Toxins

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3 pages, 212 KiB

Open AccessEditorial

Introduction to the Toxins Special Issue on Toxicological Effects of Mycotoxin on Target Cells

by Ana Juan-García

Toxins 2020, 12(7), 446; https://doi.org/10.3390/toxins12070446 - 10 Jul 2020

Cited by 1 | Viewed by 2167

Abstract

Mycotoxins are toxic secondary metabolites produced by filamentous fungi from Fusarium, Alternaria and Penicillium spp [...] Full article

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

Research

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13 pages, 3818 KiB

Open AccessEditor’s ChoiceArticle

Deoxynivalenol Induces Inflammation in IPEC-J2 Cells by Activating P38 Mapk And Erk1/2

by Hua Zhang, Xiwen Deng, Chuang Zhou, Wenda Wu and Haibin Zhang

Toxins 2020, 12(3), 180; https://doi.org/10.3390/toxins12030180 - 13 Mar 2020

Cited by 50 | Viewed by 4771

Abstract

Fusarium-derived mycotoxin deoxynivalenol (DON) usually induces diarrhea, vomiting and gastrointestinal inflammation. We studied the cytotoxic effect of DON on porcine small intestinal epithelium using the intestinal porcine epithelial cell line IPEC-J2. We screened out differentially expressed genes (DEGs) using RNA-seq and identified 320 [...] Read more.

Fusarium-derived mycotoxin deoxynivalenol (DON) usually induces diarrhea, vomiting and gastrointestinal inflammation. We studied the cytotoxic effect of DON on porcine small intestinal epithelium using the intestinal porcine epithelial cell line IPEC-J2. We screened out differentially expressed genes (DEGs) using RNA-seq and identified 320 upregulated genes and 160 downregulated genes. The enrichment pathways of these DEGs focused on immune-related pathways. DON induced proinflammatory gene expression, including cytokines, chemokines and other inflammation-related genes. DON increased IL1A, IL6 and TNF-α release and DON activated the phosphorylation of extracellular signal-regulated kinase-1 and-2 (ERK1/2), JUN N-terminal kinase (JNK) and p38 MAPK. A p38 inhibitor attenuated DON-induced IL6, TNF-α, CXCL2, CXCL8, IL12A, IL1A, CCL20, CCL4 and IL15 production, while an ERK1/2 inhibitor had only a small inhibitory effect on IL15 and IL6. An inhibitor of p38 MAPK decreased the release of IL1A, IL6 and TNF-α and an inhibitor of ERK1/2 partly attenuated protein levels of IL6. These data demonstrate that DON induces proinflammatory factor production in IPEC-J2 cells by activating p38 and ERK1/2. Full article

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

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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 36 | Viewed by 5415

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)

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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 53 | Viewed by 4184

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)

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18 pages, 3665 KiB

Open AccessArticle

Transcriptome Analysis of Ochratoxin A-Induced Apoptosis in Differentiated Caco-2 Cells

by Xue Yang, Yanan Gao, Qiaoyan Yan, Xiaoyu Bao, Shengguo Zhao, Jiaqi Wang and Nan Zheng

Toxins 2020, 12(1), 23; https://doi.org/10.3390/toxins12010023 - 31 Dec 2019

Cited by 17 | Viewed by 4030

Abstract

Ochratoxin A (OTA), an important mycotoxin that occurs in food and animal feed, has aroused widespread concern in recent years. Previous studies have indicated that OTA causes nephrotoxicity, hepatotoxicity, genotoxicity, immunotoxicity, cytotoxicity, and neurotoxicity. The intestinal toxicity of OTA has gradually become a [...] Read more.

Ochratoxin A (OTA), an important mycotoxin that occurs in food and animal feed, has aroused widespread concern in recent years. Previous studies have indicated that OTA causes nephrotoxicity, hepatotoxicity, genotoxicity, immunotoxicity, cytotoxicity, and neurotoxicity. The intestinal toxicity of OTA has gradually become a focus of research, but the mechanisms underlying this toxicity have not been described. Here, differentiated Caco-2 cells were incubated for 48 h with different concentrations of OTA and transcriptome analysis was used to estimate damage to the intestinal barrier. Gene expression profiling was used to compare the characteristics of differentially expressed genes (DEGs). There were altogether 10,090 DEGs, mainly clustered into two downregulation patterns. The Search Tool for Retrieval of Interacting Genes (STRING), which was used to analyze the protein–protein interaction network, indicated that 24 key enzymes were mostly responsible for regulating cell apoptosis. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis was used to validate eight genes, three of which were key genes (CASP3, CDC25B, and EGR1). The results indicated that OTA dose-dependently induces apoptosis in differentiated Caco-2 cells. Transcriptome analysis showed that the impairment of intestinal function caused by OTA might be partly attributed to apoptosis, which is probably associated with downregulation of murine double minute 2 (MDM2) expression and upregulation of Noxa and caspase 3 (CASP3) expression. This study has highlighted the intestinal toxicity of OTA and provided a genome-wide view of biological responses, which provides a theoretical basis for enterotoxicity and should be useful in establishing a maximum residue limit for OTA. Full article

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

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12 pages, 1969 KiB

Open AccessArticle

Reduced Toxicity of Trichothecenes, Isotrichodermol, and Deoxynivalenol, by Transgenic Expression of the Tri101 3-O-Acetyltransferase Gene in Cultured Mammalian FM3A Cells

by Nozomu Tanaka, Ryo Takushima, Akira Tanaka, Ayaki Okada, Kosuke Matsui, Kazuyuki Maeda, Shunichi Aikawa, Makoto Kimura and Naoko Takahashi-Ando

Toxins 2019, 11(11), 654; https://doi.org/10.3390/toxins11110654 - 10 Nov 2019

Cited by 7 | Viewed by 3219

Abstract

In trichothecene-producing fusaria, isotrichodermol (ITDol) is the first intermediate with a trichothecene skeleton. In the biosynthetic pathway of trichothecene, a 3-O-acetyltransferase, encoded by Tri101, acetylates ITDol to a less-toxic intermediate, isotrichodermin (ITD). Although trichothecene resistance has been conferred to microbes [...] Read more.

In trichothecene-producing fusaria, isotrichodermol (ITDol) is the first intermediate with a trichothecene skeleton. In the biosynthetic pathway of trichothecene, a 3-O-acetyltransferase, encoded by Tri101, acetylates ITDol to a less-toxic intermediate, isotrichodermin (ITD). Although trichothecene resistance has been conferred to microbes and plants transformed with Tri101, there are no reports of resistance in cultured mammalian cells. In this study, we found that a 3-O-acetyl group of trichothecenes is liable to hydrolysis by esterases in fetal bovine serum and FM3A cells. We transfected the cells with Tri101 under the control of the MMTV-LTR promoter and obtained a cell line G3 with the highest level of C-3 acetylase activity. While the wild-type FM3A cells hardly grew in the medium containing 0.40 μM ITDol, many G3 cells survived at this concentration. The IC₅₀ values of ITDol and ITD in G3 cells were 1.0 and 9.6 μM, respectively, which were higher than the values of 0.23 and 3.0 μM in the wild-type FM3A cells. A similar, but more modest, tendency was observed in deoxynivalenol and 3-acetyldeoxynivalenol. Our findings indicate that the expression of Tri101 conferred trichothecene resistance in cultured mammalian cells. Full article

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

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20 pages, 2000 KiB

Open AccessEditor’s ChoiceArticle

Twenty-Eight Fungal Secondary Metabolites Detected in Pig Feed Samples: Their Occurrence, Relevance and Cytotoxic Effects In Vitro

by Barbara Novak, Valentina Rainer, Michael Sulyok, Dietmar Haltrich, Gerd Schatzmayr and Elisabeth Mayer

Toxins 2019, 11(9), 537; https://doi.org/10.3390/toxins11090537 - 14 Sep 2019

Cited by 22 | Viewed by 5006

Abstract

Feed samples are frequently contaminated by a wide range of chemically diverse natural products, which can be determined using highly sensitive analytical techniques. Next to already well-investigated mycotoxins, unknown or unregulated fungal secondary metabolites have also been found, some of which at significant [...] Read more.

Feed samples are frequently contaminated by a wide range of chemically diverse natural products, which can be determined using highly sensitive analytical techniques. Next to already well-investigated mycotoxins, unknown or unregulated fungal secondary metabolites have also been found, some of which at significant concentrations. In our study, 1141 pig feed samples were analyzed for more than 800 secondary fungal metabolites using the same LC-MS/MS method and ranked according to their prevalence. Effects on the viability of the 28 most relevant were tested on an intestinal porcine epithelial cell line (IPEC-J2). The most frequently occurring compounds were determined as being cyclo-(L-Pro-L-Tyr), moniliformin, and enniatin B, followed by enniatin B1, aurofusarin, culmorin, and enniatin A1. The main mycotoxins, deoxynivalenol and zearalenone, were found only at ranks 8 and 10. Regarding cytotoxicity, apicidin, gliotoxin, bikaverin, and beauvericin led to lower IC₅₀ values, between 0.52 and 2.43 µM, compared to deoxynivalenol (IC₅₀ = 2.55 µM). Significant cytotoxic effects were also seen for the group of enniatins, which occurred in up to 82.2% of the feed samples. Our study gives an overall insight into the amount of fungal secondary metabolites found in pig feed samples compared to their cytotoxic effects in vitro. Full article

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

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14 pages, 1275 KiB

Open AccessEditor’s ChoiceArticle

Cytotoxicity, Genotoxicity and Disturbance of Cell Cycle in HepG2 Cells Exposed to OTA and BEA: Single and Combined Actions

by Ana Juan-García, Josefa Tolosa, Cristina Juan and María-José Ruiz

Toxins 2019, 11(6), 341; https://doi.org/10.3390/toxins11060341 - 14 Jun 2019

Cited by 49 | Viewed by 4564

Abstract

Mycotoxins are produced by a number of fungal genera spp., for example, Aspergillus, Penicillium, Alternaria, Fusarium, and Claviceps. Beauvericin (BEA) and Ochratoxin A (OTA) are present in various cereal crops and processed grains. This goal of this study [...] Read more.

Mycotoxins are produced by a number of fungal genera spp., for example, Aspergillus, Penicillium, Alternaria, Fusarium, and Claviceps. Beauvericin (BEA) and Ochratoxin A (OTA) are present in various cereal crops and processed grains. This goal of this study was to determine their combination effect in HepG2 cells, presented for the first time. In this study, the type of interaction among BEA and OTA through an isobologram method, cell cycle disturbance by flow cytometry, and genotoxic potential by in vitro micronucleus (MN) assay following the TG 487 (OECD, 2016) of BEA and OTA individually and combined in HepG2 cells are presented. Cytotoxic concentration ranges studied by the MTT assay over 24, 48, and 72 h were from 0 to 25 µM for BEA and from 0 to 100 µM for OTA, while BEA + OTA combinations were at a 1:10 ratio from 3.4 to 27.5 µM. The toxicity observed for BEA was higher than for OTA at all times assayed; additive and synergistic effects were detected for their mixtures. Cell cycle arrest in the G0/G1 phase was detected for OTA and BEA + OTA treatments in HepG2 cells. Genotoxicity revealed significant effects for BEA, OTA, and in combinations underlining the importance of studying real exposure scenarios of chronic exposure to mycotoxins. Full article

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

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11 pages, 4020 KiB

Open AccessEditor’s ChoiceArticle

Comparison of Apoptosis and Autophagy in Human Chondrocytes Induced by the T-2 and HT-2 Toxins

by Fang-Fang Yu, Xia-Lu Lin, Xi Wang, Zhi-Guang Ping and Xiong Guo

Toxins 2019, 11(5), 260; https://doi.org/10.3390/toxins11050260 - 8 May 2019

Cited by 27 | Viewed by 3778

Abstract

In this report, we have investigated the apoptosis and autophagy of chondrocytes induced by the T-2 and HT-2 toxins. The viability of chondrocytes was measured by the MTT assay. Malondialdehyde (MDA) and superoxide dismutase (SOD) kits were used to measure the oxidative stress [...] Read more.

In this report, we have investigated the apoptosis and autophagy of chondrocytes induced by the T-2 and HT-2 toxins. The viability of chondrocytes was measured by the MTT assay. Malondialdehyde (MDA) and superoxide dismutase (SOD) kits were used to measure the oxidative stress of chondrocytes. The apoptosis of chondrocytes was measured using flow cytometry. Hoechst 33258 and MDC staining agents were introduced to analyze apoptosis and autophagy induction in chondrocytes, respectively. Protein expression of Bax, caspase-9, caspase-3, and Beclin1 was examined by western blotting analysis. The T-2 and HT-2 toxins significantly decreased the viability of chondrocytes in a time-dependent manner. The level of oxidative stress in chondrocytes induced by the T-2 toxin was significantly higher when compared with that of the HT-2 toxin. The apoptosis rate of chondrocytes induced by the T-2 toxin increased from 3.26 ± 1.03%, 18.38 ± 1.28%, 34.5 ± 1.40% to 49.67 ± 5.31%, whereas apoptosis rate of chondrocytes induced by the HT-2 toxin increased from 3.82 ± 1.03%, 11.61 ± 1.27%, 25.72 ± 2.95% to 36.28 ± 2.81% in 48 h incubation time. Hoechst 33258 staining confirmed that apoptosis of chondrocytes induced by the T-2 toxin was significantly higher than that observed when the chondrocytes were incubated with the HT-2 toxin. MDC staining revealed that the autophagy rate of chondrocytes induced by the T-2 toxin increased from 6.38% to 63.02%, whereas this rate induced by the HT-2 toxin changed from 6.08% to 53.33%. The expression levels of apoptosis and autophagy related proteins, Bax, caspase-9, caspase-3, and Beclin1 in chondrocytes induced by the T-2 toxin were significantly higher when compared with those levels induced by the HT-2 toxin. Full article

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

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11 pages, 6386 KiB

Open AccessArticle

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

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

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

Cited by 21 | Viewed by 5512

Abstract

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

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

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

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10 pages, 1923 KiB

Open AccessArticle

BmTudor-sn Is a Binding Protein of Destruxin A in Silkworm Bm12 Cells

by Jingjing Wang, Weina Hu and Qiongbo Hu

Toxins 2019, 11(2), 67; https://doi.org/10.3390/toxins11020067 - 24 Jan 2019

Cited by 12 | Viewed by 3081

Abstract

Destruxin A (DA), a hexa-cyclodepsipeptidic mycotoxin secreted by the entomopathogenic fungus Metarhizium anisopliae, was reported to have an insecticidal effect and anti-immunity activity. However, its molecular mechanism of action remains unclear. Previously, we isolated several potential DA-affinity (binding) proteins in the Bombyx [...] Read more.

Destruxin A (DA), a hexa-cyclodepsipeptidic mycotoxin secreted by the entomopathogenic fungus Metarhizium anisopliae, was reported to have an insecticidal effect and anti-immunity activity. However, its molecular mechanism of action remains unclear. Previously, we isolated several potential DA-affinity (binding) proteins in the Bombyx mori Bm12 cell line. By docking score using MOE2015, we selected three proteins—BmTudor-sn, BmPiwi, and BmAGO2—for further validation. First, using Bio-Layer Interferometry in vitro, we found that BmTudor-sn had an affinity interaction with DA at 125, 250, and 500 µM, while BmPiwi and BmAGO2 had no interaction signal with DA. Second, we employed standard immunoblotting to verify that BmTudor-sn is susceptible to DA, but BmPiwi and BmAGO2 are not. Third, to verify these findings in vivo, we used a target engagement strategy based on shifts in protein thermal stability following ligand binding termed the cellular thermal shift assay and found no thermal stability shift in BmPiwi and BmAGO2, whereas a shift was found for BmTudor-sn. In addition, in BmTudor-sn knockdown Bm12 cells, we observed that cell viability increased under DA treatment. Furthermore, insect two-hybrid system results indicated that the key site involved in DA binding to BmTudor-sn was Leu704. In conclusion, in vivo and in vitro experimental evidence indicated that BmTudor-sn is a binding protein of DA in silkworm Bm12 cells at the 100 µM level, and the key site of this interaction is Leu704. Our results provide new perspectives to aid in elucidating the molecular mechanism of action of DA in insects and developing new biopesticide. Full article

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

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Review

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24 pages, 1093 KiB

Open AccessEditor’s ChoiceReview

Assessing the Effect of Mycotoxin Combinations: Which Mathematical Model Is (the Most) Appropriate?

by Domagoj Kifer, Daniela Jakšić and Maja Šegvić Klarić

Toxins 2020, 12(3), 153; https://doi.org/10.3390/toxins12030153 - 29 Feb 2020

Cited by 31 | Viewed by 3575

Abstract

In the past decades, many studies have examined the nature of the interaction between mycotoxins in biological models classifying interaction effects as antagonisms, additive effects, or synergisms based on a comparison of the observed effect with the expected effect of combination. Among several [...] Read more.

In the past decades, many studies have examined the nature of the interaction between mycotoxins in biological models classifying interaction effects as antagonisms, additive effects, or synergisms based on a comparison of the observed effect with the expected effect of combination. Among several described mathematical models, the arithmetic definition of additivity and factorial analysis of variance were the most commonly used in mycotoxicology. These models are incorrectly based on the assumption that mycotoxin dose-effect curves are linear. More appropriate mathematical models for assessing mycotoxin interactions include Bliss independence, Loewe’s additivity law, combination index, and isobologram analysis, Chou-Talalays median-effect approach, response surface, code for the identification of synergism numerically efficient (CISNE) and MixLow method. However, it seems that neither model is ideal. This review discusses the advantages and disadvantages of these mathematical models. Full article

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

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26 pages, 4727 KiB

Open AccessEditor’s ChoiceReview

Tremorgenic Mycotoxins: Structure Diversity and Biological Activity

by Priyanka Reddy, Kathryn Guthridge, Simone Vassiliadis, Joanne Hemsworth, Inoka Hettiarachchige, German Spangenberg and Simone Rochfort

Toxins 2019, 11(5), 302; https://doi.org/10.3390/toxins11050302 - 27 May 2019

Cited by 54 | Viewed by 6446

Abstract

Indole-diterpenes are an important class of chemical compounds which can be unique to different fungal species. The highly complex lolitrem compounds are confined to Epichloë species, whilst penitrem production is confined to Penicillium spp. and Aspergillus spp. These fungal species are often present [...] Read more.

Indole-diterpenes are an important class of chemical compounds which can be unique to different fungal species. The highly complex lolitrem compounds are confined to Epichloë species, whilst penitrem production is confined to Penicillium spp. and Aspergillus spp. These fungal species are often present in association with pasture grasses, and the indole-diterpenes produced may cause toxicity in grazing animals. In this review, we highlight the unique structural variations of indole-diterpenes that are characterised into subgroups, including paspaline, paxilline, shearinines, paspalitrems, terpendoles, penitrems, lolitrems, janthitrems, and sulpinines. A detailed description of the unique biological activities has been documented where even structurally related compounds have displayed unique biological activities. Indole-diterpene production has been reported in two classes of ascomycete fungi, namely Eurotiomycetes (e.g., Aspergillus and Penicillium) and Sordariomycetes (e.g., Claviceps and Epichloë). These compounds all have a common structural core comprised of a cyclic diterpene skeleton derived from geranylgeranyl diphosphate (GGPP) and an indole moiety derived from tryptophan. Structure diversity is generated from the enzymatic conversion of different sites on the basic indole-diterpene structure. This review highlights the wide-ranging biological versatility presented by the indole-diterpene group of compounds and their role in an agricultural and pharmaceutical setting. Full article

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

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