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1.
Chemosphere ; 244: 125493, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32050327

RESUMO

Zearalenone (ZEA), as a contaminant commonly found in our daily diet, has been widely studied for its toxicity. However, the exact mechanism underlying ZEA induced reproduction disorders remains unclear. Our study aimed to elucidate the underlying relationship between aberrations in the gut microbiota and the degeneration of the ovarian reserve following exposure to ZEA. Four-week-old mice were treated with different doses (0, 20, 40 µg/kg bw/day) of ZEA for 2 weeks and it was found that the primordial follicles were dramatically decreased when compared to untreated controls. Moreover, we applied metagenomic shotgun sequencing to investigate the effects of ZEA exposure on the population composition and function of gut microbiota. The results showed that the abundance of three susceptible bacterial strains, parabacteroides, bacteroides and lachnospiraceae were increased in a dose-dependent manner after ZEA exposure, whereas the bacterial glycerophospholipid metabolism pathway was greatly suppressed. Of note, utilizing LC/MS we found lysophosphatidylcholines (LPCs), important metabolites in the process of glycerophospholipid metabolism, were markedly decreased in the plasma of the ZEA treated mice. In conclusion, our findings here provide evidences that the dysfunction in gut microbiome after ZEA exposure may affect the ovarian reserve.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Reserva Ovariana/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Bactérias/efeitos dos fármacos , Feminino , Glicerofosfolipídeos/metabolismo , Lisofosfolipídeos/sangue , Camundongos , Folículo Ovariano/efeitos dos fármacos , Ovário/efeitos dos fármacos
2.
Toxicol Lett ; 323: 1-9, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31982503

RESUMO

Zearalenone (ZEA) is a prevalent non-steroidal estrogenic mycotoxin produced mainly by Fusarium contamination. Our previous study showed that ZEA induces the autophagy of Sertoli cells (SCs). However, the underlying mechanisms are still unknown. Several studies have indicated that the increasing level of cytoplasmic Ca2+ could induce autophagy through CaMKKß and AMPK pathways. Thus in order to investigate the potential mechanism underlying ZEA-induced autophagy, the activity of calmodulin-dependent kinase kinase ß(CaMKKß)and AMP-activated protein kinase (AMPK) signaling pathway in ZEA-infected TM4 cells was studied. In the present study, ZEA activated the CaMKKß and AMPK signaling pathways. The AMPK inhibitor and activator significantly inhibited and stimulated the effect of ZEA on AMPK, the transformation from LC3I to LC3II, and the distribution of LC3 dots. In addition, cytosolic calcium (Ca2+) was increased gradually with the concentration of ZEA. After treatment of ZEA-infected cells with 1, 2-bis (2-aminophenoxy) ethane-N, N, N', N'- tetraacetic acid- tetraac etoxymethyl ester (BAPTA-AM) and 2-aminoethyl diphenylborinate (2-APB), the intracellular concentration of Ca2+ reduced significantly. Also, the activities of CaMKKß and AMPK and subsequent autophagy decreased. Moreover, the antioxidant NAC significantly decreased activities of AMPK and autophagy -related protein. Therefore, it can be speculated that ROS- mediated ER-stress induced by ZEA activates AMPK via Ca2+-CaMKKß leading to autophagy in TM4 cells.


Assuntos
Proteínas Quinases Ativadas por AMP/fisiologia , Autofagia/efeitos dos fármacos , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/fisiologia , Cálcio/fisiologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Células Cultivadas , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/fisiologia , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/fisiologia
3.
J Sci Food Agric ; 100(3): 1118-1123, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31667844

RESUMO

BACKGROUND: Dairy farming feed can be contaminated with mycotoxins, affecting animals' health and milk quality. Dairy farming is also prone to occupational exposure to mycotoxins, and feed is recognized as a source of contamination in the workplace. An exploratory study was developed in a dairy farm located in Portugal intending to assess the mycotoxins present in the feed. RESULTS: All the samples analyzed presented contamination by at least two mycotoxins and up to a maximum of 13 mycotoxins in the same sample. Zearalenone (ZEA) was detected in all the samples (n = 10) followed by deoxynivalenol (DON), which was reported in eight samples, and ochratoxin A (OTA), reported in five samples. CONCLUSION: The results point to the possible contamination of milk by several mycotoxins and raise the possibility of occupational exposure to mycotoxins due to feed contamination. An adequate One Health approach for dairy production should address these issues through effective preventive actions such as avoiding the use of feed contaminated with mycotoxins. This represents an important challenge due to climate change. It requires proper attention and accurate management measures. © 2019 Society of Chemical Industry.


Assuntos
Doenças dos Trabalhadores Agrícolas/etiologia , Ração Animal/análise , Leite/química , Micotoxinas/análise , Exposição Ocupacional/efeitos adversos , Doenças dos Trabalhadores Agrícolas/prevenção & controle , Animais , Bovinos , Fazendeiros/estatística & dados numéricos , Fazendas , Contaminação de Alimentos/análise , Humanos , Micotoxinas/toxicidade , Exposição Ocupacional/análise , Exposição Ocupacional/prevenção & controle , Ocratoxinas/análise , Ocratoxinas/toxicidade , Portugal , Zearalenona/análise , Zearalenona/toxicidade
4.
Toxicol Lett ; 319: 242-249, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31733320

RESUMO

Humans are typically exposed to mixtures of substances, whereby their bioactivity can be significantly altered by co-occurring compounds. Thus, over the last years, research on combinatory effects has gained increasing attention. In particular, several xenoestrogens have been recently reported to interact synergistically, among them alternariol (AOH) and zearalenone (ZEN), two toxins produced by molds which contaminate crops or food commodities. Bisphenol A (BPA) is a potential food contaminant arising from its use in plastics and represents a well-known xenoestrogen, acting as an endocrine disruptor. However, little research was yet conducted on its impact on the bioactivity of other xenoestrogens, and vice versa. Thus, in this study, we focused on combinatory estrogenic effects of BPA with AOH and ZEN in Ishikawa cells, which represent a well-established, estrogen-sensitive human cell model. Estrogenic stimuli of the single compounds and binary combinations in constant concentration ratios were measured by assessing the activity of alkaline phosphatase, a natural reporter gene for estrogen receptor activation. In parallel, cytotoxicity was monitored by neutral red assay. For statistical analysis of combinatory effects the "combination index" model was applied. In combination with ZEN, BPA was found to cause additive estrogenic effects. Mixtures of BPA with AOH expressed moderately antagonistic to nearly additive combinatory effects, depending on the concentration ratio. Although no synergistic effects were measured in the applied chemical mixtures, additive estrogenic stimuli were observed, underlining the importance to consider the cumulative impact of endocrine active factors out of different sources and structural classes.


Assuntos
Compostos Benzidrílicos/toxicidade , Endométrio/efeitos dos fármacos , Estrogênios/toxicidade , Lactonas/toxicidade , Micotoxinas/toxicidade , Fenóis/toxicidade , Zearalenona/toxicidade , Fosfatase Alcalina/análise , Fosfatase Alcalina/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Interações de Medicamentos , Disruptores Endócrinos/toxicidade , Endométrio/citologia , Feminino , Humanos
5.
Chemosphere ; 240: 124948, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31726616

RESUMO

Zearalenone is a xenoestrogenic mycotoxin produced by Fusarium species. High exposure with zearalenone induces reproductive disorders worldwide. Cyclodextrins are ring-shaped host molecules built up from glucose units. The apolar cavity of cyclodextrins can entrap so-called guest molecules. The formation of highly stable host-guest type complexes with cyclodextrins can decrease the biological effect of the guest molecule. Therefore, cyclodextrins may be suitable to decrease the toxicity of some xenobiotics even after the exposure. In this study, the protective effect of beta-cyclodextrins against zearalenone-induced toxicity was investigated in HeLa cells and zebrafish embryos. Fluorescence spectroscopic studies demonstrated the formation of stable complexes of zearalenone with sulfobutyl-, methyl-, and succinyl-methyl-substituted beta-cyclodextrins at pH 7.4 (K = 1.4-4.7 × 104 L/mol). These chemically modified cyclodextrins considerably decreased or even abolished the zearalenone-induced loss of cell viability in HeLa cells and mortality in zebrafish embryos. Furthermore, the sublethal effects of zearalenone were also significantly alleviated by the co-treatment with beta-cyclodextrins. To test the estrogenic effect of the mycotoxin, a transgenic bioindicator zebrafish model (Tg(vtg1:mCherry)) was also applied. Our results suggest that the zearalenone-induced vitellogenin production is partly suppressed by the hepatotoxicity of zearalenone in zebrafish. This study demonstrates that the formation of stable zearalenone-cyclodextrin complexes can strongly decrease or even abolish the zearalenone-induced toxicity, both in vitro and in vivo. Therefore, cyclodextrins appear as promising new mycotoxin binders.


Assuntos
Substâncias Protetoras/farmacologia , Zearalenona/toxicidade , Peixe-Zebra/embriologia , beta-Ciclodextrinas/farmacologia , Animais , Ciclodextrinas/química , Estrogênios/farmacologia , Células HeLa/efeitos dos fármacos , Humanos , Micotoxinas/metabolismo , Substâncias Protetoras/química , Reprodução/efeitos dos fármacos , beta-Ciclodextrinas/química , beta-Ciclodextrinas/metabolismo
6.
J Agric Food Chem ; 67(43): 12117-12128, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31587554

RESUMO

Zearalenone (ZEA), a pathogenic toxin produced by Fusarium, is widely detected in moldy feed materials. Previous studies have reported that ZEA exerts a harmful influence on animal reproductive systems; however, its effects on the changes of long noncoding RNAs (lncRNAs) remain unclear. Here, tackling this question, we performed RNA sequencing on porcine granulosa cells (GCs) after being exposed to 10 and 30 µM ZEA in vitro. The results showed that ZEA exposure observably changed the expression of lncRNAs in porcine GCs and increased the rate of apoptosis. Furthermore, Gene Ontology analysis showed that ZEA exposure induced variation of the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway in porcine GCs. To verify our bioinformatics analysis, western blotting and immunofluorescence analysis were performed and the results demonstrated that porcine GCs after ZEA exposure increased the expression of key proteins in the JAK2-STAT3 signaling pathway. Further bioinformatics analysis found that MSTRG.22680 and MSTRG.23882 played a pivotal role in activating the JAK2-STAT3 signaling pathway. To summarize, our results throw light on the fact that ZEA exposure dramatically increases the apoptosis of porcine GCs and alters the expression of lncRNAs that play an antiapoptotic role in porcine GCs via activating the JAK2-STAT3 signaling pathway.


Assuntos
Apoptose/efeitos dos fármacos , Células da Granulosa/efeitos dos fármacos , Janus Quinase 2/metabolismo , RNA Longo não Codificante/genética , Fator de Transcrição STAT3/metabolismo , Zearalenona/toxicidade , Animais , Feminino , Células da Granulosa/citologia , Células da Granulosa/metabolismo , Janus Quinase 2/genética , RNA Longo não Codificante/metabolismo , Fator de Transcrição STAT3/genética , Transdução de Sinais/efeitos dos fármacos , Suínos
7.
Arq. bras. med. vet. zootec. (Online) ; 71(5): 1659-1668, set.-out. 2019. tab, graf
Artigo em Português | LILACS, VETINDEX | ID: biblio-1038665

RESUMO

Objetivou-se avaliar as variáveis micotoxicológicas e nutricionais de híbridos de milho com diferentes características que influenciam no custo da ração para frangos de corte. Foram avaliados 26 híbridos de milho geneticamente modificados nas safrinhas de 2016 e 2017, com diferentes germoplasmas, textura de endosperma e duração do ciclo. Nos híbridos, foram avaliados grãos avariados, fumonisinas (B1+B2) (FUM), aflatoxinas (B1+B2+G1+G2) (AFLA), zearalenona (ZEA), deoxinivalenol (DON), umidade, proteína bruta (PB), energia metabolizável aparente corrigida para balanço de nitrogênio (EMAn), aminoácidos digestíveis para aves (lisina, metionina, cistina e treonina) e o respectivo custo da ração inicial para frangos de corte, que foi calculada pelo custo mínimo. A prevalência de FUM, AFLA, ZEA e DON foi de 90, 17, 33 e 0%, com médias de 3067, 1, 38 e 0µg/kg nos dois anos, respectivamente. A média de EMAn e PB foi de 3264kcal/kg e 8,02%, respectivamente, e diferiu (P<0,05) nos dois anos. O custo da ração foi influenciado significativamente (P<0,05) por FUM, PB, EMAn nos dois anos. Híbridos com tecnologia Viptera apresentam menor concentração por FUM e menor custo da ração. Híbridos de ciclo precoce têm menor concentração de FUM, maiores percentuais de PB e de aminoácidos digestíveis e menor custo da ração.(AU)


The objective of this study was to evaluate the mycotoxicological and nutritional variables of maize hybrids with different characteristics that influence the broiler chicken's feed costs. In 2016 and 2017 winter crops, 26 genetically modified hybrids of maize with different germplasm, endosperm texture and cycle duration were evaluated. The analyzed variables were damaged grains, fumonisins (B 1 +B 2 ) (FUM), aflatoxins (B 1 +B 2 +G 1 +G 2 ) (AFLA), zearalenone (ZEA), deoxynivalenol (DON), moisture, crude protein (CP), apparent metabolizable energy corrected for nitrogen balance (AMEn), digestible amino acids for poultry (lysine, methionine, cystine and threonine) and the respective cost of the initial feed for broiler chickens calculated at the minimum cost. The prevalence of FUM, AFLA, ZEA and DON was 90, 17, 33 and 0%, with means of 3067, 1, 38 and 0µg/kg in the two years, respectively. The mean of AMEn and CP was 3264kcal/kg and 8.02%, respectively, and differed (P< 0.05) in the two years. The feed cost was significantly influenced (P<0.05) by FUM, PB, AMEn in two years. Hybrids with Viptera technology show lower concentration per FUM and lower feed cost. Early cycle hybrids have lower concentrations of FUM, higher percentages of CP and digestible amino acids, and lower feed costs.(AU)


Assuntos
Zea mays/genética , Zea mays/toxicidade , Ração Animal/toxicidade , Micotoxinas/análise , Micotoxinas/toxicidade , Zearalenona/toxicidade , Aflatoxinas/toxicidade , Fumonisinas/toxicidade
8.
Food Chem ; 301: 125281, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31382109

RESUMO

The need for safe and quality food, free from the presence of hazardous contaminants such as mycotoxins is an on-going and complex challenge. Cold atmospheric pressure plasma (CAPP) has the potential to contribute to achieving this goal. Decontamination efficacy of CAPP against six of the most common mycotoxins found in foods and feedstuffs was assessed herein. Concentration reduction of up to 66% was achieved in maize for both aflatoxin B1 and fumonisin B1. Degradation products were detected only in the case of aflatoxin B1 and zearalenone and were tested on human hepatocarcinoma cells with no increase in cytotoxicity observed. Analysis of treated maize revealed substantial changes to small molecular mass components of the matrix. While CAPP shows promise in terms of mycotoxin detoxification important questions concerning potential changes to the nutritional and safety status of the food matrix require further investigations.


Assuntos
Descontaminação/métodos , Contaminação de Alimentos/análise , Micotoxinas/química , Gases em Plasma/química , Aflatoxina B1/análise , Aflatoxina B1/química , Aflatoxina B1/toxicidade , Fumonisinas/análise , Fumonisinas/química , Fumonisinas/toxicidade , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Humanos , Micotoxinas/análise , Micotoxinas/toxicidade , Zea mays/química , Zearalenona/análise , Zearalenona/química , Zearalenona/toxicidade
9.
Toxicol Lett ; 315: 31-38, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31419471

RESUMO

Endocrine disruptor zearalenone (ZEA) has been found to damage the reproductive system especially spermatogenesis. In our previous report, we have found that low dose (lower than No-Observed Effect Level, NOEL) ZEA exposure disturbed mouse spermatogenesis and diminished mouse semen quality. The purpose of current investigation was to explore the underlying mechanisms of pubertal low dose ZEA exposure upsetting spermatogenesis. And it was demonstrated that pubertal low dose ZEA exposure disrupted the meiosis process and the important genetic pathways to inhibit the spermatogenesis and even to diminish the semen quality with the decrease in spermatozoa motility and concentration. The DNA methylation markers 5mC and 5hmC were decreased, the histone methylation marker H3K27 was increased, at the same time estrogen receptor alpha was diminished in mouse testis after pubertal low dose ZEA exposure. The data indicate that the disruption in spermatogenesis by pubertal low dose ZEA exposure may be through the alterations in genetic and epigenetic pathways, and the interactions with estrogen receptor signaling pathway. Therefore, we should pay great attention on ZEA exposure to reduce its adverse impacts on male reproductive health.


Assuntos
Divisão Celular/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Receptor alfa de Estrogênio/efeitos dos fármacos , Motilidade Espermática/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatogênese/genética , Zearalenona/toxicidade , Adolescente , Animais , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Transdução de Sinais/efeitos dos fármacos
10.
Food Chem Toxicol ; 131: 110599, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31247258

RESUMO

This paper describes a methodology for hazard assessment of groups of related substances for which toxicity data are insufficient, and which utilises, next to conventional toxicological assessments and mechanistic information, the derivation of relative toxicity potency factors (RPFs). Zearalenone (ZEN) and T-2 toxin (T2) and HT-2 toxin (HT2) and their modified forms have been used as examples. A tolerable daily intake (TDI) for ZEN of 0.25 µg/kg bw was established. In vitro and in vivo studies suggested that modified forms of ZEN act via the same mode of action as ZEN (oestrogenicity). Results from in vivo uterotrophic assays were used to establish RPFs, allowing inclusion the different modified forms in a group TDI with ZEN. A TDI for the sum of T2/HT2 of 0.02 µg/kg bw per day and an acute reference dose (ARfD) of 0.3 µg/kg bw for the sum of T2/HT2 was established. In vitro studies show that phase I metabolites of T2/HT2 act via a similar mode of action as their parent compounds, namely protein synthesis inhibition with immune- and haematotoxicity. The phase I metabolites as well as conjugates of T2/HT2 and their phase I metabolites can be included in a group TDI with T2/HT2 applying RPFs.


Assuntos
Toxina T-2/análogos & derivados , Zearalenona/toxicidade , Animais , Estrogênios/toxicidade , Humanos , Nível de Efeito Adverso não Observado , Medição de Risco/métodos , Toxina T-2/toxicidade , Zearalenona/análogos & derivados
11.
Food Chem Toxicol ; 131: 110527, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31173817

RESUMO

Zearalenone (ZEA) can widely contaminate crops and agricultural products. The ingestion of ZEA-contaminated food or feed affects the integrity and functions of the intestines. In this study, we aimed to find the potential protective mechanism against ZEA ingestion. We found that ZEA induced cell death in IPEC-J2 cells. Meanwhile, the cytoprotective autophagy was activated in ZEA-treated cells. Further studies demonstrated that a p38/MAPK inhibitor down-regulated autophagy and increased cell death compared to those of the controls. Furthermore, ZEA could induce the accumulation of ROS, and eliminating ROS with NAC resulted in a decline in cell death, p38/MAPK phosphorylation, and the expression of LC3-II compared to those of ZEA-group. In addition, cytochrome P450 reductase (CYPOR) was significantly increased in ZEA-treated cells compared to that in the controls, and an inhibitor of CYPOR decreased ROS levels and mitigated cell death compared to those of the ZEA-group. More importantly, we found that blocking both p38/MAPK signalling and autophagy could enhance CYPOR expression and elevate ROS levels. Overall, our study indicated that the p38/MAPK pathway could activate protective autophagy in response to the CYPOR-dependent oxidative stress that was induced by ZEA in IPEC-J2 cells.


Assuntos
Autofagia/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NADPH-Ferri-Hemoproteína Redutase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Zearalenona/toxicidade , Acetilcisteína/farmacologia , Animais , Células Epiteliais/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Intestinos/efeitos dos fármacos , MAP Quinase Quinase 4/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Suínos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-31035709

RESUMO

Zearalenone (ZEA) is a non-steroidal estrogen mycotoxin produced by several Gibberella and Fusarium species. Accumulating evidence has indicated that ZEA strongly stimulates cell proliferation. However the detailed molecular and cellular mechanisms of ZEA-mediated induction of cell proliferation have not yet been completely explained. The aim of this study was to detect the role of miRNAs in ZEA-mediated induction of cell proliferation. The effects of ZEA on cell proliferation were assessed using a cell counting kit assay and xCELLigence system. Micro-RNA sequencing was performed after treatment of TM3 cells with ZEA (0.01 µmol/L) for different time periods (0, 2, 6 and 18 h). Cell function and pathway analysis of the miRNA target genes were performed by Ingenuity Pathway Analysis (IPA). We found that ZEA promotes TM3 cell proliferation at low concentrations. miRNA sequenceing revealed 66 differentially expressed miRNAs in ZEA-treated cells in comparison to the untreated control ( p < 0.05). The miRNA sequencing indicated that compared to control group, there were 66 miRNAs significant change (p < 0.05) in ZEA-treated groups. IPA analysis showed that the predicated miRNAs target gene involved in cell Bio-functions including cell cycle, growth and proliferation, and in signaling pathways including MAPK and RAS-RAF-MEK-ERK pathways. Results from flow cytometry and Western Blot analysis validated the predictions that ZEA can affect cell cycle, and the MAPK signaling pathway. Taking these together, the cell proliferation induced ZEA is regulated by miRNAs. The results shed light on the molecular and cellular mechanisms for the mediation of ZEA to induce proliferation.


Assuntos
Proliferação de Células/efeitos dos fármacos , MicroRNAs/metabolismo , Zearalenona/toxicidade , Animais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Estrogênios Conjugados (USP) , Regulação da Expressão Gênica/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , MicroRNAs/genética , Transdução de Sinais/efeitos dos fármacos
13.
Basic Clin Pharmacol Toxicol ; 125(4): 382-393, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31058416

RESUMO

Zearalenone (ZEA), a F-2 mycotoxin produced by Fusarium, has been found to be an endocrine disruptor through oestrogen receptor signalling pathway to impair spermatogenesis. The disruption on reproductive systems by ZEA exposure might be transgenerational. In our previous report, we have found that low dose (lower than no-observed effect level, NOEL) of ZEA impaired mouse spermatogenesis and decreased mouse semen quality. The purpose of the current investigation was to explore the impacts of low-dose ZEA on spermatogenesis in the offspring after prenatal exposure and the underlying mechanisms. And it demonstrated that prenatal low-dose ZEA exposure disrupted the meiosis process to inhibit the spermatogenesis in offspring and even to diminish the semen quality by the decrease in spermatozoa motility and concentration. The DNA methylation marker 5hmC was decreased, the histone methylation markers H3K9 and H3K27 were elevated, and oestrogen receptor alpha was reduced in the offspring testis after prenatal low-dose ZEA exposure. The data suggest that the disruption in spermatogenesis by prenatal low-dose ZEA exposure may be through the modifications on epigenetic pathways (DNA methylation and histone methylation) and the interactions with oestrogen receptor signalling pathway. Moreover, in the current study, the male offspring were indirectly exposed to low-dose ZEA through placenta and the spermatogenesis in offspring was disrupted which suggested that the toxicity of ZEA on reproductive systems was very severe. Therefore, we strongly recommend that greater attention should be paid to this mycotoxin to minimize its adverse impact on human spermatogenesis.


Assuntos
Disruptores Endócrinos/toxicidade , Epigênese Genética/efeitos dos fármacos , Exposição Materna/efeitos adversos , Espermatogênese/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Animais Recém-Nascidos , Metilação de DNA/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Código das Histonas/efeitos dos fármacos , Humanos , Infertilidade Masculina/induzido quimicamente , Masculino , Troca Materno-Fetal , Camundongos , Camundongos Endogâmicos ICR , Nível de Efeito Adverso não Observado , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Análise do Sêmen , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Motilidade Espermática/efeitos dos fármacos , Espermatogênese/genética , Testículo/efeitos dos fármacos , Testículo/patologia
14.
Toxins (Basel) ; 11(5)2019 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-31137638

RESUMO

Zearalenone is a frequent contaminant of cereals and their by-products in regions with a temperate climate. This toxic molecule is produced naturally by Fusarium fungi in crops. The aim of this study was to determine the influence of low zearalenone doses (LOAEL, NOAEL and MABEL) on the intestinal microbiome of gilts on different days of exposure (days 7, 21 and 42). Intestinal contents were sampled from the duodenal cap, the third part of the duodenum, jejunum, caecum and the descending colon. The experiment was performed on 60 clinically healthy gilts with average BW of 14.5 ± 2 kg, divided into three experimental groups and a control group. Group ZEN5 animals were orally administered ZEN at 5 µg /kg BW, group ZEN10-10 µg ZEN/kg BW and group ZEN15-15 µg ZEN/kg BW. Five gilts from every group were euthanized on analytical dates 1, 2 and 3. Differences in the log values of microbial counts, mainly Escherichia coli and Enterococcus faecalis, were observed between the proximal and distal segments of the intestinal tract on different analytical dates as well as in the entire intestinal tract. Zearalenone affected the colony counts of intestinal microbiota rather than microbiome diversity, and its effect was greatest in groups ZEN10 and ZEN15. Microbial colony counts were similar in groups ZEN5 and C. In the analysed mycobiome, ZEN exerted a stimulatory effect on the log values of yeast and mould counts in all intestinal segments, in particular in the colon, and the greatest increase was noted on the first analytical date.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Bactérias/efeitos dos fármacos , Carga Bacteriana , Feminino , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Suínos
15.
Toxins (Basel) ; 11(5)2019 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-31137857

RESUMO

Zearalenone (ZEA) is an estrogenic and ochratoxin A (OTA) is a hepatotoxic Fusarium mycotoxin commonly seen in cereals and fruits products. No previous investigation has studied on a single platform for the multi degradation mycotoxin. The current study aimed to investigate the bifunctional activity of a novel fusion recombinant. We have generated a recombinant fusion enzyme (ZHDCP) by combining two single genes named zearalenone hydrolase (ZHD) and carboxypeptidase (CP) in frame deletion by crossover polymerase chain reaction (PCR). We identified enzymatic properties and cell cytotoxicity assay of ZHDCP enzyme. Our findings have demonstrated that ZEA was completely degraded to the non-toxic product in 2 h by ZHDCP enzyme at an optimum pH of 7 and a temperature of 35 °C. For the first time, it was found out that ZEA 60% was degraded by CP degrades in 48 h. Fusion ZHDCP and CP enzyme were able to degrade 100% OTA in 30 min at pH 7 and temperature 30 °C. ZEA- and OTA-induced cell death and increased cell apoptosis rate and regulated mRNA expression of Sirt1, Bax, Bcl2, Caspase3, TNFα, and IL6 genes. Our novel findings demonstrated that the fusion enzyme ZHDCP possess bifunctional activity (degrade OTA and ZEA), and it could be used to degrade more mycotoxins.


Assuntos
Carboxipeptidases/química , Hidrolases/química , Enzimas Multifuncionais/química , Ocratoxinas/química , Proteínas Recombinantes de Fusão/química , Zearalenona/química , Carboxipeptidases/genética , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Hidrolases/genética , Ocratoxinas/toxicidade , Zearalenona/toxicidade
16.
Toxicon ; 165: 13-21, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31004610

RESUMO

The mycotoxin zearalenone (ZEA) has strong estrogenic effects and elicits reproductive toxicity. Chrysin is a natural flavonoid found in many plant and has a broad range of pharmacological activities, including anticancer, antioxidant and anti-inflammatory. The present study aimed to investigate the potential protective effects of chrysin against ZEA toxicity. Mice received chrysin (5 or 20 mg/kg; i.g.) for ten days, and then received a single injection of ZEA (40 mg/kg). Two days thereafter, blood and testes were collected. ZEA decreased number and motility of sperm, plasma testosterone levels, enzymatic (glutathione peroxidase, glutathione reductase, glutathione-S-transferase) and non-enzimatic defenses (reduced glutathione). Moreover, ZEA increased 4-hydroxynonenal and 8-hydroxy-2'-deoxyguanosine levels, myeloperoxidase activity and levels of proinflammatory cytokines (interleukins-1ß and 6, tumor necrosis factor alpha). ZEA also decreased levels of anti-inflammatory cytokine interleukin-10 and increased activity of caspases 3 and 9. Chrysin treatment increased the number and motility of sperm, testosterone levels, restored antioxidant defenses and reduced the inflammation and apoptosis process. In summary, chrysin attenuated the toxic effects caused by ZEA in blood and testes of mice, suggesting a potential preventive treatment against the deleterious effects of ZEA.


Assuntos
Fertilidade/efeitos dos fármacos , Flavonoides/farmacologia , Substâncias Protetoras/farmacologia , Zearalenona/toxicidade , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Flavonoides/química , Masculino , Camundongos , Motilidade Espermática/efeitos dos fármacos , Testosterona/sangue
17.
J Environ Sci Health B ; 54(6): 514-524, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31014207

RESUMO

Humans and animals can be exposed to mixtures of chemicals from food and water, especially during disasters such as extended droughts, hurricanes and floods. Drought stress facilitates the occurrence of mycotoxins such as aflatoxins B1 (AfB1) and zearalenone (ZEN), while hurricanes and floods can mobilize toxic soil and sediments containing important pesticides (such as glyphosate). To address this problem in food, feed and water, we developed broad-acting, clay-based enterosorbents that can reduce toxin exposures when included in the diet. In this study, we processed sodium and calcium montmorillonite clays with high concentrations of sulfuric acid to increase surface areas and porosities, and conducted equilibrium isothermal analyses and dosimetry studies to derive binding parameters and gain insight into: (1) surface capacities and affinities, (2) potential mechanisms of sorption, (3) thermodynamics (enthalpy) of toxin/surface interactions and (4) estimated dose of sorbent required to maintain toxin threshold limits. We have also used a toxin-sensitive living organism (Hydra vulgaris) to predict the safety and efficacy of newly developed sorbents. Our results indicated that acid processed montmorillonites were effective sorbents for AfB1, ZEN and glyphosate, with high capacity and tight binding, and effectively protected hydra against individual toxins, as well as mixtures of mycotoxins.


Assuntos
Bentonita/química , Exposição Ambiental/prevenção & controle , Aflatoxina B1/química , Aflatoxina B1/metabolismo , Aflatoxina B1/toxicidade , Animais , Argila , Desastres , Glicina/análogos & derivados , Glicina/química , Humanos , Hydra/efeitos dos fármacos , Ácidos Sulfúricos/química , Termodinâmica , Água/química , Zearalenona/química , Zearalenona/metabolismo , Zearalenona/toxicidade
18.
Food Chem Toxicol ; 126: 262-276, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30825585

RESUMO

Zearalenone (ZEA), a non-steroidal estrogen mycotoxin produced by several species of Fusarium fungi, can be metabolized into many other derivatives by microorganisms, plants, animals and humans. It can affect mammalian reproductive capability by impacting the synthesis and secretion of sex hormones, including testosterone, estradiol and progesterone. This review summarizes the mechanisms in which ZEA and its derivatives disturb the synthesis and secretion of sex steroid hormones. Because of its structural analogy to estrogen, ZEA and its derivatives can exert a variety of estrogen-like effects and engage in estrogen negative feedback regulation, which can result in mediating the production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the pituitary gland. ZEA and its derivatives can ultimately reduce the number of Leydig cells and granulosa cells by inducing oxidative stress, endoplasmic reticulum (ER) stress, cell cycle arrest, cell apoptosis, and cell regeneration delay. Additionally, they can disrupt the mitochondrial structure and influence mitochondrial functions through overproduction of reactive oxygen species (ROS) and aberrant autophagy signaling ways. Finally, ZEA and its derivatives can disturb the expressions and activities of the related steroidogenic enzymes through cross talking between membrane and nuclear estrogen receptors.


Assuntos
Hormônios Esteroides Gonadais/biossíntese , Mamíferos/fisiologia , Zearalenona/química , Zearalenona/toxicidade , Animais , Feminino , Hormônios Esteroides Gonadais/metabolismo , Humanos , Masculino , Reprodução/efeitos dos fármacos
19.
Ecotoxicol Environ Saf ; 175: 263-271, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-30903882

RESUMO

Zearalenone (ZEA) is a phenolic resorcylic acid lactone mycotoxin produced by several Fusarium species that grow on temperate and tropical crops. The number of reports documenting the immunotoxic effects of ZEA is increasing, but the underlying mechanism is not clear. The purpose of this study was to investigate the effects of ZEA on T cell chemotaxis and evaluate changes in adhesion and migration proteins associated with this process. Specifically, T cells were isolated from BALB/C mouse splenic lymphocytes, activated by concanavalin A (Con A), and then exposed to different concentrations of ZEA. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used observe the ultrastructural changes inside the cell and on the cell surface, respectively. The transwell migration assay was used to evaluate the effect of ZEA on T cell chemotaxis in the presence of CCL19 or CCL21. A confocal 3D laser was used to capture the morphology of perforated cells and western blot was used to detect the expression of proteins associated with cell migration and adhesion. Additionally, we used flow cytometry to examine the expression of chemokine receptors on T cells. Finally, the chemokine (RANTES and MIP-1α) levels secreted by T cells were assessed using cytometric bead array. Overall, our data showed that treatment with ZEA caused ultrastructural damage on the surface as well as inside of T cells. Moreover, ZEA inhibited T cell chemotaxis which was mediated by CCL19 or CCL21 and disrupted the balance of T cell subtypes. The expression of T cell adhesion and migration proteins was also inhibited by ZEA. The expression of T cell chemokine receptor as well as secretion of RANTES and MIP-1α by T cells was suppressed after ZEA treatment. In summary, our results indicate that ZEA reduced the chemotactic effect of T cells mediated by chemokines, which was likely linked to the inhibition of T cell motility and accompanied by decreased expression of adhesion and migration proteins.


Assuntos
Adesão Celular/efeitos dos fármacos , Quimiocinas/biossíntese , Quimiotaxia/efeitos dos fármacos , Receptores de Quimiocinas/biossíntese , Linfócitos T/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Movimento Celular/efeitos dos fármacos , Quimiocina CCL19/biossíntese , Quimiocina CCL21/biossíntese , Quimiocina CCL5/biossíntese , Citometria de Fluxo , Humanos , Camundongos Endogâmicos BALB C , Linfócitos T/imunologia
20.
Toxicol Lett ; 309: 1-9, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30904571

RESUMO

Aflatoxin M1 (AFM1), ochratoxin A (OTA), and zearalenone (ZEA) are mycotoxins commonly found in milk. Mycotoxin contamination has caused food safety concerns worldwide since most of the toxic effects in humans are serious. The combined toxic effects of these mycotoxins on intestinal epithelial cells have not been reported. Herein, we investigated the combined effects of AFM1, OTA, and ZEA on intestinal integrity and define the underlying mechanisms(s) of their effects in Caco-2/HT29-MTX co-cultures. Our results showed that the mixtures of AFM1 + OTA, AFM1 + ZEA, and AFM1 + ZEA + OTA significantly increased epithelial permeability. Immunofluorescence analysis and transmission electron microscopy revealed that mycotoxins altered TJ proteins morphology and disrupted their structures. Also, the present study showed that mixtures of mycotoxins significantly modulated MUC5AC and MUC5B mRNA levels and protein secretion. This study demonstrated that the effects of mixtures of mycotoxins on intestinal barrier function were more significant than AFM1 alone. More importantly, the damage of intestinal integrity caused by mycotoxins was correlated to the change of the TJ proteins location and the decrease of mucin secretion. Mixtures of AFM1, OTA, and ZEA in food might pose a health risk to consumers, particularly in children, and toxin risks should be considered.


Assuntos
Aflatoxina M1/toxicidade , Mucosa Intestinal/efeitos dos fármacos , Mucinas/metabolismo , Ocratoxinas/toxicidade , Zearalenona/toxicidade , Células CACO-2 , Técnicas de Cocultura , Contaminação de Alimentos , Células HT29 , Humanos , Mucosa Intestinal/metabolismo , Mucina-5AC/análise , Mucina-5AC/genética , Mucina-2/análise , Mucina-2/genética , Mucina-5B/análise , Mucina-5B/genética , Mucinas/genética , Permeabilidade , RNA Mensageiro/análise , Proteínas de Junções Íntimas/análise
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