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1.
Arh Hig Rada Toksikol ; 72(3): 173-181, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34587668

RESUMO

Some mycotoxins such as beauvericin (BEA), ochratoxin A (OTA), and zearalenone (ZEA) can cross the blood brain barrier, which is why we tested the anti-inflammatory action of a pumpkin carotenoid extract (from the pulp) against these mycotoxins and their combinations (OTA+ZEA and OTA+ZEA+BEA) on a blood brain barrier model with co-cultured ECV304 and C6 cells using an untargeted metabolomic approach. The cells were added with mycotoxins at a concentration of 100 nmol/L per mycotoxin and pumpkin carotenoid extract at 500 nmol/L. For control we used only vehicle solvent (cell control) or vehicle solvent with pumpkin extract (extract control). After two hours of exposure, samples were analysed with HPLC-ESI-QTOF-MS. Metabolites were identified against the Metlin database. The proinflammatory arachidonic acid metabolite eoxin (14,15-LTE4) showed lower abundance in ZEA and BEA+OTA+ZEA-treated cultures that also received the pumpkin extract than in cultures that were not treated with the extract. Another marker of inflammation, prostaglandin D2-glycerol ester, was only found in cultures treated with OTA+ZEA and BEA+OTA+ZEA but not in the ones that were also treated with the pumpkin extract. Furthermore, the concentration of the pumpkin extract metabolite dihydromorelloflavone significantly decreased in the presence of mycotoxins. In conclusion, the pumpkin extract showed protective activity against cellular inflammation triggered by mycotoxins thanks to the properties pertinent to flavonoids contained in the pulp.


Assuntos
Cucurbita , Micotoxinas , Ocratoxinas , Barreira Hematoencefálica , Carotenoides/farmacologia , Micotoxinas/toxicidade , Extratos Vegetais/farmacologia
2.
Nutrients ; 13(8)2021 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-34444698

RESUMO

Maintaining lipid homeostasis is crucial to liver function, the key organ that governs the whole-body energy metabolism. In contrast, lipid dysregulation has been implicated in mycotoxin-induced liver injury, by which the pathophysiological regulation and the molecular components involved remain elusive. Here we focused on the potential roles of orphan nuclear receptor (NR) RORγ in lipid programming, and aimed to explore its action on cholesterol regulation in the liver of mycotoxin-exposed piglets. We found that liver tissues were damaged in the mycotoxin-exposed piglets compared to the healthy controls, revealed by histological analysis, elevated seral ALT, AST and ALP levels, and increased caspase 3/7 activities. Consistent with the transcriptomic finding of down-regulated cholesterol metabolism, we demonstrated that both cholesterol contents and cholesterol biosynthesis/transformation gene expressions in the mycotoxin-exposed livers were reduced, including HMGCS1, FDPS, SQLE, EBP, FDFT1 and VLDLR. Furthermore, we reported that RORγ binds to the cholesterol metabolic genes in porcine hepatocytes using a genome-wide ChIP-seq analysis, whereas mycotoxin decreased the RORγ binding occupancies genome-wide, especially at the cholesterol metabolic pathway. In addition, we revealed the enrichment of co-factors p300 and SRC, the histone marks H3K27ac and H3K4me2, together with RNA Polymerase II (Pol-II) at the locus of HMGCS1 in hepatocytes, which were reduced by mycotoxin-exposure. Our results provide a deep insight into the cholesterol metabolism regulation during mycotoxin-induced liver injury, and propose NRs as therapeutic targets for anti-mycotoxin treatments.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas/genética , Colesterol/genética , Regulação da Expressão Gênica/genética , Metabolismo dos Lipídeos/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/fisiologia , Animais , Modelos Animais de Doenças , Hepatócitos/metabolismo , Homeostase/genética , Fígado/metabolismo , Micotoxinas/toxicidade , Suínos
3.
Chem Biol Interact ; 347: 109614, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34364835

RESUMO

Ochratoxin A (OTA), an important fungal metabolite in foods and feeds has been shown to induce oxidative stress and cellular injuries to human and animal subjects. This study was designed to investigate the mode of action of a biological modifier Trichosporon mycotoxinivorans (TM), against OTA-mediated oxidative stress and tissue toxicity on broiler chickens. The birds were offered diets supplemented with OTA (0.15 and 0.3 mg/kg feed) and/or TM (0.5, 1.0 g/kg) for 42 days of age, and blood and tissue samples were collected to examine the oxidative stress, biochemical and histopathological parameters. Dietary OTA at all the tested levels induced the hepatic and renal tissue injury as indicated by significant decreased total antioxidant capacity in these organs along with significant decreased (p ≤ 0.05) serum concentrations of total proteins and albumin. The serum concentrations of alanine aminotransferase (ALT) and urea were significantly increased, and these observations were further supported by degenerative changes and increased relative weights of liver and kidneys. The dietary supplementation of TM at both tested levels relieved the detrimental impact of 0.15 and 0.3 mg OTA/kg on the studied parameters. The results of the study demonstrated that dietary TM significantly protects broiler chickens by reducing OTA-induced oxidative damage and tissue injury.


Assuntos
Basidiomycota/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/dietoterapia , Suplementos Nutricionais/microbiologia , Nefropatias/dietoterapia , Micotoxinas/toxicidade , Ocratoxinas/toxicidade , Animais , Aspergillus ochraceus , Galinhas , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Micotoxinas/metabolismo , Ocratoxinas/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
4.
Compr Rev Food Sci Food Saf ; 20(5): 4390-4406, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34323368

RESUMO

Alternaria molds are known to cause the contamination of food with their secondary metabolites, a chemically very heterogeneous group of compounds. Yet, after decades of research on the occurrence and the toxicity of Alternaria toxins in academia, no regulation has been implemented yet, thus leaving these potential food contaminants in the status of so-called "emerging mycotoxins". However, research on this topic has been far from static, leading to the European Food Safety Authority repeatedly calling for more data on the occurrence and toxicity of genotoxic metabolites such as alternariol (AOH) and its monomethyl ether (AME). To give an overview on recent developments in the field, this comprehensive review summarizes published data and addresses current challenges arising from the chemical complexity of Alternaria's metabolome, mixture effects and the emergence of novel biological targets like cell membranes or the interaction with different receptors. Besides toxicodynamics, we review recent research on toxicokinetics, including the first in vivo studies which incorporated the rarely investigated-but highly genotoxic-perylene quinones. Furthermore, a particular focus lies on the advances of liquid chromatography/tandem mass spectrometry (LC-MS/MS)-based analytical tools for determining a broader spectrum of Alternaria toxins including modified/masked forms and assessing exposure via human biomonitoring (HBM).


Assuntos
Alternaria , Micotoxinas , Cromatografia Líquida , Contaminação de Alimentos/análise , Humanos , Micotoxinas/toxicidade , Espectrometria de Massas em Tandem
5.
Artigo em Inglês | MEDLINE | ID: mdl-34266625

RESUMO

Deoxynivalenol (DON), zearalenone (ZEN), and fumonisin B1 (FB1), as the main mycotoxins contaminating rice, often coexist in food. Thus, we have measured the genotoxicity of the three rice fungal contaminants, singly and in different combinations, with a 28-day multi-endpoint (Pig-a assay + in vivo micronucleus [MN] test + comet assay) genotoxicity platform. Male Sprague-Dawley rats received the agents orally via gavage for 28 consecutive days, before performing the abovementioned tests. Results indicated that low dose of a single mycotoxin did not show significant genotoxicity. However, some of these mycotoxins in combination induced significant genotoxicity in the peripheral blood and tissues, at sacrifice. In the peripheral blood, the binary combination of DON and FB1 significantly induced MN. In the liver, ZEN might aggravate the DNA-damaging effects of DON and FB1. Therefore, the genotoxicity of sub-chronic exposure to mycotoxins in combination cannot be ignored.


Assuntos
Micotoxinas/toxicidade , Oryza/toxicidade , Animais , Ensaio Cometa/métodos , Dano ao DNA/efeitos dos fármacos , Fumonisinas/toxicidade , Masculino , Ratos , Ratos Sprague-Dawley , Tricotecenos/toxicidade , Zearalenona/toxicidade
6.
Toxicon ; 200: 78-86, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34252445

RESUMO

Fungi in the Fusarium genus produce trichothecene mycotoxins including deoxynivalenol (DON) and T-2 toxin which may elicit their damaging effects on the gastrointestinal tract following the consumption of contaminated cereal-based foods. The aim of our study was to evaluate the effects of these commonly occurring fusarotoxins alone and in combination using the human, non-cancerous intestinal epithelial cell line HIEC-6. Based on our experimental data, 24 h after treatment with fusarotoxins, hydrogen peroxide levels, intracellular oxidative stress and the amounts of inflammatory interleukins IL-6 and IL-8 significantly increased. Cell membrane localization of the tight junction protein claudin-1 decreased, whereas distribution of occludin remained unchanged. Taken together, the HIEC-6 cell line appears to be a suitable experimental model for monitoring the combined effects of mycotoxins at the cellular level including changes in the redox states of cells.


Assuntos
Micotoxinas , Toxina T-2 , Células Epiteliais , Contaminação de Alimentos/análise , Humanos , Micotoxinas/toxicidade , Estresse Oxidativo , Toxina T-2/toxicidade , Tricotecenos
7.
J Agric Food Chem ; 69(28): 7817-7830, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34250809

RESUMO

The genus Alternaria is widely distributed in the environment. Numerous species of the genus Alternaria can produce a variety of toxic secondary metabolites, called Alternaria mycotoxins. In this review, natural occurrence, toxicity, metabolism, and analytical methods are introduced. The contamination of these toxins in foodstuffs is ubiquitous, and most of these metabolites present genotoxic and cytotoxic effects. Moreover, Alternaria toxins are mainly hydroxylated to catechol metabolites and combined with sulfate and glucuronic acid in in vitro arrays. A more detailed summary of the metabolism of Alternaria toxins is presented in this work. To effectively detect and determine the mycotoxins in food, analytical methods with high sensitivity and good accuracy are also reviewed. This review will guide the formulation of maximum residue limit standards in the future, covering both toxicity and metabolic mechanism of Alternaria toxins.


Assuntos
Micotoxinas , Alternaria , Alimentos , Contaminação de Alimentos/análise , Micotoxinas/análise , Micotoxinas/toxicidade
8.
Int J Mol Sci ; 22(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208060

RESUMO

Mycotoxins are toxic metabolites of filamentous fungi. Previous studies demonstrated the co-occurrence of Fusarium and Alternaria toxins, including zearalenone (ZEN), ZEN metabolites, and alternariol (AOH). These xenoestrogenic mycotoxins appear in soy-based meals and dietary supplements, resulting in the co-exposure to ZEN and AOH with the phytoestrogen genistein (GEN). In this study, the cytotoxic and estrogenic effects of ZEN, reduced ZEN metabolites, AOH, and GEN are examined to evaluate their individual and combined impacts. Our results demonstrate that reduced ZEN metabolites, AOH, and GEN can aggravate ZEN-induced toxicity; in addition, the compounds tested exerted mostly synergism or additive combined effects regarding cytotoxicity and/or estrogenicity. Therefore, these observations underline the importance and the considerable risk of mycotoxin co-exposure and the combined effects of mycoestrogens with phytoestrogens.


Assuntos
Estrogênios/toxicidade , Genisteína/toxicidade , Lactonas/toxicidade , Zearalenona/metabolismo , Zearalenona/toxicidade , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Genisteína/química , Células HeLa , Humanos , Lactonas/química , Micotoxinas/toxicidade , Oxirredução , Zearalenona/química
9.
Food Chem Toxicol ; 154: 112308, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34062223

RESUMO

Co-occurrence of emerging and regulated mycotoxins in contaminated samples has been widely documented, but studies about their combined toxicity are scarce. In this report, the regulated mycotoxins deoxynivalenol, fumonisin B1 and zearalenone, and the emerging ones enniatin A, enniatin B and beauvericin were tested in SH-SY5Y human neuroblastoma cells. Their individual and binary combined effects on cell viability and mitochondrial function were evaluated. The results with individual mycotoxins revealed that deoxynivalenol and emerging mycotoxins were the most damaging to neuronal cells, presenting IC50 values between 0.35 and 2.4 µM. Interestingly, non-regulated mycotoxins triggered apoptosis by affecting to mitochondrial membrane potential. However, when regulated and non-regulated mycotoxins were binary mixed, antagonistic effects were found in all cases. Finally, cow feed and milk extracts were analysed by UHPLC-MS/MS, detecting the presence of several mycotoxins included in this study. These extracts were tested in neuroblastoma cells, and damaging effects on cell viability were found. Although binary combinations of mycotoxins produced antagonistic effects, their mixture in natural matrixes induces greater effects than expected. Therefore, it would be interesting to explore the matrix influence on mycotoxin toxicity, and to continue studying the neurotoxic mechanism of action of emerging mycotoxins, as they could be a health hazard.


Assuntos
Mitocôndrias/efeitos dos fármacos , Micotoxinas/toxicidade , Neurônios/efeitos dos fármacos , Ração Animal/análise , Animais , Apoptose/efeitos dos fármacos , Bovinos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Contaminação de Alimentos/análise , Humanos , Leite/química , Micotoxinas/análise , Espectrometria de Massas em Tandem
10.
Biochem Pharmacol ; 188: 114586, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33932472

RESUMO

Mycotoxin contamination is an ongoing and growing issue that can create health risks and even cause death. Unfortunately, there is currently a lack of specific therapy against mycotoxins with few side effects. On the other hand, the strategic expression of CXCL17 in mucosal tissues suggests that it may be involved in immune response when exposed to mycotoxins, but the exact role of CXCL17 remains largely unknown. Using Caco-2 as a cell model of the intestinal epithelial barrier (the first line of defense against mycotoxins), we showed that a strong production of ROS-dependent CXCL17 was triggered by mycotoxins via p38 and JNK pathways. Under the mycotoxins stress, CXCL17 modulated enhanced immuno-protective response with a remission of inflammation and apoptosis through PI3K/AKT/mTOR. Based on our observed feedback of CXCL17 to the mycotoxins, we developed the CXCL17-mimetic peptides in silico (CX1 and CX2) that possessed the safety and the capability to ameliorate mycotoxins-inducible inflammation and apoptosis. In this study, the identification of detoxifying feature of CXCL17 is a prominent addition to the chemokine field, pointing out a new direction for curing the mycotoxins-caused damage.


Assuntos
Materiais Biomiméticos/farmacologia , Quimiocinas CXC/biossíntese , Desenvolvimento de Medicamentos/métodos , Micotoxinas/toxicidade , Fragmentos de Peptídeos/farmacologia , Sequência de Aminoácidos , Materiais Biomiméticos/síntese química , Células CACO-2 , Quimiocinas CXC/síntese química , Quimiocinas CXC/genética , Relação Dose-Resposta a Droga , Humanos , Fragmentos de Peptídeos/síntese química , Fragmentos de Peptídeos/genética , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo
11.
Food Chem Toxicol ; 153: 112251, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33961929

RESUMO

Mycotoxins contaminate all types of food and feed, threatening human and animal health through food chain accumulation, producing various toxic effects. Increasing attention is being focused on the molecular mechanism of mycotoxin-induced toxicity in all kinds of in vivo and in vitro models. Epigenetic alterations, including DNA methylation, non-coding RNAs (ncRNAs), and protein post-translational modifications (PTMs), were identified as being involved in various types of mycotoxin-induced toxicity. In this review, the emphasis was on summarizing the epigenetic alterations induced by mycotoxin, including aflatoxin B1 (AFB1), ochratoxin A (OTA), zearalenone (ZEA), fumonisin B1 (FB1), and deoxynivalenol (DON). This review summarized and analyzed the roles of DNA methylation, ncRNAs, and protein PTMs after mycotoxin exposure based on recently published papers. Moreover, the main research methods and their deficiencies were determined, while some remedial suggestions are proposed. In summary, this review helps to understand better the epigenetic alterations induced by the non-genotoxic effects of mycotoxin.


Assuntos
Epigênese Genética/efeitos dos fármacos , Micotoxinas/toxicidade , Animais , Humanos , Micotoxinas/química
12.
Food Chem Toxicol ; 153: 112261, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34015425

RESUMO

Food and feed are daily exposed to mycotoxin contamination which effects may be counteracted by antioxidants like carotenoids. Some mycotoxins as well as carotenoids penetrate the blood brain barrier (BBB) inducing alterations related to redox balance in the mitochondria. Therefore, the in vitro BBB model ECV304 was subcultured for 7 days and exposed to beauvericine, enniatins, ochratoxin A, zearalenone (100 nM each), individually and combined, and pumpkin extract (500 nM). Reactive oxygen species were measured by fluorescence using the dichlorofluorescein diacetate probe at 0 h, 2 h and 4 h. Intracellular ROS generation reported was condition dependent. RNA extraction was performed and gene expression was analyzed by qPCR after 2 h exposure. The selected genes were related to the Electron Transport Chain (ETC) and mitochondrial activity. Gene expression reported upregulation for exposures including mycotoxins plus pumpkin extract versus individual mycotoxins. Beauvericin and Beauvericin-Enniatins exposure significantly downregulated Complex I and pumpkin addition reverted the effect upregulating Complex I. Complex IV was the most downregulated structure of the ETC. Thioredoxin Interacting Protein was the most upregulated gene. These data confirm that mitochondrial processes in the BBB could be compromised by mycotoxin exposure and damage could be modulated by dietary antioxidants like carotenoids.


Assuntos
Carotenoides/farmacologia , Expressão Gênica/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Micotoxinas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Barreira Hematoencefálica/efeitos dos fármacos , Proteínas de Transporte/metabolismo , Linhagem Celular , Cucurbita/química , Depsipeptídeos/toxicidade , Regulação para Baixo/efeitos dos fármacos , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Genes Mitocondriais/efeitos dos fármacos , Humanos , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteína Desacopladora 2/metabolismo , Regulação para Cima/efeitos dos fármacos
13.
Food Chem Toxicol ; 152: 112164, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33819549

RESUMO

Some epidemiological studies with different levels of evidence have pointed to a higher risk of Parkinson's disease (PD) after exposure to environmental toxicants. A practically unexplored potential etiological factor is a group of naturally-occurring fungal secondary metabolites called mycotoxins. The mycotoxin ochratoxin A (OTA) has been reported to be neurotoxic in mice. To further identify if OTA exposure could have a role in PD pathology, Balb/c mice were orally treated with OTA (0.21, 0.5 mg/kg bw) four weeks and left for six months under normal diet. Effects of OTA on the onset, progression of alpha-synuclein pathology and development of motor deficits were evaluated. Immunohistochemical and biochemical analyses showed that oral subchronic OTA treatment induced loss of striatal dopaminergic innervation and dopaminergic cell dysfunction responsible for motor impairments. Phosphorylated alpha-synuclein levels were increased in gut and brain. LAMP-2A protein was decreased in tissues showing alpha-synuclein pathology. Cell cultures exposed to OTA exhibited decreased LAMP-2A protein, impairment of chaperone-mediated autophagy and decreased alpha-synuclein turnover which was linked to miRNAs deregulation, all reminiscent of PD. These results support the hypothesis that oral exposure to low OTA doses in mice can lead to biochemical and pathological changes reported in PD.


Assuntos
Micotoxinas/toxicidade , Ocratoxinas/toxicidade , Doença de Parkinson/etiologia , Doença de Parkinson/metabolismo , Administração Oral , Animais , Neurônios Dopaminérgicos/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Masculino , Mesencéfalo/efeitos dos fármacos , Mesencéfalo/metabolismo , Mesencéfalo/patologia , Camundongos Endogâmicos BALB C , MicroRNAs/metabolismo , Micotoxinas/administração & dosagem , Ocratoxinas/administração & dosagem , Doença de Parkinson/patologia , Parte Compacta da Substância Negra/efeitos dos fármacos , Parte Compacta da Substância Negra/metabolismo , Parte Compacta da Substância Negra/patologia , Fosforilação/efeitos dos fármacos , Fatores de Tempo , alfa-Sinucleína/química , alfa-Sinucleína/metabolismo
14.
Food Chem Toxicol ; 152: 112182, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33838177

RESUMO

The present review aims to give an overview of the literature of the last decade (2010-2020) concerning the occurrence of the type B trichothecene mycotoxin nivalenol (NIV) and its in vitro toxicity, with the purpose of updating information regarding last researches on this mycotoxin. The most recent studies on the possible methods for preventing Fusarium spp. growth and NIV production are also discussed. Recently, various environmental factors have been shown to influence strongly NIV occurrence. However, Fusarium spp. of the NIV genotype have been found almost worldwide. With regard to NIV cytotoxicity, NIV has been reported to cause a marked decrease in cell proliferation in different mammalian cells. In particular, the recent data suggest that organs containing actively proliferating cells represent the main targets of NIV. Moreover, NIV resulted to cause immunosuppression, gastrointestinal toxicity and genotoxicity. However, sufficient evidence of carcinogenicity in humans is currently lacking, and the International Agency for Research on Cancer (IARC) classifies it as a group 3 carcinogen. Further researches and the discovery of effective treatment strategies to prevent NIV contamination and to counteract its toxicity are urgently required against this common food-borne threat to human health and livestock.


Assuntos
Micotoxinas/toxicidade , Tricotecenos/toxicidade , Animais , Linhagem Celular Tumoral , Contaminação de Alimentos , Fusarium/química , Humanos , Fatores Imunológicos/toxicidade , Mucosa Intestinal/efeitos dos fármacos , Mutagênicos/toxicidade , Testes de Toxicidade
15.
Toxicology ; 456: 152784, 2021 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-33872728

RESUMO

Cell cycle progression and programmed cell death are imposed by pathological stimuli of extrinsic or intrinsic including the exposure to neurotoxins, oxidative stress and DNA damage. All can cause abrupt or delayed cell death, inactivate normal cell survival or cell death networks. Nevertheless, the mechanisms of the neuronal cell death are unresolved. One of the cell deaths triggers which have been wildly studied, correspond to mycotoxins produced by Fusarium species, which have been demonstrated cytotoxicity and neurotoxicity through impairing cell proliferation, gene expression and induction of oxidative stress. The aim of present study was to analyze the cell cycle progression and cell death pathway by flow cytometry in undifferentiated SH-SY5Y neuronal cells exposed to α-zearalenol (α-ZEL), ß-zearalenol (ß-ZEL) and beauvericin (BEA) over 24 h and 48 h individually and combined at the following concentration ranges: from 1.56 to 12.5 µM for α-ZEL and ß-ZEL, from 0.39 to 2.5 µM for BEA, from 1.87 to 25 µM for binary combinations and from 3.43 to 27.5 µM for tertiary combination. Alterations in cell cycle were observed remarkably for ß-ZEL at the highest concentration in all treatments where engaged (ß-ZEL, ß-ZEL + BEA and ß-ZEL + α-ZEL), for both 24 h and 48 h. by activating the cell proliferation in G0/G1 phase (up to 43.6 %) and causing delays or arrests in S and G2/M phases (up to 19.6 %). Tertiary mixtures revealed increases of cell proliferation in subG0 phase by 4-folds versus control. Similarly, for cell death among individual treatments ß-ZEL showed a significant growth in early apoptotic cells population at the highest concentration assayed as well as for all combination treatments where ß-ZEL was involved, in both early apoptotic and apoptotic/necrotic cell death pathways.


Assuntos
Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Depsipeptídeos/toxicidade , Micotoxinas/toxicidade , Zearalenona/toxicidade , Apoptose/fisiologia , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Estrogênios não Esteroides/toxicidade , Humanos
16.
Toxicology ; 456: 152786, 2021 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-33872729

RESUMO

Ustilaginoidins, a group of bis-naphtho-γ-pyrones, are one of the major mycotoxins produced by Ustilaginoidea virens. This group of bis-naphtho-γ-pyrone mycotoxins has been demonstrated to have antibacterial and immunological inhibitory activities and strong cytotoxicity to human oral epidermoid carcinoma. However, little is yet known about the toxicity of ustilaginoidins to animals or toxicity mechanisms. In this study, toxicity assays to zebrafish larvae show that ustilaginoidin D is highly toxic to zebrafish with an LC50 of ∼7.50 µM. Ustilaginoidin D causes an obvious yolk sac absorption delay and liver damage in zebrafish, which is indicated by liver atrophy and the increased alanine and aspartate transaminase activities. Interestingly, different doses of ustilaginoidin D can alter zebrafish movement behavior in a distinct manner. Transcriptome analyses show that global gene expression profiling in zebrafish is significantly changed in response to ustilaginoidin D exposure. KEGG pathway analyses reveal that differentially expressed genes are enriched in the pathways related to lipid metabolism and hyperbilirubinemia, which are indicators of severe liver injury. Consistently, the expression of the marker genes for hepatotoxic responses is significantly induced by ustilaginoidin D. The findings indicate that ustilaginoidin D induces lipid metabolism disorders and hepatotoxicity in zebrafish larvae and poses a potential risk to food safety.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Hypocreales , Larva/efeitos dos fármacos , Larva/metabolismo , Locomoção/efeitos dos fármacos , Micotoxinas/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/patologia , Relação Dose-Resposta a Droga , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/fisiologia , Locomoção/fisiologia , Micotoxinas/isolamento & purificação , Peixe-Zebra
17.
Toxins (Basel) ; 13(4)2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33917534

RESUMO

Fungal phytotoxic secondary metabolites are poisonous substances to plants produced by fungi through naturally occurring biochemical reactions. These metabolites exhibit a high level of diversity in their properties, such as structures, phytotoxic activities, and modes of toxicity. They are mainly isolated from phytopathogenic fungal species in the genera of Alternaria, Botrytis, Colletotrichum, Fusarium, Helminthosporium, and Phoma. Phytotoxins are either host specific or non-host specific phytotoxins. Up to now, at least 545 fungal phytotoxic secondary metabolites, including 207 polyketides, 46 phenols and phenolic acids, 135 terpenoids, 146 nitrogen-containing metabolites, and 11 others, have been reported. Among them, aromatic polyketides and sesquiterpenoids are the main phytotoxic compounds. This review summarizes their chemical structures, sources, and phytotoxic activities. We also discuss their phytotoxic mechanisms and structure-activity relationships to lay the foundation for the future development and application of these promising metabolites as herbicides.


Assuntos
Fungos/metabolismo , Herbicidas/toxicidade , Micotoxinas/toxicidade , Plantas/efeitos dos fármacos , Animais , Herbicidas/química , Herbicidas/metabolismo , Humanos , Estrutura Molecular , Micotoxinas/química , Micotoxinas/metabolismo , Metabolismo Secundário , Relação Estrutura-Atividade
18.
Toxins (Basel) ; 13(3)2021 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799633

RESUMO

Maize silage, which in Europe is the main feed for dairy cattle in winter, can be contaminated by mycotoxins. Mycotoxigenic Fusarium spp. originating from field infections may survive in badly sealed silages or re-infect at the cutting edge during feed-out. In this way, mycotoxins produced in the field may persist during the silage process. In addition, typical silage fungi such as Penicillium spp. and Aspergillus spp. survive in silage conditions and produce mycotoxins. In this research, 56 maize silages in Flanders were sampled over the course of three years (2016-2018). The concentration of 22 different mycotoxins was investigated using a multi-mycotoxin liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and the presence of DNA of three Fusarium spp. (F. graminearum, F. culmorum and F. verticillioides) was analyzed in a selection of these samples using quantitative polymerase chain reaction (qPCR). Every maize silage contained at least two different mycotoxins. Nivalenol (NIV) and deoxynivalenol (DON) were the most prevalent (both in 97.7% of maize silages), followed by ENN B (88.7%). Concentrations often exceeded the EU recommendations for DON and zearalenone (ZEN), especially in 2017 (21.3% and 27.7% of the maize silages, respectively). No correlations were found between fungal DNA and mycotoxin concentrations. Furthermore, by ensiling maize with a known mycotoxin load in a net bag, the mycotoxin contamination could be monitored from seed to feed. Analysis of these net bag samples revealed that the average concentration of all detected mycotoxins decreased after fermentation. We hypothesize that mycotoxins are eluted, degraded, or adsorbed during fermentation, but certain badly preserved silages are prone to additional mycotoxin production during the stable phase due to oxygen ingression, leading to extremely high toxin levels.


Assuntos
Ração Animal/microbiologia , Microbiologia de Alimentos , Armazenamento de Alimentos , Fungos/metabolismo , Micotoxinas/análise , Sementes/microbiologia , Zea mays/microbiologia , Criação de Animais Domésticos , Animais , Bélgica , Cromatografia Líquida , Indústria de Laticínios , Fungos/genética , Micotoxinas/toxicidade , Reação em Cadeia da Polimerase , Espectrometria de Massas em Tandem , Fatores de Tempo
19.
Toxins (Basel) ; 13(3)2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33801997

RESUMO

Seeking useful biological agents for mycotoxin detoxification has achieved success in the last twenty years thanks to the participation of many multidisciplinary teams. We have recently witnessed discoveries in the fields of bacterial genetics (inclusive of next-generation sequencing), protein encoding, and bioinformatics that have helped to shape the latest perception of how microorganisms/mycotoxins/environmental factors intertwine and interact, so the road is opened for new breakthroughs. Analysis of literature data related to the biological control of mycotoxins indicates the ability of yeast, bacteria, fungi and enzymes to degrade or adsorb mycotoxins, which increases the safety and quality of susceptible crops, animal feed and, ultimately, food of animal origin (milk, meat and eggs) by preventing the presence of residues. Microbial detoxification (transformation and adsorption) is becoming a trustworthy strategy that leaves no or less toxic compounds and contributes to food security. This review summarizes the data and highlights the importance and prospects of these methods.


Assuntos
Ração Animal/microbiologia , Proteção de Cultivos , Produtos Agrícolas/microbiologia , Contaminação de Alimentos/prevenção & controle , Fungos/metabolismo , Micotoxinas/metabolismo , Controle Biológico de Vetores , Adsorção , Animais , Produtos Agrícolas/genética , Produtos Agrícolas/crescimento & desenvolvimento , Abastecimento de Alimentos , Humanos , Inativação Metabólica , Micotoxinas/toxicidade , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/microbiologia
20.
J Toxicol Sci ; 46(4): 157-165, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33814509

RESUMO

Enniatins are so-called "emerging mycotoxins" that commonly occur in milligrams per kilogram levels in grains and their derived products, as well as in fish, dried fruits, nuts, spices, cocoa, and coffee. The present study investigated the 28-day repeated oral dose toxicity of enniatin complex in CD1(ICR) mice. Enniatin B, enniatin B1, and enniatin A1 at a ratio of 4:4:1 were administered to male and female mice at doses of 0 (vehicle controls), 0.8, 4, and 20 mg/kg body weight/day. In life parameters did not change during the study period, with the exception of slight reductions in food consumption in male mice administered 4 and 20 mg/kg and in female mice administered 20 mg/kg. Body and organ weights did not change, and no alterations in hematology, blood biochemistry, or histopathology parameters were observed at the end of the administration period. Thus, we determined that the no-observed-adverse-effect level of enniatin complex was 20 mg/kg/day for both sexes under the present experimental conditions.


Assuntos
Depsipeptídeos/administração & dosagem , Depsipeptídeos/toxicidade , Micotoxinas/administração & dosagem , Micotoxinas/toxicidade , Administração Oral , Animais , Análise Química do Sangue , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Masculino , Camundongos Endogâmicos ICR , Nível de Efeito Adverso não Observado , Tamanho do Órgão , Fatores de Tempo
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