonization pressure on wild and laboratory rats by exposure to livestock- and human-associated S. aureus, respectively. Full article

(This article belongs to the Special Issue Methicillin-Resistant Staphylococci and Macrococci at the Interface of Human and Animal Health)

► Show Figures

Figure 1

15 pages, 6311 KiB

Open AccessEditor’s ChoiceArticle

Bioprospecting Sponge-Associated Marine Cyanobacteria to Produce Bioactive Compounds

by Despoina Konstantinou, Eleni Mavrogonatou, Sevasti-Kiriaki Zervou, Panagiotis Giannogonas and Spyros Gkelis

Toxins 2020, 12(2), 73; https://doi.org/10.3390/toxins12020073 - 23 Jan 2020

Cited by 23 | Viewed by 7490

Abstract

Marine cyanobacteria are considered a prolific source of bioactive natural products with a range of biotechnological and pharmacological applications. However, data on the production of natural compounds from sponge-associated cyanobacteria are scarce. This study aimed to assess the potential of sponge-associated cyanobacteria strains [...] Read more.

Marine cyanobacteria are considered a prolific source of bioactive natural products with a range of biotechnological and pharmacological applications. However, data on the production of natural compounds from sponge-associated cyanobacteria are scarce. This study aimed to assess the potential of sponge-associated cyanobacteria strains representing different taxonomic groups for the production of bioactive compounds and the biological activity of their extracts. Phylogenetic analysis of sponge-associated cyanobacteria and screening for the presence of genes encoding non-ribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) were performed. Methanol extracts of the sponge-associated strains were analyzed for cyanotoxin production and tested for antioxidant activity and cytotoxic activity against several human cancer cell lines and pathogenic bacteria. PKS were detected in all sponge-associated strains examined, indicating the metabolic potential of the isolates. PKS genes were more ubiquitous than NRPS genes. Cyanotoxins (i.e., cylindrospermopsin, anatoxin-a, nodularin, and microcystins) were not detected in any of the sponge-associated cyanobacterial strains. Strains belonging to Leptothoe, Pseudanabaena, and Synechococcus were found to have activity mainly against Staphylococcus aureus. In addition, sponge-associated Leptothoe strains (TAU-MAC 0915, 1015, 1115, and 1215) were found to be highly cytotoxic and in most cases more effective against human cancer cell lines than against normal cells. Extracts with the most promising bioactivity deserve further investigation in order to isolate and identify the bioactive molecule(s). Full article

(This article belongs to the Special Issue Selected Papers from the 11th International Conference on Toxic Cyanobacteria)

► Show Figures

Figure 1

12 pages, 1331 KiB

Open AccessEditor’s ChoiceArticle

Diet Breadth Mediates the Prey Specificity of Venom Potency in Snakes

by Keith Lyons, Michel M. Dugon and Kevin Healy

Toxins 2020, 12(2), 74; https://doi.org/10.3390/toxins12020074 - 23 Jan 2020

Cited by 46 | Viewed by 7776

Abstract

Venoms are best known for their ability to incapacitate prey. In predatory groups, venom potency is predicted to reflect ecological and evolutionary drivers relating to diet. While venoms have been found to have prey-specific potencies, the role of diet breadth on venom potencies [...] Read more.

Venoms are best known for their ability to incapacitate prey. In predatory groups, venom potency is predicted to reflect ecological and evolutionary drivers relating to diet. While venoms have been found to have prey-specific potencies, the role of diet breadth on venom potencies has yet to be tested at large macroecological scales. Here, using a comparative analysis of 100 snake species, we show that the evolution of prey-specific venom potencies is contingent on the breadth of a species’ diet. We find that while snake venom is more potent when tested on species closely related to natural prey items, we only find this prey-specific pattern in species with taxonomically narrow diets. While we find that the taxonomic diversity of a snakes’ diet mediates the prey specificity of its venom, the species richness of its diet was not found to affect these prey-specific potency patterns. This indicates that the physiological diversity of a species’ diet is an important driver of the evolution of generalist venom potencies. These findings suggest that the venoms of species with taxonomically diverse diets may be better suited to incapacitating novel prey species and hence play an important role for species within changing environments. Full article

(This article belongs to the Special Issue Evolutionary Ecology of Venom)

► Show Figures

Figure 1

15 pages, 1359 KiB

Open AccessEditor’s ChoiceArticle

Isolation and Characterization of [D-Leu¹]microcystin-LY from Microcystis aeruginosa CPCC-464

by Patricia LeBlanc, Nadine Merkley, Krista Thomas, Nancy I. Lewis, Khalida Békri, Susan LeBlanc Renaud, Frances R. Pick, Pearse McCarron, Christopher O. Miles and Michael A. Quilliam

Toxins 2020, 12(2), 77; https://doi.org/10.3390/toxins12020077 - 23 Jan 2020

Cited by 16 | Viewed by 3964

Abstract

[D-Leu¹]MC-LY (1) ([M + H]⁺ m/z 1044.5673, Δ 2.0 ppm), a new microcystin, was isolated from Microcystis aeruginosa strain CPCC-464. The compound was characterized by ¹H and ¹³C NMR spectroscopy, liquid chromatography–high resolution tandem [...] Read more.

[D-Leu¹]MC-LY (1) ([M + H]⁺ m/z 1044.5673, Δ 2.0 ppm), a new microcystin, was isolated from Microcystis aeruginosa strain CPCC-464. The compound was characterized by ¹H and ¹³C NMR spectroscopy, liquid chromatography–high resolution tandem mass spectrometry (LC–HRMS/MS) and UV spectroscopy. A calibration reference material was produced after quantitation by ¹H NMR spectroscopy and LC with chemiluminescence nitrogen detection. The potency of 1 in a protein phosphatase 2A inhibition assay was essentially the same as for MC-LR (2). Related microcystins, [D-Leu¹]MC-LR (3) ([M + H]⁺ m/z 1037.6041, Δ 1.0 ppm), [D-Leu¹]MC-M(O)R (6) ([M + H]⁺ m/z 1071.5565, Δ 2.0 ppm) and [D-Leu¹]MC-MR (7) ([M + H]⁺ m/z 1055.5617, Δ 2.2 ppm), were also identified in culture extracts, along with traces of [D-Leu¹]MC-M(O₂)R (8) ([M + H]⁺ m/z 1087.5510, Δ 1.6 ppm), by a combination of chemical derivatization and LC–HRMS/MS experiments. The relative abundances of 1, 3, 6, 7 and 8 in a freshly extracted culture in the positive ionization mode LC–HRMS were ca. 84, 100, 3.0, 11 and 0.05, respectively. These and other results indicate that [D-Leu¹]-containing MCs may be more common in cyanobacterial blooms than is generally appreciated but are easily overlooked with standard targeted LC–MS/MS screening methods. Full article

(This article belongs to the Special Issue Freshwater Algal Toxins: Monitoring and Toxicity Profile)

► Show Figures

Figure 1

26 pages, 1819 KiB

Open AccessEditor’s ChoiceReview

Amplification of Snake Venom Toxicity by Endogenous Signaling Pathways

by Philip E. Bickler

Toxins 2020, 12(2), 68; https://doi.org/10.3390/toxins12020068 - 22 Jan 2020

Cited by 60 | Viewed by 17305

Abstract

The active components of snake venoms encompass a complex and variable mixture of proteins that produce a diverse, but largely stereotypical, range of pharmacologic effects and toxicities. Venom protein diversity and host susceptibilities determine the relative contributions of five main pathologies: neuromuscular dysfunction, [...] Read more.

The active components of snake venoms encompass a complex and variable mixture of proteins that produce a diverse, but largely stereotypical, range of pharmacologic effects and toxicities. Venom protein diversity and host susceptibilities determine the relative contributions of five main pathologies: neuromuscular dysfunction, inflammation, coagulopathy, cell/organ injury, and disruption of homeostatic mechanisms of normal physiology. In this review, we describe how snakebite is not only a condition mediated directly by venom, but by the amplification of signals dysregulating inflammation, coagulation, neurotransmission, and cell survival. Although venom proteins are diverse, the majority of important pathologic events following envenoming follow from a small group of enzyme-like activities and the actions of small toxic peptides. This review focuses on two of the most important enzymatic activities: snake venom phospholipases (svPLA₂) and snake venom metalloproteases (svMP). These two enzyme classes are adept at enabling venom to recruit homologous endogenous signaling systems with sufficient magnitude and duration to produce and amplify cell injury beyond what would be expected from the direct impact of a whole venom dose. This magnification produces many of the most acutely important consequences of envenoming as well as chronic sequelae. Snake venom PLA₂s and MPs enzymes recruit prey analogs of similar activity. The transduction mechanisms that recruit endogenous responses include arachidonic acid, intracellular calcium, cytokines, bioactive peptides, and possibly dimerization of venom and prey protein homologs. Despite years of investigation, the precise mechanism of svPLA₂-induced neuromuscular paralysis remains incomplete. Based on recent studies, paralysis results from a self-amplifying cycle of endogenous PLA₂ activation, arachidonic acid, increases in intracellular Ca²⁺ and nicotinic receptor deactivation. When prolonged, synaptic suppression supports the degeneration of the synapse. Interaction between endothelium-damaging MPs, sPLA₂s and hyaluronidases enhance venom spread, accentuating venom-induced neurotoxicity, inflammation, coagulopathy and tissue injury. Improving snakebite treatment requires new tools to understand direct and indirect effects of envenoming. Homologous PLA₂ and MP activities in both venoms and prey/snakebite victim provide molecular targets for non-antibody, small molecule agents for dissecting mechanisms of venom toxicity. Importantly, these tools enable the separation of venom-specific and prey-specific pathological responses to venom. Full article

(This article belongs to the Special Issue Novel Strategies for the Diagnosis and Treatment of Snakebites)

► Show Figures

Figure 1

22 pages, 6180 KiB

Open AccessEditor’s ChoiceArticle

Ostreopsis cf. ovata (Dinophyceae) Molecular Phylogeny, Morphology, and Detection of Ovatoxins in Strains and Field Samples from Brazil

by Silvia M. Nascimento, Raquel A. F. Neves, Gabriela A. L. De’Carli, Geovanna T. Borsato, Rodrigo A. F. da Silva, Guilherme A. Melo, Agatha M. de Morais, Thais C. Cockell, Santiago Fraga, Adriana D. Menezes-Salgueiro, Luiz L. Mafra, Philipp Hess and Fabiano Salgueiro

Toxins 2020, 12(2), 70; https://doi.org/10.3390/toxins12020070 - 22 Jan 2020

Cited by 20 | Viewed by 4050

Abstract

Recurrent blooms of Ostreopsis cf. ovata have been reported in Brazil and the Mediterranean Sea with associated ecological, and in the latter case, health impacts. Molecular data based on the D1–D3 and D8–D10 regions of the LSU rDNA and ITS loci, and the [...] Read more.

Recurrent blooms of Ostreopsis cf. ovata have been reported in Brazil and the Mediterranean Sea with associated ecological, and in the latter case, health impacts. Molecular data based on the D1–D3 and D8–D10 regions of the LSU rDNA and ITS loci, and the morphology of O. cf. ovata isolates and field populations from locations along the Brazilian tropical and subtropical coastal regions and three oceanic islands are presented. Additional ITS sequences from three single cells from the tropical coast are provided. Toxin profiles and quantities of PLTX and their analogues; OVTXs; contained in cells from two clonal cultures and two field blooms from Rio de Janeiro were investigated. Morphology was examined using both light and epifluorescence microscopy. Morphometric analysis of different strains and field populations from diverse locations were compared. Molecular analysis showed that six of the seven sequences grouped at the large “Atlantic/Mediterranean/Pacific” sub-clade, while one sequence branched in a sister clade with sequences from Madeira Island and Greece. The toxin profile of strains and bloom field samples from Rio de Janeiro were dominated by OVTX-a and -b, with total cell quotas (31.3 and 39.3 pg cell⁻¹) in the range of that previously reported for strains of O. cf. ovata. Full article

(This article belongs to the Special Issue Potentially Toxic Benthic Microorganisms in Freshwater and Marine Ecosystems)

► Show Figures

Figure 1

22 pages, 3218 KiB

Open AccessEditor’s ChoiceReview

Bacterial Genotoxin-Induced DNA Damage and Modulation of the Host Immune Microenvironment

by Océane C.B. Martin and Teresa Frisan

Toxins 2020, 12(2), 63; https://doi.org/10.3390/toxins12020063 - 21 Jan 2020

Cited by 45 | Viewed by 5995

Abstract

Bacterial genotoxins (BTGX) induce DNA damage, which results in senescence or apoptosis of the target cells if not properly repaired. Three BTGXs have been identified: the cytolethal distending toxin (CDT) family produced by several Gram-negative bacteria, the typhoid toxin produced by several Salmonella [...] Read more.

Bacterial genotoxins (BTGX) induce DNA damage, which results in senescence or apoptosis of the target cells if not properly repaired. Three BTGXs have been identified: the cytolethal distending toxin (CDT) family produced by several Gram-negative bacteria, the typhoid toxin produced by several Salmonella enterica serovars, and colibactin, a peptide-polyketide, produced mainly by the phylogenetic group B2 Escherichia coli. The cellular responses induced by BTGXs resemble those of well-characterized carcinogenic agents, and several lines of evidence indicate that bacteria carrying genotoxin genes can contribute to tumor development under specific circumstances. Given their unusual mode of action, it is still enigmatic why these effectors have been acquired by microbes and what is their role in the context of the biology of the producing bacterium, since it is unlikely that their primary purpose is to induce/promote cancer in the mammalian host. In this review, we will discuss the possibility that the DNA damage induced by BTGX modulates the host immune response, acting as immunomodulator, leading to the establishment of a suitable niche for the producing bacterium. We will further highlight open questions that remain to be solved regarding the biology of this unusual family of bacterial toxins. Full article

(This article belongs to the Special Issue Current Knowledge on Bacterial Genotoxins and Their Effects on Host Cells)

► Show Figures

Figure 1

15 pages, 1366 KiB

Open AccessEditor’s ChoiceReview

Apitoxin and Its Components against Cancer, Neurodegeneration and Rheumatoid Arthritis: Limitations and Possibilities

by Andreas Aufschnaiter, Verena Kohler, Shaden Khalifa, Aida Abd El-Wahed, Ming Du, Hesham El-Seedi and Sabrina Büttner

Toxins 2020, 12(2), 66; https://doi.org/10.3390/toxins12020066 - 21 Jan 2020

Cited by 61 | Viewed by 10778

Abstract

Natural products represent important sources for the discovery and design of novel drugs. Bee venom and its isolated components have been intensively studied with respect to their potential to counteract or ameliorate diverse human diseases. Despite extensive research and significant advances in recent [...] Read more.

Natural products represent important sources for the discovery and design of novel drugs. Bee venom and its isolated components have been intensively studied with respect to their potential to counteract or ameliorate diverse human diseases. Despite extensive research and significant advances in recent years, multifactorial diseases such as cancer, rheumatoid arthritis and neurodegenerative diseases remain major healthcare issues at present. Although pure bee venom, apitoxin, is mostly described to mediate anti-inflammatory, anti-arthritic and neuroprotective effects, its primary component melittin may represent an anticancer therapeutic. In this review, we approach the possibilities and limitations of apitoxin and its components in the treatment of these multifactorial diseases. We further discuss the observed unspecific cytotoxicity of melittin that strongly restricts its therapeutic use and review interesting possibilities of a beneficial use by selectively targeting melittin to cancer cells. Full article

(This article belongs to the Section Animal Venoms)

► Show Figures

Graphical abstract

46 pages, 2076 KiB

Open AccessEditor’s ChoiceReview

Shiga Toxin-Associated Hemolytic Uremic Syndrome: A Narrative Review

by Adrien Joseph, Aurélie Cointe, Patricia Mariani Kurkdjian, Cédric Rafat and Alexandre Hertig

Toxins 2020, 12(2), 67; https://doi.org/10.3390/toxins12020067 - 21 Jan 2020

Cited by 166 | Viewed by 15856

Abstract

The severity of human infection by one of the many Shiga toxin-producing Escherichia coli (STEC) is determined by a number of factors: the bacterial genome, the capacity of human societies to prevent foodborne epidemics, the medical condition of infected patients (in particular their [...] Read more.

The severity of human infection by one of the many Shiga toxin-producing Escherichia coli (STEC) is determined by a number of factors: the bacterial genome, the capacity of human societies to prevent foodborne epidemics, the medical condition of infected patients (in particular their hydration status, often compromised by severe diarrhea), and by our capacity to devise new therapeutic approaches, most specifically to combat the bacterial virulence factors, as opposed to our current strategies that essentially aim to palliate organ deficiencies. The last major outbreak in 2011 in Germany, which killed more than 50 people in Europe, was evidence that an effective treatment was still lacking. Herein, we review the current knowledge of STEC virulence, how societies organize the prevention of human disease, and how physicians treat (and, hopefully, will treat) its potentially fatal complications. In particular, we focus on STEC-induced hemolytic and uremic syndrome (HUS), where the intrusion of toxins inside endothelial cells results in massive cell death, activation of the coagulation within capillaries, and eventually organ failure. Full article

(This article belongs to the Special Issue Molecular Basis and the Pathogenesis of Enterohemorrhagic Escherichia coli Infections)

► Show Figures

Figure 1

12 pages, 913 KiB

Open AccessEditor’s ChoiceReview

Molecular and Cellular Mechanisms that Induce Arterial Calcification by Indoxyl Sulfate and P-Cresyl Sulfate

by Britt Opdebeeck, Patrick C. D’Haese and Anja Verhulst

Toxins 2020, 12(1), 58; https://doi.org/10.3390/toxins12010058 - 19 Jan 2020

Cited by 46 | Viewed by 6309

Abstract

The protein-bound uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), are considered to be harmful vascular toxins. Arterial media calcification, or the deposition of calcium phosphate crystals in the arteries, contributes significantly to cardiovascular complications, including left ventricular hypertrophy, hypertension, and impaired [...] Read more.

The protein-bound uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), are considered to be harmful vascular toxins. Arterial media calcification, or the deposition of calcium phosphate crystals in the arteries, contributes significantly to cardiovascular complications, including left ventricular hypertrophy, hypertension, and impaired coronary perfusion in the elderly and patients with chronic kidney disease (CKD) and diabetes. Recently, we reported that both IS and PCS trigger moderate to severe calcification in the aorta and peripheral vessels of CKD rats. This review describes the molecular and cellular mechanisms by which these uremic toxins induce arterial media calcification. A complex interplay between inflammation, coagulation, and lipid metabolism pathways, influenced by epigenetic factors, is crucial in IS/PCS-induced arterial media calcification. High levels of glucose are linked to these events, suggesting that a good balance between glucose and lipid levels might be important. On the cellular level, effects on endothelial cells, which act as the primary sensors of circulating pathological triggers, might be as important as those on vascular smooth muscle cells. Endothelial dysfunction, provoked by IS and PCS triggered oxidative stress, may be considered a key event in the onset and development of arterial media calcification. In this review a number of important outstanding questions such as the role of miRNA’s, phenotypic switching of both endothelial and vascular smooth muscle cells and new types of programmed cell death in arterial media calcification related to protein-bound uremic toxins are put forward and discussed. Full article

(This article belongs to the Special Issue Comorbidities in Chronic Kidney Disease (CKD))

► Show Figures

Figure 1

10 pages, 817 KiB

Open AccessEditor’s ChoiceArticle

Patulin Mycotoxin in Mango and Orange Fruits, Juices, Pulps, and Jams Marketed in Pakistan

by Shabbir Hussain, Muhammad Rafique Asi, Mazhar Iqbal, Nisha Khalid, Syed Wajih-ul-Hassan and Agustín Ariño

Toxins 2020, 12(1), 52; https://doi.org/10.3390/toxins12010052 - 16 Jan 2020

Cited by 38 | Viewed by 6120

Abstract

The objective of the study was to explore the incidence of patulin (PAT) mycotoxin in mango and orange fruits and derived products marketed in Pakistan. A total of 274 samples, including 70 mango fruits, 63 mango-based products (juices, pulp, and jam), 77 orange [...] Read more.

The objective of the study was to explore the incidence of patulin (PAT) mycotoxin in mango and orange fruits and derived products marketed in Pakistan. A total of 274 samples, including 70 mango fruits, 63 mango-based products (juices, pulp, and jam), 77 orange fruits, and 64 orange-based products, were collected. PAT was determined by reverse-phase high-performance liquid chromatography (HPLC) with UV-Vis detector (276 nm). Linear detector response was observed (R² > 0.99), the limit of detection (LOD) was 5 µg/kg and recovery percentage was 97.4%. The incidence of PAT in mango samples was 61.7%, and the concentration ranged from <LOD to 6415 µg/kg with a mean of 110.9 µg/kg. Our results showed the high susceptibility of mango fruits to patulin, and it was observed that decayed mango fruits were most contaminated with PAT. Among the mango samples, PAT concentration was higher in fruits than in processed products such as mango juice, pulp, and jam. Toxin incidence in orange samples was 52.5% with concentrations from <LOD to 61 µg/kg and a mean of 6.3 µg/kg. As much as 29 samples of mango (21.8%) contained PAT concentration above the regulatory limit (50 µg/kg), whereas there was only one exceeding orange sample (0.7%). Our results show that PAT seems to be a problem in fruits, juices, and derived solid products, especially from mango, and needs surveillance on regular basis. Full article

(This article belongs to the Special Issue Mycotoxins Study: Toxicology, Identification and Control)

► Show Figures

Figure 1

16 pages, 6888 KiB

Open AccessEditor’s ChoiceArticle

Antivenom Neutralization of Coagulopathic Snake Venom Toxins Assessed by Bioactivity Profiling Using Nanofractionation Analytics

by Chunfang Xie, Julien Slagboom, Laura-Oana Albulescu, Ben Bruyneel, Kristina B. M. Still, Freek J. Vonk, Govert W. Somsen, Nicholas R. Casewell and Jeroen Kool

Toxins 2020, 12(1), 53; https://doi.org/10.3390/toxins12010053 - 16 Jan 2020

Cited by 20 | Viewed by 6712

Abstract

Venomous snakebite is one of the world’s most lethal neglected tropical diseases. Animal-derived antivenoms are the only standardized specific therapies currently available for treating snakebite envenoming, but due to venom variation, often this treatment is not effective in counteracting all clinical symptoms caused [...] Read more.

Venomous snakebite is one of the world’s most lethal neglected tropical diseases. Animal-derived antivenoms are the only standardized specific therapies currently available for treating snakebite envenoming, but due to venom variation, often this treatment is not effective in counteracting all clinical symptoms caused by the multitude of injected toxins. In this study, the coagulopathic toxicities of venoms from the medically relevant snake species Bothrops asper, Calloselasma rhodostoma, Deinagkistrodon acutus, Daboia russelii, Echis carinatus and Echis ocellatus were assessed. The venoms were separated by liquid chromatography (LC) followed by nanofractionation and parallel mass spectrometry (MS). A recently developed high-throughput coagulation assay was employed to assess both the pro- and anticoagulant activity of separated venom toxins. The neutralization capacity of antivenoms on separated venom components was assessed and the coagulopathic venom peptides and enzymes that were either neutralized or remained active in the presence of antivenom were identified by correlating bioassay results with the MS data and with off-line generated proteomics data. The results showed that most snake venoms analyzed contained both procoagulants and anticoagulants. Most anticoagulants were identified as phospholipases A₂s (PLA₂s) and most procoagulants correlated with snake venom metalloproteinases (SVMPs) and serine proteases (SVSPs). This information can be used to better understand antivenom neutralization and can aid in the development of next-generation antivenom treatments. Full article

(This article belongs to the Special Issue Medically Relevant Snake Toxins, Current Antivenoms and the Development of Next-Generation Antivenoms)

► Show Figures

Figure 1

21 pages, 1728 KiB

Open AccessEditor’s ChoiceReview

Ciguatera Fish Poisoning: The Risk from an Aotearoa/New Zealand Perspective

by Lesley L. Rhodes, Kirsty F. Smith, J. Sam Murray, Tomohiro Nishimura and Sarah C. Finch

Toxins 2020, 12(1), 50; https://doi.org/10.3390/toxins12010050 - 15 Jan 2020

Cited by 31 | Viewed by 5089

Abstract

Gambierdiscus and Fukuyoa species have been identified in Aotearoa/New Zealand’s coastal waters and G. polynesiensis, a known producer of ciguatoxins, has been isolated from Rangitāhua/Kermadec Islands (a New Zealand territory). The warming of the Tasman Sea and the waters around New Zealand’s [...] Read more.

Gambierdiscus and Fukuyoa species have been identified in Aotearoa/New Zealand’s coastal waters and G. polynesiensis, a known producer of ciguatoxins, has been isolated from Rangitāhua/Kermadec Islands (a New Zealand territory). The warming of the Tasman Sea and the waters around New Zealand’s northern subtropical coastline heighten the risk of Gambierdiscus proliferating in New Zealand. If this occurs, the risk of ciguatera fish poisoning due to consumption of locally caught fish will increase. Research, including the development and testing of sampling methods, molecular assays, and chemical and toxicity tests, will continue. Reliable monitoring strategies are important to manage and mitigate the risk posed by this emerging threat. The research approaches that have been made, many of which will continue, are summarised in this review. Full article

(This article belongs to the Special Issue Dinoflagellate Toxins)

► Show Figures

Figure 1

12 pages, 1198 KiB

Open AccessEditor’s ChoiceArticle

Dispersive Solid-Phase Extraction using Magnetic Carbon Nanotube Composite for the Determination of Emergent Mycotoxins in Urine Samples

by Natalia Arroyo-Manzanares, Rosa Peñalver-Soler, Natalia Campillo and Pilar Viñas

Toxins 2020, 12(1), 51; https://doi.org/10.3390/toxins12010051 - 15 Jan 2020

Cited by 20 | Viewed by 4036

Abstract

Dispersive magnetic solid-phase extraction (DMSPE) has received growing attention for sample treatment preconcentration prior to the separation of analytes due to its many advantages. In the present work, the potential of DMSPE for the determination of emergent mycotoxins (enniatins A, A1, B and [...] Read more.

Dispersive magnetic solid-phase extraction (DMSPE) has received growing attention for sample treatment preconcentration prior to the separation of analytes due to its many advantages. In the present work, the potential of DMSPE for the determination of emergent mycotoxins (enniatins A, A1, B and B1, and beauvericin) is investigated for the first time. Different magnetic nanoparticles were tested and a magnetic multiwalled carbon nanotube (Fe₃O₄@MWCNT) composite was selected for the extraction and preconcentration of the five target mycotoxins in human urine samples before their analysis by ultrahigh performance liquid chromatography coupled to high resolution mass spectrometry (UHPLC-HRMS). The nanocomposite was characterized by energy dispersive X-ray spectrometry, scanning electron microscopy, Fourier transform infrared spectrophotometry, and X-ray diffraction. Several parameters affecting the adsorption and desorption of DMSPE steps were optimized and the method was fully validated. Due to a matrix effect, matrix-matched calibration curves were necessary to carry out quantification. In this way, limits of quantification of between 0.04 and 0.1 μg/L, relative standard deviation values lower than 12% and recoveries between 89.3% and 98.9% were obtained. Finally, a study of the reuse of the Fe₃O₄@MWCNT composite was carried out, confirming that it can be reused at least four times. Full article

(This article belongs to the Special Issue Application of LC-MS/MS in the Mycotoxins Studies)

► Show Figures

Graphical abstract

13 pages, 742 KiB

Open AccessEditor’s ChoiceArticle

Degradation of Aflatoxin B₁ by a Sustainable Enzymatic Extract from Spent Mushroom Substrate of Pleurotus eryngii

by Maria Teresa Branà, Lucrezia Sergio, Miriam Haidukowski, Antonio F. Logrieco and Claudio Altomare

Toxins 2020, 12(1), 49; https://doi.org/10.3390/toxins12010049 - 14 Jan 2020

Cited by 46 | Viewed by 5883

Abstract

Ligninolytic enzymes from white-rot fungi, such as laccase (Lac) and Mn-peroxidase (MnP), are able to degrade aflatoxin B₁ (AFB1), the most harmful among the known mycotoxins. The high cost of purification of these enzymes has limited their implementation into practical technologies. Every [...] Read more.

Ligninolytic enzymes from white-rot fungi, such as laccase (Lac) and Mn-peroxidase (MnP), are able to degrade aflatoxin B₁ (AFB1), the most harmful among the known mycotoxins. The high cost of purification of these enzymes has limited their implementation into practical technologies. Every year, tons of spent mushroom substrate (SMS) are produced as a by-product of edible mushroom cultivation, such as Pleurotus spp., and disposed at a cost for farmers. SMS may still bea source of ligninolytic enzymes useful for AFB1 degradation. The in vitro AFB1-degradative activity of an SMS crude extract (SMSE) was investigated. Results show that: (1) in SMSE, high Lac activity (4 U g⁻¹ dry matter) and low MnP activity (0.4 U g⁻¹ dry matter) were present; (2) after 1 d of incubation at 25 °C, the SMSE was able to degrade more than 50% of AFB1, whereas after 3 and 7 d of incubation, the percentage of degradation reached the values of 75% and 90%, respectively; (3) with increasing pH values, the degradation percentage increased, reaching 90% after 3 d at pH 8. Based on these results, SMS proved to be a suitable source of AFB1 degrading enzymes and the use of SMSE to detoxify AFB1 contaminated commodities appears conceivable. Full article

► Show Figures

Figure 1

16 pages, 6490 KiB

Open AccessEditor’s ChoiceArticle

T-2 Toxin-Induced Oxidative Stress Leads to Imbalance of Mitochondrial Fission and Fusion to Activate Cellular Apoptosis in the Human Liver 7702 Cell Line

by Junhua Yang, Wenbo Guo, Jianhua Wang, Xianli Yang, Zhiqi Zhang and Zhihui Zhao

Toxins 2020, 12(1), 43; https://doi.org/10.3390/toxins12010043 - 10 Jan 2020

Cited by 49 | Viewed by 5358

Abstract

T-2 toxin, as a highly toxic mycotoxin to humans and animals, induces oxidative stress and apoptosis in various cells and tissues. Apoptosis and mitochondrial fusion/fission are two tightly interconnected processes that are crucial for maintaining physiological homeostasis. However, the role of mitochondrial fusion/fission [...] Read more.

T-2 toxin, as a highly toxic mycotoxin to humans and animals, induces oxidative stress and apoptosis in various cells and tissues. Apoptosis and mitochondrial fusion/fission are two tightly interconnected processes that are crucial for maintaining physiological homeostasis. However, the role of mitochondrial fusion/fission in apoptosis of T-2 toxin remains unknown. Hence, we aimed to explore the putative role of mitochondrial fusion/fission on T-2 toxin induced apoptosis in normal human liver (HL-7702) cells. T-2 toxin treatment (0, 0.1, 1.0, or 10 μg/L) for 24 h caused decreased cell viability and ATP concentration and increased production of (ROS), as seen by a loss of mitochondrial membrane potential (∆Ψm) and increase in mitochondrial fragmentation. Subsequently, the mitochondrial dynamic imbalance was activated, evidenced by a dose-dependent decrease and increase in the protein expression of mitochondrial fusion (OPA1, Mfn1, and Mfn2) and fission (Drp1 and Fis1), respectively. Furthermore, the T-2 toxin promoted the release of cytochrome c from mitochondria to cytoplasm and induced cell apoptosis triggered by upregulation of Bax and Bax/Bcl-2 ratios, and further activated the caspase pathways. Taken together, these results indicate that altered mitochondrial dynamics induced by oxidative stress with T-2 toxin exposure likely contribute to mitochondrial injury and HL-7702 cell apoptosis. Full article

► Show Figures

Graphical abstract

19 pages, 2734 KiB

Open AccessEditor’s ChoiceArticle

Comprehensive Evaluation of the Efficiency of Yeast Cell Wall Extract to Adsorb Ochratoxin A and Mitigate Accumulation of the Toxin in Broiler Chickens

by Suvi Vartiainen, Alexandros Yiannikouris, Juha Apajalahti and Colm A. Moran

Toxins 2020, 12(1), 37; https://doi.org/10.3390/toxins12010037 - 7 Jan 2020

Cited by 22 | Viewed by 4678

Abstract

Ochratoxin A (OTA) is a common mycotoxin contaminant in animal feed. When absorbed from the gastrointestinal tract, OTA has a propensity for pathological effects on animal health and deposition in animal tissues. In this study, the potential of yeast cell wall extracts (YCWE) [...] Read more.

Ochratoxin A (OTA) is a common mycotoxin contaminant in animal feed. When absorbed from the gastrointestinal tract, OTA has a propensity for pathological effects on animal health and deposition in animal tissues. In this study, the potential of yeast cell wall extracts (YCWE) to adsorb OTA was evaluated using an in vitro method in which consecutive animal digestion events were simulated. Low pH markedly increased OTA binding to YCWE, which was reversed with a pH increased to 6.5. Overall, in vitro analysis revealed that 30% of OTA was adsorbed to YCWE. Additional computational molecular modelling revealed that change in pH alters the OTA charge and modulates the interaction with the YCWE β-d-glucans. The effectiveness of YCWE was tested in a 14-day broiler chicken trial. Birds were subjected to five dietary treatments; with and without OTA, and OTA combined with YCWE at three dosages. At the end of the trial, liver OTA deposition was evaluated. Data showed a decrease of up to 30% in OTA deposits in the liver of broilers fed both OTA and YCWE. In the case of OTA, a tight correlation between the mitigation efficacy of YCWE between in vitro and in vivo model could be observed. Full article

(This article belongs to the Special Issue Mycotoxin Exposure and Related Diseases)

► Show Figures

Figure 1

26 pages, 1038 KiB

Open AccessEditor’s ChoiceReview

Natural Sources and Bioactivities of 2,4-Di-Tert-Butylphenol and Its Analogs

by Fuqiang Zhao, Ping Wang, Rima D. Lucardi, Zushang Su and Shiyou Li

Toxins 2020, 12(1), 35; https://doi.org/10.3390/toxins12010035 - 6 Jan 2020

Cited by 217 | Viewed by 14046

Abstract

2,4-Di-tert-butylphenol or 2,4-bis(1,1-dimethylethyl)-phenol (2,4-DTBP) is a common toxic secondary metabolite produced by various groups of organisms. The biosources and bioactivities of 2,4-DTBP have been well investigated, but the phenol has not been systematically reviewed. This article provides a comprehensive review of 2,4-DTBP and [...] Read more.

2,4-Di-tert-butylphenol or 2,4-bis(1,1-dimethylethyl)-phenol (2,4-DTBP) is a common toxic secondary metabolite produced by various groups of organisms. The biosources and bioactivities of 2,4-DTBP have been well investigated, but the phenol has not been systematically reviewed. This article provides a comprehensive review of 2,4-DTBP and its analogs with emphasis on natural sources and bioactivities. 2,4-DTBP has been found in at least 169 species of bacteria (16 species, 10 families), fungi (11 species, eight families), diatom (one species, one family), liverwort (one species, one family), pteridiphyta (two species, two families), gymnosperms (four species, one family), dicots (107 species, 58 families), monocots (22 species, eight families), and animals (five species, five families). 2,4-DTBP is often a major component of violate or essential oils and it exhibits potent toxicity against almost all testing organisms, including the producers; however, it is not clear why organisms produce autotoxic 2,4-DTBP and its analogs. The accumulating evidence indicates that the endocidal regulation seems to be the primary function of the phenols in the producing organisms. Full article

(This article belongs to the Collection Toxic and Pharmacological Effect of Plant Toxins)

► Show Figures

Figure 1

14 pages, 820 KiB

Open AccessEditor’s ChoiceReview

Botulinum Neurotoxins and Cancer—A Review of the Literature

by Shivam O. Mittal and Bahman Jabbari

Toxins 2020, 12(1), 32; https://doi.org/10.3390/toxins12010032 - 5 Jan 2020

Cited by 35 | Viewed by 7549

Abstract

Botulinum neurotoxins (BoNT) possess an analgesic effect through several mechanisms including an inhibition of acetylcholine release from the neuromuscular junction as well as an inhibition of specific pain transmitters and mediators. Animal studies have shown that a peripheral injection of BoNTs impairs the [...] Read more.

Botulinum neurotoxins (BoNT) possess an analgesic effect through several mechanisms including an inhibition of acetylcholine release from the neuromuscular junction as well as an inhibition of specific pain transmitters and mediators. Animal studies have shown that a peripheral injection of BoNTs impairs the release of major pain transmitters such as substance P, calcitonin gene related peptide (CGRP) and glutamate from peripheral nerve endings as well as peripheral and central neurons (dorsal root ganglia and spinal cord). These effects lead to pain relief via the reduction of peripheral and central sensitization both of which reflect important mechanisms of pain chronicity. This review provides updated information about the effect of botulinum toxin injection on local pain caused by cancer, painful muscle spasms from a remote cancer, and pain at the site of cancer surgery and radiation. The data from the literature suggests that the local injection of BoNTs improves muscle spasms caused by cancerous mass lesions and alleviates the post-operative neuropathic pain at the site of surgery and radiation. It also helps repair the parotid damage (fistula, sialocele) caused by facial surgery and radiation and improves post-parotidectomy gustatory hyperhidrosis. The limited literature that suggests adding botulinum toxins to cell culture slows/halts the growth of certain cancer cells is also reviewed and discussed. Full article

(This article belongs to the Special Issue Toxins and Cancer Therapy)

► Show Figures

Figure 1

14 pages, 1783 KiB

Open AccessEditor’s ChoiceArticle

Occurrence and Characterization of Fungi and Mycotoxins in Contaminated Medicinal Herbs

by Ling Chen, Weipeng Guo, Yuqing Zheng, Jinzhen Zhou, Tingting Liu, Wei Chen, Daqing Liang, Meiping Zhao, Yudan Zhu, Qingping Wu and Jumei Zhang

Toxins 2020, 12(1), 30; https://doi.org/10.3390/toxins12010030 - 3 Jan 2020

Cited by 55 | Viewed by 10149

Abstract

Traditional medicinal herbs are widely used and may be contaminated with mycotoxigenic fungi during cultivation, harvesting, and storage, causing spoilage and mycotoxin production. We evaluated the predominant mycoflora and extent of mycotoxin contaminations in 48 contaminated samples of 13 different medicinal herbs. In [...] Read more.

Traditional medicinal herbs are widely used and may be contaminated with mycotoxigenic fungi during cultivation, harvesting, and storage, causing spoilage and mycotoxin production. We evaluated the predominant mycoflora and extent of mycotoxin contaminations in 48 contaminated samples of 13 different medicinal herbs. In total, 70.8% of herbs were slightly contaminated with aflatoxins (<5 μg kg⁻¹). Codonopsis radix samples contained ochratoxin A (OTA) (360–515 μg kg⁻¹), and Scutellariae radix samples contained OTA (49–231 μg kg⁻¹) and citrinin (15–53 μg kg⁻¹). Forty samples (83.3%) contained fungal contamination. Sixty-nine strains were characterized via morphological and molecular identification. The predominant mycoflora comprised four genera, Aspergillus spp. (26.1%), Penicillium spp. (24.6%), Rhizopus spp. (14.5%), and Trichoderma spp. (11.6%). Aflatoxins, OTA, and citrinin were detected in 37 cultures by high-performance liquid chromatography-tandem mass spectrometry. Approximately 21.6% of Aspergillus and Penicillium isolates produced mycotoxins. One Penicillium polonicum strain isolated from Scutellariae radix synthesized citrinin. Multiplex PCR analysis showed that three Aspergillus flavus strains harbored aflatoxin biosynthesis genes. One Aspergillus flavus strain isolated from Amomi fructus produced AFB₁ and AFB₂. To the best of our knowledge, the citrinin production by Aspergillus chevalieri and Penicillium sacculum was first reported in this study, which poses a potential risk of mycotoxin contamination in medicinal herbs. Full article

(This article belongs to the Section Mycotoxins)

► Show Figures

Figure 1

21 pages, 1574 KiB

Open AccessEditor’s ChoiceReview

Control of Aflatoxigenic Molds by Antagonistic Microorganisms: Inhibitory Behaviors, Bioactive Compounds, Related Mechanisms, and Influencing Factors

by Xianfeng Ren, Qi Zhang, Wen Zhang, Jin Mao and Peiwu Li

Toxins 2020, 12(1), 24; https://doi.org/10.3390/toxins12010024 - 1 Jan 2020

Cited by 65 | Viewed by 7096

Abstract

Aflatoxin contamination has been causing great concern worldwide due to the major economic impact on crop production and their toxicological effects to human and animals. Contamination can occur in the field, during transportation, and also in storage. Post-harvest contamination usually derives from the [...] Read more.

Aflatoxin contamination has been causing great concern worldwide due to the major economic impact on crop production and their toxicological effects to human and animals. Contamination can occur in the field, during transportation, and also in storage. Post-harvest contamination usually derives from the pre-harvest infection of aflatoxigenic molds, especially aflatoxin-producing Aspergilli such as Aspergillus flavus and A. parasiticus. Many strategies preventing aflatoxigenic molds from entering food and feed chains have been reported, among which biological control is becoming one of the most praised strategies. The objective of this article is to review the biocontrol strategy for inhibiting the growth of and aflatoxin production by aflatoxigenic fungi. This review focuses on comparing inhibitory behaviors of different antagonistic microorganisms including various bacteria, fungi and yeasts. We also reviewed the bioactive compounds produced by microorganisms and the mechanisms leading to inhibition. The key factors influencing antifungal activities of antagonists are also discussed in this review. Full article

► Show Figures

Figure 1

16 pages, 2816 KiB

Open AccessEditor’s ChoiceArticle

Phytotoxic Responses of Soybean (Glycine max L.) to Botryodiplodin, a Toxin Produced by the Charcoal Rot Disease Fungus, Macrophomina phaseolina

by Hamed K. Abbas, Nacer Bellaloui, Alemah M. Butler, Justin L. Nelson, Mohamed Abou-Karam and W. Thomas Shier

Toxins 2020, 12(1), 25; https://doi.org/10.3390/toxins12010025 - 1 Jan 2020

Cited by 30 | Viewed by 5189

Abstract

Toxins have been proposed to facilitate fungal root infection by creating regions of readily-penetrated necrotic tissue when applied externally to intact roots. Isolates of the charcoal rot disease fungus, Macrophomina phaseolina, from soybean plants in Mississippi produced a phytotoxic toxin, (−)-botryodiplodin, but [...] Read more.

Toxins have been proposed to facilitate fungal root infection by creating regions of readily-penetrated necrotic tissue when applied externally to intact roots. Isolates of the charcoal rot disease fungus, Macrophomina phaseolina, from soybean plants in Mississippi produced a phytotoxic toxin, (−)-botryodiplodin, but no detectable phaseolinone, a toxin previously proposed to play a role in the root infection mechanism. This study was undertaken to determine if (−)-botryodiplodin induces toxic responses of the types that could facilitate root infection. (±)-Botryodiplodin prepared by chemical synthesis caused phytotoxic effects identical to those observed with (−)-botryodiplodin preparations from M. phaseolina culture filtrates, consistent with fungus-induced phytotoxicity being due to (−)-botryodiplodin, not phaseolinone or other unknown impurities. Soybean leaf disc cultures of Saline cultivar were more susceptible to (±)-botryodiplodin phytotoxicity than were cultures of two charcoal rot-resistant genotypes, DS97-84-1 and DT97-4290. (±)-Botryodiplodin caused similar phytotoxicity in actively growing duckweed (Lemna pausicostata) plantlet cultures, but at much lower concentrations. In soybean seedlings growing in hydroponic culture, (±)-botryodiplodin added to culture medium inhibited lateral and tap root growth, and caused loss of root caps and normal root tip cellular structure. Thus, botryodiplodin applied externally to undisturbed soybean roots induced phytotoxic responses of types expected to facilitate fungal root infection. Full article

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

► Show Figures

Figure 1

Journal Menu

Journal Browser

Editor’s Choice Articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI