RESUMO
This study investigated the immunotoxic effects of the mycotoxin nivalenol (NIV) using antigen-presenting cells and a mouse model of atopic dermatitis (AD). In vitro experiments were conducted using a mouse macrophage cell line (RAW 264.7) and mouse dendritic cell line (DC 2.4). After cells were exposed to NIV (0.19-5 µmol) for 24 h, the production of pro-inflammatory cytokines (IL-1ß, IL-6, and TNFα) was quantified. To further investigate the inflammatory cytokine production pathway, the possible involvement of mitogen-activated protein kinase (MAPK) pathways, such as ERK1/2, p-38, and JNK, in NIV exposure was analyzed using MAPK inhibitors and phosphorylation analyses. In addition, the pro-inflammatory effects of oral exposure to NIV at low concentrations (1 or 5 ppm) were evaluated in an NC/Nga mouse model of hapten-induced AD. In vitro experiments demonstrated that exposure to NIV significantly enhanced the production of TNFα. In addition, it also directly induced the phosphorylation of MAPK, indicated by the inhibition of TNFα production following pretreatment with MAPK inhibitors. Oral exposure to NIV significantly exacerbated the symptoms of AD, including a significant increase in helper T cells and IgE-produced B cells in auricular lymph nodes and secretion of pro-inflammatory cytokines, such as IL-4, IL-5, and IL-13, compared with the vehicle control group. Our findings indicate that exposure to NIV directly enhanced the phosphorylation of ERK1/2, p-38, and JNK, resulting in a significant increase in TNFα production in antigen-presenting cells, which is closely related to the development of atopic dermatitis.
Assuntos
Citocinas , Dermatite Atópica , Tricotecenos , Animais , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/imunologia , Tricotecenos/toxicidade , Tricotecenos/administração & dosagem , Camundongos , Administração Oral , Citocinas/metabolismo , Células RAW 264.7 , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Células Apresentadoras de Antígenos/efeitos dos fármacos , Células Apresentadoras de Antígenos/imunologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Modelos Animais de Doenças , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Células Dendríticas/imunologia , Fosforilação , Masculino , Fator de Necrose Tumoral alfa/metabolismo , FemininoRESUMO
Oocyte maturation is essential for fertilization and early embryo development, and proper organelle functions guarantee this process to maintain high-quality oocytes. The type B trichothecene nivalenol (NIV) is a mycotoxin produced by Fusarium oxysporum and is commonly found in contaminated food. NIV intake affect growth, the immune system, and the female reproductive system. Here, we investigated NIV toxicity on mouse oocyte quality. Transcriptome analysis results showed that NIV exposure altered the expression of multiple genes involved in spindle formation and organelle function in mouse oocytes, indicating its toxicity on mouse oocyte maturation. Further analysis indicated that NIV exposure disrupted spindle structure and chromosome alignment, possibly through tubulin acetylation. NIV exposure induced aberrant mitochondria distribution and reduced mitochondria number, mitochondria membrane potential (MMP), and ATP levels. In addition, NIV caused the abnormal distribution of the Golgi apparatus and altered the expression of the vesicle trafficking protein Rab11. ER distribution was also disturbed under NIV exposure, indicating the effects of NIV on protein modification and transport in oocytes. Thus, our results demonstrated that NIV exposure affected spindle structure and organelles function in mouse oocytes.
Assuntos
Desenvolvimento Embrionário/efeitos dos fármacos , Oócitos/efeitos dos fármacos , Organelas/efeitos dos fármacos , Fuso Acromático/efeitos dos fármacos , Tricotecenos/efeitos adversos , Acetilação/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Cromossomos/efeitos dos fármacos , Feminino , Meiose/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Micotoxinas/efeitos adversos , Oócitos/metabolismo , Oogênese/efeitos dos fármacos , Organelas/metabolismo , Fuso Acromático/metabolismo , Transcriptoma/efeitos dos fármacos , Tubulina (Proteína)/metabolismoRESUMO
AIMS: Cereals contaminated with type B trichothecene nivalenol (NIV) and its acetylated derivative 4-acetyl-nivalenol (4-AcNIV) are a global mycotoxicological problem threatening the health of humans and livestock. Toxicological studies, quantitative determinations and screening for biodegrading micro-organisms require massive amounts of pure toxins. However, the low yield from fungal cultures and high prices of NIV and 4-AcNIV limit research progress in these areas. This work aimed to select Fusarium asiaticum mutant strains with enhanced production of NIV and 4-AcNIV. METHODS AND RESULTS: A total of 62 NIV-producing F. asiaticum strains were isolated and compared regarding their ability to produce NIV. Strain RR108 had the highest yield of NIV among 62 field isolates surveyed and was then genetically modified for higher production. Targeted deletion of the FaFlbA gene, encoding a regulator of G protein signalling protein, resulted in a significant increase in NIV and 4-AcNIV production in the FaFlbA deletion mutant ΔFaFlbA. The expression of three TRI genes involved in the trichothecene biosynthetic pathway was upregulated in ΔFaFlbA. ΔFaFlbA produced the highest amount of NIV and 4-AcNIV when cultured in brown long-grain rice for 21 days, and the yields were 2.07 and 2.84 g kg-1 , respectively. The mutant showed reduced fitness, including reduced conidiation, loss of perithecial development and decreased virulence on wheat heads, which makes it biologically safe for large-scale preparation and purification of NIV and 4-AcNIV. CONCLUSIONS: The F. asiaticum mutant strain ΔFaFlbA presented improved production of NIV and 4-AcNIV with reduced fitness and virulence in plants. SIGNIFICANCE AND IMPACT OF THE STUDY: Targeted deletion of the FaFlbA gene resulted in increased NIV and 4-AcNIV production. Our results provide a practical approach using genetic modification for large-scale mycotoxin production.
Assuntos
Fusarium , Tricotecenos , Fusarium/genética , Fusarium/metabolismo , Humanos , Tricotecenos/metabolismo , Triticum/microbiologiaRESUMO
Mycotoxins, toxic secondary metabolites produced by fungi, are important contaminants in food and agricultural industries around the world. These toxins have a multidirectional toxic effect on living organisms, causing damage to the kidneys and liver, and disrupting the functions of the digestive tract and the immune system. In recent years, much attention has been paid to the biological control of pathogens and the mycotoxins they produce. In this study, selected yeasts were used to reduce the occurrence of deoxynivalenol (DON), nivalenol (NIV), and zearalenone (ZEA) produced by Fusarium culmorum, F. graminearum, and F. poae on wheat grain and bread. In a laboratory experiment, an effective reduction in the content of DON, NIV, and ZEA was observed in bread prepared by baking with the addition of an inoculum of the test yeast, ranging from 16.4% to 33.4%, 18.5% to 36.2% and 14.3% to 35.4%, respectively. These results indicate that the selected yeast isolates can be used in practice as efficient mycotoxin decontamination agents in the food industry.
Assuntos
TricotecenosRESUMO
BACKGROUND: Fusarium poae is one of the most common Fusarium head blight (FHB) causal agents in wheat. This species can biosynthesize a wide range of mycotoxins, in particular nivalenol (NIV). In FHB epidemiology, infection timing is important for disease occurrence, kernel development, symptom appearance and mycotoxin accumulation in grain. The present study explored, both in a controlled environment and in a 2-year field plot experiment in Central Italy, the influence of five infection timings (from beginning of flowering to medium milk growth stage) on F. poae colonization and mycotoxin accumulation in bread wheat spikes (spring cv. A416 and winter cv. Ambrogio). RESULTS: Both climate chamber and field experiments showed that early infection timings (from beginning of flowering to full flowering) especially favoured F. poae colonization and accumulation of its mycotoxins (particularly NIV) in grain. By contrast, later infection timings (watery ripe and medium milk) reduced F. poae development and mycotoxin levels. The time window of host susceptibility in the field was shorter than that observed under controlled conditions. Symptom expression in kernels also differed among infection timings. In general, F. poae biomass was higher in the chaff than in the grain. CONCLUSION: These results enhance knowledge of a common member of the FHB complex worldwide, and could be useful in forecasting the risk of F. poae infection and mycotoxin contamination. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Assuntos
Fusarium , Micotoxinas , Pão , Grão Comestível/química , Micotoxinas/análise , Doenças das Plantas , Tricotecenos , Triticum/metabolismoRESUMO
Mammalian oocyte quality is critical for fertilization and early embryo development. The type B trichothecene nivalenol (NIV) is a mycotoxin produced by Fusarium oxysporum, and it is commonly found with deoxynivalenol in contaminated food or feed. NIV has been shown to affect the immune system and female reproductive system, cause emesis and growth retardation. Here, we investigated the toxicity of NIV on mouse oocyte quality, as well as the protective effects of melatonin on the NIV-exposed oocytes. We found NIV exposure caused meiotic arrest and further induced the failure of polar body extrusion in mouse oocytes. Transcriptome analysis data showed that NIV exposure altered the expression of multiple pathway-related genes in oocytes, indicating its wide toxicity on oocyte maturation. Based on the RNA-seq data, we showed that NIV exposure induced oxidative stress and caused DNA damage in oocytes. Besides, autophagy, and early apoptosis were also found in NIV-exposed oocytes. Treatment with melatonin significantly ameliorated these defects through its effects on ROS level. Thus, our results demonstrated that exposure to NIV affected oocyte quality and melatonin treatment could reduce the defects caused by NIV in mouse oocytes.
Assuntos
Apoptose , Dano ao DNA , Melatonina/farmacologia , Micotoxinas/toxicidade , Oócitos/efeitos dos fármacos , Estresse Oxidativo , Substâncias Protetoras/farmacologia , Tricotecenos/toxicidade , Animais , Camundongos , Oócitos/fisiologiaRESUMO
In Brazil, Gibberella ear rot (GER) of maize is caused mainly by Fusarium meridionale, whereas F. graminearum is a minor contributor. To test the hypothesis that F. meridionale is more aggressive than F. graminearum on maize, six experiments were conducted in the south (summer) and one in the central-south (winter), totaling seven conditions (year × location × hybrid). Treatments consisted of F. graminearum or F. meridionale (two isolates of each) inoculated once 4 days after silk, inoculated sequentially and alternately (F. graminearum â F. meridionale or F. meridionale â F. graminearum) 6 days apart, or (in the central-south) inoculated sequentially without alternating species (F. meridionale â F. meridionale or F. graminearum â F. graminearum). Overall, severity was two times greater in the south (37.0%), where summer temperatures were warmer (20 to 25°C) than in central-south. In the south, severity was greatest in F. meridionale treatments (67.8%); followed by F. meridionale â F. graminearum (41.1%), then F. graminearum â F. meridionale (19.4%), and lowest in F. graminearum (2.1%), suggesting an antagonistic relationship. In the central-south (15 to 20°C), severity was generally higher in the sequential nonalternating inoculation treatments (F. meridionale â F. meridionale or F. graminearum â F. graminearum) than when either species was inoculated only once. Only nivalenol (NIV) or deoxynivalenol was detected when F. meridionale or F. graminearum, respectively, was inoculated singly, or sequentially with no alternation. Both toxins were found in grains harvested from the F. meridionale â F. graminearum treatment, whereas only NIV was found in kernels from the F. graminearum â F. meridionale treatment, suggesting that F. meridionale was more competitive than F. graminearum in coinoculations. The dominance of F. meridionale as a cause of GER in Brazil may be due in part to its higher aggressiveness and competitiveness compared with F. graminearum.
Assuntos
Fusarium , Gibberella , Brasil , Doenças das PlantasRESUMO
Fusarium culmorum is a worldwide, soil-borne plant pathogen. It causes diseases of cereals, reduces their yield, and fills the grain with toxins. The main direction of modern breeding is to select wheat genotypes the most resistant to Fusarium diseases. This study uses seedlings and plants at the anthesis stage to analyze total soluble carbohydrates, total and cell-wall bound phenolics, chlorophyll content, antioxidant activity, hydrogen peroxide content, mycotoxin accumulation, visual symptoms of the disease, and Fusarium head blight index (FHBi). These results determine the resistance of three durum wheat accessions. We identify physiological or biochemical markers of durum wheat resistance to F. culmorum. Our results confirm correlations between FHBi and mycotoxin accumulation in the grain, which results in grain yield decrease. The degree of spike infection (FHBi) may indicate accumulation mainly of deoxynivalenol and nivalenol in the grain. High catalase activity in the infected leaves could be considered a biochemical marker of durum sensitivity to this fungus. These findings allowed us to formulate a strategy for rapid evaluation of the disease severity and the selection of plants with higher level, or resistance to F. culmorum infection.
Assuntos
Biomarcadores/metabolismo , Fusarium/fisiologia , Doenças das Plantas/microbiologia , Plântula/fisiologia , Tricotecenos/metabolismo , Triticum/fisiologia , Genótipo , Plântula/microbiologia , Triticum/classificação , Triticum/genética , Triticum/microbiologiaRESUMO
Surveys for crown rot (FCR) and head blight (FHB) of Algerian wheat conducted during 2014 and 2015 revealed that Fusarium culmorum strains producing 3-acetyl-deoxynivalenol (3ADON) or nivalenol (NIV) were the causal agents of these important diseases. Morphological identification of the isolates (n FCR=110, n FHB=30) was confirmed by sequencing a portion of TEF1. To assess mating type idiomorph, trichothecene chemotype potential and global population structure, the Algerian strains were compared with preliminary sample of F. culmorum from Italy (n=27), Australia (n=30) and the United States (n=28). A PCR assay for MAT idiomorph revealed that MAT1-1 and MAT1-2 strains were segregating in nearly equal proportions, except within Algeria where two-thirds of the strains were MAT1-2. An allele-specific PCR assay indicated that the 3ADON trichothecene genotype was predominant globally (83.8% 3ADON) and in each of the four countries sampled. In vitro toxin analyses confirmed trichothecene genotype PCR data and demonstrated that most of the strains tested (77%) produced culmorin. Global population genetic structure of 191 strains was assessed using nine microsatellite markers (SSRs). AMOVA of the clone corrected data indicated that 89% of the variation was within populations. Bayesian analysis of the SSR data identified two globally distributed, sympatric populations within which both trichothecene chemotypes and mating types were represented.
Assuntos
Fusarium/genética , Genética Populacional , Micotoxinas/genética , Argélia , Fusarium/patogenicidade , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Triticum/microbiologiaRESUMO
Fusarium Head Blight is a disease of cereal crops that causes severe yield losses and mycotoxin contamination of grain. The main causal pathogen, Fusarium graminearum, produces the trichothecene toxins deoxynivalenol or nivalenol as virulence factors. Nivalenol-producing isolates are most prevalent in Asia but co-exist with deoxynivalenol producers in lower frequency in North America and Europe. Previous studies identified a barley UDP-glucosyltransferase, HvUGT13248, that efficiently detoxifies deoxynivalenol, and when expressed in transgenic wheat results in high levels of type II resistance against deoxynivalenol-producing F. graminearum. Here we show that HvUGT13248 is also capable of converting nivalenol into the non-toxic nivalenol-3-O-ß-d-glucoside. We describe the enzymatic preparation of a nivalenol-glucoside standard and its use in development of an analytical method to detect the nivalenol-glucoside conjugate. Recombinant Escherichia coli expressing HvUGT13248 glycosylates nivalenol more efficiently than deoxynivalenol. Overexpression in yeast, Arabidopsis thaliana, and wheat leads to increased nivalenol resistance. Increased ability to convert nivalenol to nivalenol-glucoside was observed in transgenic wheat, which also exhibits type II resistance to a nivalenol-producing F. graminearum strain. Our results demonstrate the HvUGT13248 can act to detoxify deoxynivalenol and nivalenol and provide resistance to deoxynivalenol- and nivalenol-producing Fusarium.
Assuntos
Fusarium/metabolismo , Glucosiltransferases/genética , Hordeum/genética , Doenças das Plantas/genética , Proteínas de Plantas/genética , Tricotecenos/metabolismo , Resistência à Doença/genética , Glucosiltransferases/metabolismo , Hordeum/enzimologia , Hordeum/microbiologia , Interações Hospedeiro-Patógeno , Doenças das Plantas/microbiologia , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Plantas Geneticamente Modificadas/microbiologia , Triticum/genética , Triticum/metabolismo , Triticum/microbiologiaRESUMO
Durum wheat (Triticum turgidum var. durum) is an important crop in Europe, particularly in the Mediterranean countries. Fusarium head blight (FHB) is considered as one of the most damaging diseases, resulting in yield and quality reduction as well as contamination of grain with mycotoxins. Three winter durum wheat cultivars originating from Austria, Slovakia, and Poland were analyzed during 2012-2014 seasons for FHB incidence and Fusarium mycotoxin accumulation in harvested grain. Moreover, the effects of sowing density and delayed sowing date were evaluated in the climatic conditions of Southern Poland. Low disease severity was observed in 2011/2012 in all durum wheat cultivars analyzed, and high FHB occurrence was recorded in 2012/2013 and 2013/2014 seasons. Fusarium graminearum was the most abundant pathogen, followed by Fusarium avenaceum. Through all three seasons, cultivar Komnata was the most susceptible to FHB and to mycotoxin accumulation, while cultivars Auradur and IS Pentadur showed less symptoms. High susceptibility of cv. Komnata was reflected by the number of Fusarium isolates and elevated mycotoxin (deoxynivalenol, zearalenone, and moniliformin) content in the grain of this cultivar across all three seasons. Nivalenol was identified in the samples of cv. Komnata only. Genotype-dependent differences in FHB susceptibility were observed for the plants sown at optimal date but not at delayed sowing date. It can be hypothesized that cultivars bred in Austria and Slovakia show less susceptibility towards FHB than the cultivar from Poland because of the environmental conditions allowing for more efficient selection of breeding materials.
Assuntos
Fusarium/fisiologia , Micotoxinas/análise , Triticum/química , Região do Mediterrâneo , Micotoxinas/metabolismo , Especificidade da Espécie , Fatores de Tempo , Triticum/metabolismoRESUMO
The global incidence of Fusarium head blight and attendant cereal grains multi-contamination by the trichothecene mycotoxins deoxynivalenol (DON) and nivalenol (NIV) are increasing as a possible result of climate change and inadequate agricultural practices. At the molecular level, these mycotoxins bind to the ribosome, activate the mitogen-activated protein kinase and induce a local and systemic inflammation. DON is of public health concern owing to the narrow margin between exposure and tolerable daily intake. The intestinal inflammatory response to DON, NIV and their mixture was analyzed to determine thresholds for their intestinal pro-inflammatory effects and characterize the type and magnitude of their interaction. Fully differentiated three-dimensional porcine jejunal explants were exposed to increasing doses of DON and NIV alone or in combination; the expression levels of IL-1α, IL-1ß, IL-8, IL-17A and IL-22 were measured by RT-PCR. Doses as low as 0.16 µM DON or 0.73 µM NIV significantly increase the intestinal expression levels of the tested inflammation-related genes. These doses are lower than those previously reported for other intestinal toxicity endpoints. The combined pro-inflammatory activity of DON and NIV was synergistic for all the tested genes with combination index value range of 0.23-0.8. Our results indicate that (1) inflammation is a very sensitive endpoint for the intestinal toxicity of the trichothecenes and (2) co-exposure to DON and NIV has a greater inflammatory effect than induced by mycotoxins alone. This synergy should be taken into account considering the frequent co-occurrence of DON and NIV in the diet.
Assuntos
Contaminação de Alimentos , Jejuno/efeitos dos fármacos , Tricotecenos/toxicidade , Animais , Citocinas/genética , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Enterite/induzido quimicamente , Enterite/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Doenças do Jejuno/induzido quimicamente , Doenças do Jejuno/patologia , Jejuno/patologia , Micotoxinas/administração & dosagem , Micotoxinas/toxicidade , Técnicas de Cultura de Órgãos/métodos , Suínos , Testes de Toxicidade/métodos , Tricotecenos/administração & dosagemRESUMO
Mycotoxins are secondary fungal metabolites often found as contaminants in almost all agricultural commodities worldwide, and the consumption of food or feed contaminated by mycotoxins represents a major risk for human and animal health. Reactive oxygen species are normal products of cellular metabolism. However, disproportionate generation of reactive oxygen species poses a serious problem to bodily homeostasis and causes oxidative tissue damage. In this study we analyzed the effect of two trichothecenes mycotoxins: nivalenol and deoxynivalenol, alone and in combination, on oxidative stress in the non-tumorigenic intestinal epithelial cell line IEC-6. Our results indicate the pro-oxidant nivalenol effect in IEC-6, the stronger pro-oxidant effect of nivalenol when compared to deoxynivalenol and, interestingly, that nivalenol increases deoxynivalenol pro-oxidative effects. Mechanistic studies indicate that the observed effects were mediated by NADPH oxidase, calcium homeostasis alteration, NF-kB and Nrf2 pathways activation and by iNOS and nitrotyrosine formation. The toxicological interaction by nivalenol and deoxynivalenol reported in this study in IEC-6, points out the importance of the toxic effect of these mycotoxins, mostly in combination, further highlighting the risk assessment process of these toxins that are of growing concern.
Assuntos
Células Epiteliais/metabolismo , Mucosa Intestinal/metabolismo , Micotoxinas/toxicidade , Oxidantes/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Tricotecenos/toxicidade , Animais , Sinalização do Cálcio/efeitos dos fármacos , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Intestinos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMO
BACKGROUND: Fusarium head blight (FHB) of wheat is an important disease causing yield losses and mycotoxin contamination. The aim of the work was to detect and characterise trichothecene producing Fusarium species in durum and soft wheat cultivated in an area of central Italy in 2009 and 2010 and to determine trichothecene contamination by LC-MS/MS in the grain. RESULTS: F. graminearum s. str. was the most frequent species. In 2009, the occurrence of F. avenaceum and F. poae was higher than in 2010. Among F. graminearum strains, the 15-acetyl deoxynivalenol (15-ADON) chemotype could be found more frequently, followed by nivalenol (NIV) and 3-ADON chemotypes, while all F. culmorum isolates belonged to the 3-ADON chemotype. All F. poae strains were NIV chemotypes. In vitro trichothecene production confirmed molecular characterisation. Durum wheat was characterised by a higher average DON contamination with respect to soft wheat, NIV was always detected at appreciable levels while type-A trichothecenes were mostly found in durum wheat samples in 2009 with 6% of samples exceeding the contamination level recently recommended by the European Union. CONCLUSION: Climatic conditions were confirmed to be predominant factors influencing mycotoxigenic species composition and mycotoxin contaminations. However, NIV contamination was found to occur irrespective of climatic conditions, suggesting that it may often represent an under-estimated risk to be further investigated.
Assuntos
DNA Fúngico/análise , Contaminação de Alimentos/análise , Fusarium/genética , Tricotecenos/análise , Triticum/microbiologia , Cromatografia Líquida , Microbiologia de Alimentos , Fusarium/química , Genótipo , Humanos , Itália , Doenças das Plantas/microbiologia , Reação em Cadeia da Polimerase , Sementes/química , Sementes/microbiologia , Especificidade da Espécie , Espectrometria de Massas em Tandem , Triticum/químicaRESUMO
Nivalenol (NIV) is a trichothecene mycotoxin produced by Fusarium fungi that frequently contaminates agricultural commodities. Dietary administration of NIV to adult mice affects the renal glomeruli, but data about NIV toxicity in human infants are limited. To evaluate the effects of NIV on infant kidneys, 3-week-old male ICR-derived glomerulonephritis (ICGN) and ICR mice were administered 0, 4, 8 or 16 ppm NIV in diet for 4 weeks, and their renal status was compared with age-matched or adult ICR mice. In ICGN mice, the number of glomeruli showing mesangial expansion and α-smooth muscle actin (SMA)-positive mesangial cells was higher with 16 ppm NIV compared with controls. No other significant differences were observed in ICGN mice. In infant ICR mice, the IgA serum concentrations were significantly elevated without glomerular morphological changes in the 16 ppm NIV group. There was no difference in NIV sensitivity in the kidneys of infant ICGN and ICR mice. These data suggest that the kidneys in infant mice are not sensitive to nivalenol under the present conditions.
RESUMO
This study reports levels of mycotoxins in sorghum from Niger State, Nigeria, and provides a comprehensive assessment of their potential health risks by combining mycotoxin levels and dietary exposure assessment. A total of 240 samples of red and white sorghum were collected from both stores and markets across four microclimatic zones. Fungal species were identified using a dilution plate method. Aflatoxins (AFs), deoxynivalenol, nivalenol, and ochratoxin (OTA) were quantified using HPLC, whereas cyclopiazonic acid, fumonisins (FUMs) and zearalenone were quantified using ELISA. A. flavus and A. fumigatus were dominant fungal species followed by F. verticilloides, A. oryzae and P. verrucosum. Aflatoxins (mean: 29.97 µg/kg) were detected in all samples, whereas OTA (mean: 37.5 µg/kg) and FUMs (mean: 3269.8 µg/kg) were detected in 72% and 50% of the samples, respectively. Mycotoxins frequently co-occurred in binary mixtures of AFs + OTA and AFs + FUMs. Dietary exposure estimates were highest for FUMs at 230% of TDI and margin of exposures (MOEs) for both AFs and OTA (<10,000) indicating a potential risk associated with combined exposure to AFs and OTA. The Risk of hepatocellular carcinoma cases (HCC/year) attributable to AFs and OTA exposure from sorghum was estimated to be 5.99 × 105 and 0.24 × 105 cases for HBsAg + individuals based on 13.6% HBV incidence. Similarly, the HCC/year for AFs and OTA were assessed to be 3.59 × 105 and 0.14 × 105 at an 8.1% prevalence rate. Therefore, the results of this study demonstrate the high prevalence and dietary exposure to mycotoxins through sorghum consumption, raising public health and trade concerns.
Assuntos
Aflatoxinas , Carcinoma Hepatocelular , Fumonisinas , Neoplasias Hepáticas , Micotoxinas , Sorghum , Humanos , Micotoxinas/análise , Exposição Dietética/análise , Nigéria , Níger , Contaminação de Alimentos/análise , Aflatoxinas/análise , Fumonisinas/análise , Grão Comestível/químicaRESUMO
Deoxynivalenol (DON) is the most prevalent trichothecene mycotoxin in crops in Europe and North America. DON is often present with other type B trichothecenes such as 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), nivalenol (NIV) and fusarenon-X (FX). Although the cytotoxicity of individual mycotoxins has been widely studied, data on the toxicity of mycotoxin mixtures are limited. The aim of this study was to assess interactions caused by co-exposure to Type B trichothecenes on intestinal epithelial cells. Proliferating Caco-2 cells were exposed to increasing doses of Type B trichothecenes, alone or in binary or ternary mixtures. The MTT test and neutral red uptake, respectively linked to mitochondrial and lysosomal functions, were used to measure intestinal epithelial cytotoxicity. The five tested mycotoxins had a dose-dependent effect on proliferating enterocytes and could be classified in increasing order of toxicity: 3-ADON<15-ADON≈DONAssuntos
Células Epiteliais/efeitos dos fármacos
, Mucosa Intestinal/citologia
, Mucosa Intestinal/efeitos dos fármacos
, Micotoxinas/toxicidade
, Tricotecenos/toxicidade
, Algoritmos
, Células CACO-2
, Sobrevivência Celular/efeitos dos fármacos
, Corantes
, Relação Dose-Resposta a Droga
, Sinergismo Farmacológico
, Humanos
, Sais de Tetrazólio
, Tiazóis
RESUMO
Fusarium graminearum (FG) and Fusarium verticillioides (FV) co-occur in infected plants and plant residues. In maize ears, the growth of FV is stimulated while FG is suppressed. To elucidate the role of mycotoxins in these effects, we used FG mutants with disrupted synthesis of nivalenol (NIV) and deoxynivalenol (DON) and a FV mutant with disrupted synthesis of fumonisins to monitor fungal growth in mixed cultures in vitro and in co-infected plants by real-time PCR. In autoclaved grains as well as in maize ears, the growth of FV was stimulated by FG regardless of the production of DON or NIV by the latter, whereas the growth of FG was suppressed. In autoclaved grains, fumonisin-producing FV suppressed FG more strongly than a fumonisin-nonproducing strain, indicating that fumonisins act as interference competition agents. In co-infected maize ears, FG suppression was independent of fumonisin production by FV, likely due to heterogeneous infection and a lower level of fumonisins in planta. We conclude that (i) fumonisins are agents of interference competition of FV, and (ii) trichothecenes play no role in the interaction between FG and FV. We hypothesize the following: (i) In vitro, FG stimulates the FV growth by secreting hydrolases that mobilize nutrients. In planta, suppression of plant defense by FG may additionally play a role. (ii) The biological function of fumonisin production in planta is to protect kernels shed on the ground by accumulating protective metabolites before competitors become established. Therefore, to decipher the biological function of mycotoxins, the entire life history of mycotoxin producers must be considered.
Assuntos
Fumonisinas , Micotoxinas , Zea maysRESUMO
Oocyte maturation is important for fertility in mammals, since the quality of oocytes directly affects fertilization, embryo attachment and survival. Nivalenol is widely present in nature as a common toxin that contaminates grain and feed, and it has been reported to cause acute toxicity, immunotoxicity, reproductive toxicity and carcinogenic effects. In this study, we explored the impact of nivalenol on the porcine oocyte maturation and its possible mechanisms. The extrusion of the first polar body was significantly inhibited after incubating oocytes with nivalenol. Meanwhile, nivalenol exposure led to the abnormal distribution of mitochondria, aberrant calcium concentration and the reduction of membrane potential caused a significant decrease in the capacity of mitochondria to generate ATP. In addition, nivalenol induced oxidative stress, and the level of ROS was significantly increased in the nivalenol-treated group, which was confirmed by the perturbation of oxidative stress-related genes. We found that nivalenol-treated oocytes showed positive Annexin-V and γH2A.X signals, indicating the occurrence of apoptosis and DNA damage. In all, our data suggest that nivalenol disrupted porcine oocyte maturation through its effects on mitochondria-related oxidative stress, apoptosis and DNA damage.
Assuntos
Oócitos , Oogênese , Suínos , Animais , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo , Mitocôndrias , Apoptose , MamíferosRESUMO
Fusarium cerealis is a causal agent of Fusarium Head Blight in wheat, and it produces both deoxynivalenol (DON) and nivalenol (NIV). Nevertheless, the effect of environmental factors on the growth and mycotoxin production of this species has not been studied so far. The objective of this study was to investigate the impact of environmental factors on the growth and mycotoxin production of F. cerealis strains. All strains were able to grow in a wide range of water activity (aW) and temperatures, but their mycotoxin production was influenced by strain and environmental factors. NIV was produced at high aW and temperatures, while optimal conditions for DON production were observed at low aW. Interestingly, some strains were able to simultaneously produce both toxins, which could pose a more significant risk for grain contamination.