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1.
Toxicon ; 189: 39-44, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33197481

RESUMO

The study aimed to examine the effects of zearalenone on genital organ development, serum immunoglobulin, antioxidant capacity, sex hormones and liver function of prepubertal gilts. Forty-eight prepubertal gilts (Landrace × Yorkshire) were randomly divided into three treatment (T1, T2 and T3) groups and a control group (12 replicates per group, 1 gilt per replicate). Prepubertal gilts in the control group were fed with basal diet, and those in T1, T2 and T3 groups were fed with basal diets supplemented with 200 µg/kg, 800 µg/kg and 1600 µg/kg zearalenone during the experiment period, which lasted for 14 d. Feed intake was counted and vulvar area was measured. The blood samples were collected from the anterior vena cava of 6 prepubertal gilts in each group, and immunoglobulins, antioxidant indexes, inflammatory cytokines, genital hormones, and biochemical indexes were analyzed by enzyme-linked immunosorbent assay. The results showed that the average daily feed intake of prepubertal gilts in each group had no significant change (p > 0.05). On 14 d, compared with the control group, the vulva area of prepubertal gilts in each treatment group was significantly increased (p < 0.05). Compared with the control group, the serum immunoglobulin G content in the T3 group was significantly reduced (p < 0.05). The activities of total antioxidant capacity and the superoxide dismutase of serum in the T3 group were significantly reduced (p < 0.05). Compared with the control group, the serum interleukin-4 content in each test group were extremely significantly increased (p < 0.01). The serum contents of luteinizing hormone in the T2 and T3 groups and estradiol in the T3 group were significantly reduced (p < 0.05) than that of control group. Compared with the control group, the activity of aspartate aminotransferase in T3 group was significantly increased (p < 0.05). In conclusion, zearalenone has no significantly effect on the feed intake of prepubertal gilts, but it can reduce its serum immunoglobulin contents and antioxidant properties, disrupt the secretion of sex hormones, increase the vulva area, produce reproductive toxicity and cause liver damage. Therefore, in pig production, the use of antimould reagent together with products of immunity-boosting, antioxidant, anti-inflammatory and hepatoprotective may enhance protection.


Assuntos
Zearalenona/toxicidade , Animais , Aspartato Aminotransferases , Estradiol , Feminino , Genitália , Imunoglobulinas , Fígado , Reprodução , Sus scrofa , Suínos , Zearalenona/farmacologia
2.
Ecotoxicol Environ Saf ; 207: 111511, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254391

RESUMO

Decidualization, which endows the endometrium competency to adopt developing embryo and maintain appropriate milieu for following growth, is a pivotal process for human pregnancy. The delicate collaboration between ovarian steroid hormones estrogen and progesterone governs the process of decidualization and subsequent establishment of embryo implantation. Mycotoxin zearalenone (ZEA) is well known as endocrine disruptor due to its potent estrogenic activity. In this study, we investigated effects of ZEA on decidualization of human endometrial stromal cells. Results indicated that ZEA exhibited its inhibitory action through nuclear translocation of ERα. ZEA exposure led to dampened progress of decidualization, which could be attenuated by estrogen receptor antagonist. Notably, resveratrol (RSV) administration restored impaired decidualization process by induction of anti-oxidative gene glutathione peroxidase 3 (GPX3). This study provides novel insights into the mechanism underlying adverse effects of ZEA in human decidual stromal cells and suggests RSV a potential therapeutic candidate to alleviate ZEA-induced cytotoxicity during decidualization.


Assuntos
Disruptores Endócrinos/toxicidade , Estrogênios não Esteroides/toxicidade , Substâncias Protetoras/farmacologia , Resveratrol/farmacologia , Zearalenona/toxicidade , Células Cultivadas , Decídua/efeitos dos fármacos , Implantação do Embrião/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Receptor alfa de Estrogênio , Estrogênios/farmacologia , Feminino , Humanos , Gravidez , Progesterona/farmacologia , Células Estromais/efeitos dos fármacos
3.
Wei Sheng Yan Jiu ; 49(5): 840-872, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33070833

RESUMO

OBJECTIVE: To analyze the zearalenone(ZEN) level in coix seed, and assess the risk of dietary exposure of ZEN in coix seed in Shanghai. METHODS: The ZEN contents of 147 coix seed samples collected in Shanghai were determined. The consumption data of 730 adults in Shanghai was collected by questionnaire survey with random sampling method. Dietary intake of ZEN from coix seed in Shanghai was simulated by Monte Carlo simulation. RESULTS: The total detection rate of ZEN in coix seed was 69. 39 %(102/147), with the content range of <1. 0-9361 µg/kg and the average value of 327. 7 µg/kg. The average exposure level of populations to ZEN in coix seed was 0. 0216 µg/(kg·d), which was much lower than the tolerable daily intake(TDI). The high exposure level(P95) of populations to ZEN in coix seed was 0. 0609 µg/(kg·d), which accounted for about 24% of TDI. There were about 1. 1% people with the dietary exposure to ZEN exceeding TDI on the basis of the ZEN contents in coix seed and consumption data of coix seed in Shanghai. CONCLUSION: The health risk of ZEN exposure of coix seed in Shanghai population is lower when taking coix seed regularly, and there are potential health risks when taking coix seed highly contaminated with ZEN at a higher dose for a long time.


Assuntos
Coix , Zearalenona , China , Exposição Dietética , Contaminação de Alimentos/análise , Sementes/química , Zearalenona/análise , Zearalenona/toxicidade
4.
Toxicol Lett ; 334: 44-52, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32956828

RESUMO

The co-presence of mycotoxins from fungi of the genus Fusarium is a common fact in raw food and food products, as trace levels of them or their metabolites can be detected, unless safety practices during manufacturing are carried out. Zearalenone (ZEA), its metabolites α-zearalenol (α-ZEL) and ß-zearalenol (ß-ZEL) and, beauvericin (BEA) are co/present in cereals, fruits or their products which is a mixture that consumer are exposed and never evaluated in neuronal cells. In this study the role of oxidative stress and intracellular defense systems was assessed by evaluating reactive oxygen species (ROS) generation and glutathione (GSH) ratio activity in a human neuroblastoma cell line, SH-SY5Y cells, treated individually and combined with α-ZEL, ß-ZEL and BEA. It was further examined the expression of genes involved in cell apoptosis (CASP3, BAX, BCL2) and receptors of (endogenous or exogenous) estrogens (ERß and GPER1), by RT-PCR in those same conditions. These results demonstrated elevated ROS levels in combinations where α-ZEL was involved (2.8- to 8-fold compared to control); however, no significant difference in ROS levels were detected when single mycotoxin was tested. Also, the results revealed a significant increase in GSH/GSSG ratio at all concentrations after 24 h. Expression levels of CASP3 and BAX were up regulated by α-ZEL while CASP3 and BCL2 were down regulated by ß-ZEL, revealing how ZEA´s metabolites can induce the expression of cell apoptosis genes. However, BEA down-regulated the expression of BCL2. Moreover, ß-ZEL + BEA was the only combination treatment which was able to down regulate the levels of cell apoptosis gene expression. Relying to our findings, α-ZEL, ß-ZEL and BEA, induce injury in SH-SY5Y cells elevating oxidative stress levels, disturbing the antioxidant activity role of glutathione system and finally, causing disorder in the expressions and activities of the related apoptotic cell death genes.


Assuntos
Depsipeptídeos/toxicidade , Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Zearalenona/toxicidade , Apoptose/efeitos dos fármacos , Apoptose/genética , Caspase 3/metabolismo , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Humanos , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima , Zearalenona/metabolismo , Zeranol/análogos & derivados , Zeranol/metabolismo , Zeranol/toxicidade
5.
PLoS One ; 15(9): e0239479, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32966310

RESUMO

Mycotoxin management in agriculture is an essential challenge for maintaining the health of both animals and humans. Choosing the right adsorbent is still a question for many breeders and an important criterion for feed manufacturers. New adsorbents are still being sought. Graphene oxide is a promising material in the field of nanotechnology, which excels in its adsorption properties. Presented in vitro study investigates graphene oxide for the binding of mycotoxins from crushed wheat. The results show that graphene oxide has an adsorption capacity for aflatoxin 0.045 mg/g, zearalenone 0.53 mg/g and deoxynivalenol 1.69 mg/g at 37° C. In vitro simulation of crushed wheat digestion showed rapid adsorption during the gastric phase. Of the minerals, Mg, Cu and Zn were the most adsorbed. The applied dose of graphene oxide of 10 mg/g caused only a slight inhibition of the digestive enzymes α-amylase and trypsin compared to pepsin and gastric lipase. In vitro results indicated the suitability of graphene oxide in the adsorption of the aflatoxin, zearalenone and deoxynivalenol.


Assuntos
Grafite/química , Micotoxinas/isolamento & purificação , Adsorção , Aflatoxina B1/isolamento & purificação , Aflatoxina B1/toxicidade , Ração Animal/análise , Ração Animal/toxicidade , Animais , Digestão , Contaminação de Alimentos/análise , Contaminação de Alimentos/prevenção & controle , Absorção Gastrointestinal , Humanos , Técnicas In Vitro , Micotoxinas/toxicidade , Nanoestruturas/química , Tricotecenos/isolamento & purificação , Tricotecenos/toxicidade , Triticum/química , Triticum/toxicidade , Zearalenona/isolamento & purificação , Zearalenona/toxicidade
6.
Ecotoxicol Environ Saf ; 204: 111072, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32758694

RESUMO

Zearalenone (ZEN) is a mycotoxin that causes serious health problems in humans and animals. However, few studies have focused on the destruction of the intestinal barrier caused by ZEN. In this study, rats were exposed to different dosages of ZEN (0, 0.2, 1.0 and 5.0 mg/kg bw) by gavage for 4 weeks. The results showed that 1.0 and 5.0 mg/kg ZEN impaired gut morphology, induced the inflammatory response, reduced mucin expression, increased intestinal permeability, decreased the expression of TJ proteins and activated the RhoA/ROCK pathway. However, 0.2 mg/kg ZEN had no significant effect on intestinal barrier except for reducing the expression of some TJ proteins and mucins. Moreover, exposure to ZEN led to slight imbalance in microbiota. In conclusion, ZEN exposure resulted in intestinal barrier dysfunction by inducing intestinal microbiota dysbiosis, decreasing the expression of TJ proteins, activating the RhoA/ROCK pathway, and inducing the inflammatory response.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Jejuno/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Relação Dose-Resposta a Droga , Disbiose/induzido quimicamente , Feminino , Microbioma Gastrointestinal/genética , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Jejuno/microbiologia , Jejuno/patologia , Masculino , Mucinas/metabolismo , Permeabilidade , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo
7.
Toxicol Lett ; 333: 159-169, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32783910

RESUMO

The intestinal epithelium is the first barrier against food contaminants and is highly sensitive to Fusarium toxins, especially deoxynivalenol (DON) and zearalenone (ZEA). Here, we explored the effects of low doses of DON and/or ZEA in naturally moldy diets on intestinal functions in piglets, including inflammatory responses, epithelial barrier, and microbial composition. Piglets were treated with a control diet (CON), DON diet (1000.6 µg/kg), ZEA diet (269.1 µg/kg), and DON + ZEA diet (1007.5 + 265.4 µg/kg), respectively, for 3 weeks and then switched to the same CON diet for another 2 weeks. In the first period, even the selected low doses of DON or ZEA in the diet resulted in intestinal inflammation, diminish protein expression (claudin-4) and altered gut microbiota populations. Whereas upon switching to the CON diet for another 2 weeks, the deleterious effect of ZEA and DON on IL-1ß and Bifidobacterium population could not be recovered. Additionally, combined DON and ZEA negatively affected body weight gain and feed consumption of piglets, as well as shown synergistic effects on evoking pro-inflammatory cytokines contents (TNF-α, IL-1ß, and IL-6) and perturbing the cecum microbiota profile (E. coli, Lactobacillus, and Bifidobacterium). Collectively, chronic consumption of DON and ZEA contaminated feed or food, even at low doses, can induce intestinal damage and may have consequences for animal and human health.


Assuntos
Ração Animal/microbiologia , Imunidade nas Mucosas/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Suínos , Tricotecenos/toxicidade , Zearalenona/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Ceco/efeitos dos fármacos , Ceco/imunologia , Ceco/metabolismo , Citocinas/sangue , Citocinas/genética , Citocinas/metabolismo , Dieta , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Feminino , Contaminação de Alimentos/análise , Fusarium/crescimento & desenvolvimento , Fusarium/isolamento & purificação , Expressão Gênica/efeitos dos fármacos , Hordeum/microbiologia , Inflamação , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Jejuno/efeitos dos fármacos , Jejuno/imunologia , Jejuno/metabolismo , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo , Zea mays/microbiologia
8.
Toxicon ; 185: 104-113, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32653416

RESUMO

Fungi produce mycotoxins in the presence of appropriate temperature, humidity, sufficient nutrients and if the density of the mushroom mass is favorable. Although all mycotoxins are of fungal origin, all toxic compounds produced by fungi are not called mycotoxins. The interest in mycotoxins first started in the 1960s, and today the interest in mycotoxin-induced diseases has increased. To date, 400 mycotoxins have been identified and the most important species producing mycotoxins belongs to Aspergillus, Penicillium, Alternaria and Fusarium genera. Mycotoxins are classified as hepatotoxins, nephrotoxins, neurotoxins, immunotoxins etc. In this review genotoxic and also other health effects of some major mycotoxin groups like Aflatoxins, Ochratoxins, Patulin, Fumonisins, Zearalenone, Trichothecenes and Ergot alkaloids were deeply analyzed.


Assuntos
Mutagênicos/toxicidade , Micotoxinas/toxicidade , Aflatoxinas/toxicidade , Aspergillus , Dano ao DNA , Contaminação de Alimentos , Microbiologia de Alimentos , Fumonisinas/toxicidade , Fungos , Fusarium , Ocratoxinas/análise , Patulina , Tricotecenos/toxicidade , Zearalenona/toxicidade
9.
Chemosphere ; 255: 126999, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32679628

RESUMO

Currently there are few reports on the combined immunotoxicity of zearaleone (ZEA) and deoxynivalenol (DON). Since the two coexist naturally, it is necessary to understand the immunotoxicity caused by the two mycotoxins alone and in combination. To examine T lymphocytes activation and immune effect during activation, we used mouse primary spleen T lymphocytes as the experimental material and concanavalin (Con A) as the stimulator. The effects of ZEA, DON, and their combined exposure on T lymphocytes immune related function and the relationship between the activation of the mitogen-activated protein kinase (MAPK) signaling pathway and mycotoxin induced T lymphocytes apoptosis were studied in vitro. Specifically, T lymphocytes were isolated from primary mouse splenic lymphocytes, activated by Con A and then exposed to different concentrations of ZEA, DON, and their combinations. Our results showed that ZEA and DON alone and their combinations (20:1) can decrease the cell viability of T lymphocytes activated by Con A. The inhibitory effect of the combined groups was greater than that of the single mycotoxins, showing a synergistic effect. In addition, single or combined mycotoxins can lead to intracellular and surface ultrastructure damage of T lymphocytes, inhibit the expression of CD25 and CD278 and inhibit the synthesis of effect molecules poreforming protein (PFP), granzyme A (GZMA), and tumor necrosis factor-α (TNF-α). Meanwhile, the single mycotoxin or combined mycotoxins can promote the apoptosis of T lymphocytes which was accompanied by the overactivation of MAPK. After using the inhibitors of extracellular regulated protein kinases (ERK) and c-Jun N-terminal kinase (JNK) in the MAPK pathway, we found that the apoptosis of the cells induced by the ZEA was significantly decreased, and the apoptosis of the cells induced by DON had no significant changes. This suggests that the activation of MAPK induced by ZEA can promote the apoptosis of T lymphocytes, but the activation of MAPK induced by DON is not directly related to T cell apoptosis.


Assuntos
Imunotoxinas/toxicidade , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Tricotecenos/toxicidade , Zearalenona/toxicidade , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Subunidade alfa de Receptor de Interleucina-2 , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos , Micotoxinas/toxicidade , Transdução de Sinais , Linfócitos T/imunologia , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa
10.
J Agric Food Chem ; 68(29): 7757-7764, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32584032

RESUMO

Juveniles are considered as one of the most vulnerable population groups concerning mycotoxins and their modified forms. The weaning stage is a particularly vulnerable period in the life of mammals, reflected in intestinal and immune dysfunction. The current study investigated the toxicokinetic (TK) characteristics of zearalenone (ZEN), zearalenone-14-glucoside (ZEN14G), and zearalenone-14-sulfate (ZEN14S) in weaned (4-week-old) piglets, by means of oral and intravenous administration of equimolar doses, i.e., 331, 500, and 415 µg/kg bodyweight, respectively. Plasma and urine were sampled pre- and post-administration and were quantitatively analyzed for ZEN, ZEN14G, ZEN14S, and in vivo metabolites by liquid chromatography-high-resolution mass spectrometry. Tailor-made TK models were elaborated to process data. A statistical comparison of the results was performed with TK data obtained in a previously reported study in pigs of 8 weeks of age. Additionally, porcine plasma protein binding was determined to support TK findings. The TK results for ZEN, ZEN14G, and ZEN14S, obtained in 4- and 8-week-old pigs, revealed significant age-related differences, based on differences in intestinal permeability, body fat content, gastrointestinal transit time, and biotransformation, with a special emphasis on an increased absorbed fraction of ZEN14G, i.e., 94 vs 61% in 4- compared to 8-week-old pigs. Since the growing pig has been reported to be a suitable pediatric animal model for humans concerning TK processes, these results may contribute to refine the risk assessment concerning modified ZEN forms in juvenile animals and humans.


Assuntos
Glucosídeos/farmacocinética , Suínos/sangue , Suínos/urina , Zearalenona/análogos & derivados , Zearalenona/farmacocinética , Fatores Etários , Animais , Feminino , Glucosídeos/sangue , Glucosídeos/toxicidade , Glucosídeos/urina , Masculino , Sulfatos/sangue , Sulfatos/toxicidade , Sulfatos/urina , Suínos/crescimento & desenvolvimento , Toxicocinética , Zearalenona/sangue , Zearalenona/toxicidade , Zearalenona/urina
11.
Ecotoxicol Environ Saf ; 194: 110420, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32151861

RESUMO

In order to alleviate toxic effects of aflatoxins B1 (AFB1) and zearalenone (ZEA) on broiler production performance and gut microbiota, three kinds of compound probiotics (CP) were selected. The optimal ratios of Bacillus subtilis, Lactobacillus casei and Candida utilis in broiler diets were 7, 5 and 6 log CFU/g for ZEA biodegradation (CP1); 6, 7 and 7 log CFU/g for AFB1 biodegradation (CP2); 7, 6 and 7 log CFU/g for ZEA + AFB1 biodegradation (CP3). A total of 350 1-day-old Ross broilers were randomly divided into 7 groups. Group A was the basal diet, group B-G contained ZEA, AFB1, ZEA + AFB1, ZEA + CP1, AFB1+CP2, ZEA + AFB1+CP3, respectively. The experiment showed that AFB1 or AFB1+ZEA significantly decreased broiler production performance, damaged liver and jejunum, increased mycotoxin residues in broiler body; however, three kinds of compound probiotics additions could alleviate mycotoxin negative effects on the above parameters (p < 0.05). The gut microbiota analysis indicated that AFB1+ZEA increased jejunal microbial richness, but which were decreased to almost the same level as the control group by CP3 addition. CP3 addition significantly increased jejunal Firmicutes and Lactobacillus aviarius abundances. The correlative analysis showed that gut Lactobacillus aviarius abundance was positively correlated with average daily gain (ADG) of broilers (p < 0.05), while AFB1+ZEA addition decreased its relative abundance, indicating that CP3 addition increased broiler growth by increasing Lactobacillus aviarius abundance. AFB1 and ZEA residues in broiler body were negatively correlated with the gut beneficial bacterial abundances (p < 0.01), but positively correlated with the potentially harmful bacterial abundances (p < 0.05), which inferred that CP3 addition could decrease mycotoxin residues through positively regulating gut relative bacterial abundances. In conclusion, compound probiotics could keep gut microbiota stable, degrade mycotoxins, alleviate histological lesions, increase production performance and reduce mycotoxin toxicity for broilers.


Assuntos
Aflatoxina B1/toxicidade , Galinhas/crescimento & desenvolvimento , Microbioma Gastrointestinal/efeitos dos fármacos , Probióticos/farmacologia , Zearalenona/toxicidade , Ração Animal/análise , Ração Animal/microbiologia , Animais , Bacillus subtilis/isolamento & purificação , Galinhas/metabolismo , Dieta , Suplementos Nutricionais , Firmicutes/isolamento & purificação , Distribuição Aleatória
12.
Toxicol Lett ; 326: 52-60, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32119988

RESUMO

Zearalenone, produced by various Fusarium species, is a non-steroidal estrogenic mycotoxin that contaminates cereals, resulting in adverse effects on human health. We investigated the effects of zearalenone and its metabolite alpha zearalenol on epigenetic modifications and its relationship with metabolic pathways in human hepatocellular carcinoma cells following 24 h of exposure. Zearalenone and alpha zearalenol at the concentrations of 1, 10 and 50 µM significantly increased global levels of DNA methylation and global histone modifications (H3K27me3, H3K9me3, H3K9ac). Expression levels of the chromatin modifying enzymes EHMT2, ESCO1, HAT1, KAT2B, PRMT6 and SETD8 were upregulated by 50 µM of zearalenone exposure using PCR arrays, consistent with the results of global histone modifications. Zearalenone and alpha zearalenol also changed expression levels of the AhR, LXRα, PPARα, PPARÉ£, L-fabp, LDLR, Glut2, Akt1 and HK2 genes, which are related to nuclear receptors and metabolic pathways. PPARÉ£, a key regulator of lipid metabolism, was selected from among these genes for further analysis. The PPARÉ£ promoter reduced methylation significantly following zearalenone exposure. Taken together, the epigenetic mechanisms of DNA methylation and histone modifications may be key mechanisms in zearalenone toxicity. Furthermore, effects of zearalenone in metabolic pathways could be mediated by epigenetic modifications.


Assuntos
Epigênese Genética/efeitos dos fármacos , Fusarium/química , Expressão Gênica/efeitos dos fármacos , Células Hep G2/efeitos dos fármacos , Micotoxinas/toxicidade , Zearalenona/toxicidade , Zeranol/análogos & derivados , Metilação de DNA/efeitos dos fármacos , Células Hep G2/metabolismo , Humanos , Zeranol/metabolismo , Zeranol/toxicidade
13.
Ecotoxicol Environ Saf ; 194: 110401, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32143102

RESUMO

Zearalenone (ZEA), a toxic substance produced by Fusarium fungi, accumulated in cereals grain and animal feed, causes injury to humans and animals. ZEA can induce obvious reproductive toxicity with the ovarian granulosa cells (GCs) as the main target. However, the study on exploring the protective compounds against ZEA-induced mouse primary ovarian GCs damage remains less. In the current study, the protective effect of 20 compounds derived from traditional Chinese medicines (TCMs) on the injury of mouse GCs caused by ZEA were evaluated using MTT assay and the cell morphology. Our results showed that chlorogenic acid (250, 500, and 1000 µg/mL) significantly suppress ZEA-induced GCs death. Western blot analysis suggested chlorogenic acid could rescue the up-regulated apoptosis of GCs induced by ZEA via attenuating the protein expression of cleaved caspase-3, the ratio of Bax/Bcl-2 and cleaved-PARP. Our results provide strong evidence that chlorogenic acid warrants further optimization for more potent and safer compounds for against the ZEA lead toxicity to humans and animals.


Assuntos
Apoptose/efeitos dos fármacos , Ácido Clorogênico/farmacologia , Células da Granulosa/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Caspase 3/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Células da Granulosa/metabolismo , Células da Granulosa/patologia , Camundongos , Camundongos Endogâmicos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
14.
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
15.
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
16.
Bioelectrochemistry ; 133: 107453, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31972449

RESUMO

Mycotoxin contamination in food and feed is a global concern because mycotoxin contamination can cause both acute and chronic health effects in humans and animals. In the present work, an Escherichia coli-based biosensor is described for the toxicity assessment of aflatoxin B1 (AFB1) and zearalenone (ZEN). In this electrochemical biosensor, E. coli is used as the signal recognition element, p-benzoquinone is used as the mediator, and a two-step reaction procedure has been developed to separate the mediator from the mycotoxins. The current value of the as-prepared microbial biosensor exhibits a linear decrease with concentrations of AFB1 and ZEN in the range of 0.01-0.3 and 0.05-0.5 µg/mL, with detection limits reaching 1 and 6 ng/mL, respectively. The IC25 values obtained by the present method are 0.25 and 0.40 µg/mL for AFB1 and ZEN, which shows that the cytotoxicity of AFB1 to E. coli is more severe than the cytotoxicity of ZEN to E. coli. The combined toxic effect of these two mycotoxins has also been explored, and synergistic biotoxicity has been observed. Moreover, the biosensor is successfully applied to the toxicity evaluation of mycotoxins in real samples, including peanut and corn oils. This work could provide new insight into mycotoxin and microorganism interactions and could establish a new approach for future mycotoxin detection.


Assuntos
Técnicas Biossensoriais/métodos , Escherichia coli/efeitos dos fármacos , Análise de Alimentos/métodos , Contaminação de Alimentos/análise , Micotoxinas/toxicidade , Aflatoxina B1/toxicidade , Escherichia coli/citologia , Testes de Toxicidade/métodos , Zearalenona/toxicidade
17.
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
18.
Toxicology ; 429: 152337, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31760079

RESUMO

Zearalenone (ZEA) contamination of feed affects animal husbandry and the human health. Currently, the molecular mechanism underlying small intestine-related diseases caused by ZEA-induced oxidative stress is not well understood. In this study, we aimed to identify the mechanisms involved in ZEA (0.5-1.5 mg/kg)-induced oxidative stress in the ileum and mesenteric lymph nodes (MLNs) and the role of the Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in post-weaning gilts. Forty post-weaning gilts (Landrace × Yorkshire × Duroc) with an average body weight of 14.01 ± 0.86 kg were randomly allocated to four groups and fed a corn-soybean meal basal diet supplemented with < 0.1, 0.5, 1.0, or 1.5 mg/kg ZEA. The results showed that the activity of total superoxide dismutase and glutathione peroxidase decreased (p < 0.05) linearly and quadratically and that the content of malondialdehyde increased (p < 0.05) quadratically in the ileum and MLNs with increasing ZEA in the diet. Immunohistochemical analysis showed that the expression of Nrf2 and glutathione peroxidase 1 (Gpx1) immunoreactive proteins in the ileum and MLNs were significantly enhanced with increasing ZEA. The relative mRNA and protein expression of Nrf2, Gpx1, quinone oxidoreductase 1 (Nqo1), hemeoxygenase 1 (Ho1), modifier subunit of glutamate-cysteine ligase (Gclm), and catalytic subunit of glutamate-cysteine ligase (Gclc) increased (p < 0.05) linearly and quadratically, and the relative mRNA and protein expression of Keap1 decreased (p < 0.05) linearly and quadratically in the ileum with increasing ZEA concentrations in the diet. Further, the relative mRNA and protein expression of Nrf2 and Gpx1 increased (p < 0.05) linearly and quadratically, and the relative mRNA and protein expression of Nqo1, Ho1, and Gclm decreased (p < 0.05) quadratically in the MLNs as ZEA concentrations increased in the diet. Our results provide valuable genetic information on ZEA-induced oxidative stress in the ileum and MLNs of post-weaning gilts and have elucidated the key regulatory genes involved in the Keap1-Nrf2 signaling pathway. Results indicated that the Keap1-Nrf2 signaling pathway might be a key target to further prevent and treat ZEA-induced injury to the ileum in post-weaning gilts.


Assuntos
Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Relação Dose-Resposta a Droga , Feminino , Íleo/metabolismo , Linfonodos/metabolismo , Mesentério/metabolismo , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Suínos , Desmame , Zearalenona/administração & dosagem
19.
Toxicon ; 173: 75-93, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31734251

RESUMO

Plant-based materials used in the production of pig feed are very often contaminated with deoxynivalenol and zearalenone. Daily intake of small amounts of these mycotoxins with feed induces various subclinical states in gilts and influences different biological processes. The aim of this preclinical study was to determine the correlation between monotonic doses of zearalenone and deoxynivalenol (40 µg/kg body weight and 12 µg/kg body weight, respectively, administered over a period of 42 days) and the immunohistochemical expression of estrogen receptors in the intestinal tract and the mRNA expression of selected colonic enzymes. The immunohistochemical expression of estrogen receptor alpha was observed in the colon, but its intensity varied in different weeks of exposure. A minor increase in estrogen receptor beta expression was noted only in the colon, whereas the expression of cytochrome P450 1A1 enzyme mRNA and mRNA isoform of the glutathione S-transferase π gene decreased. The observed correlations suggest that the risk of loss of control over the biotransformation and biological activity of the parent compounds in distal intestinal mucosa is delayed.


Assuntos
Estrogênios não Esteroides/toxicidade , Mucosa Intestinal/fisiologia , Venenos/toxicidade , Receptores Estrogênicos/metabolismo , Suínos/fisiologia , Tricotecenos/toxicidade , Zearalenona/toxicidade , Animais , Peso Corporal , Colo , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Feminino , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Intestinos , Micotoxinas , RNA Mensageiro/metabolismo , Sus scrofa
20.
Crit Rev Food Sci Nutr ; 60(16): 2710-2729, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31446772

RESUMO

Zearalenone (ZEA) is a mycotoxin produced by the fungi of Fusarium genera, which contaminates the cereals and food stuffs worldwide. Fusarium mycotoxins are considered as important metabolites related to animal and human health. Evidences indicate that ZEA has been found to be present in different food stuffs from developed countries like USA, Canada, France, Germany, Japan, etc. and developing nations like Egypt, Thailand, Iran, Croatia, Philippines, etc. The toxicokinetic studies reveal that following oral exposure of ZEA, the compound is absorbed through gastrointestinal tract (GIT), gets metabolized and distributed to different body parts. ZEA has been shown to cause reproductive disorders in laboratory animals. Although the toxicity of ZEA in humans have not been conclusively established nonetheless, limited evidences indicate that ZEA can cause hyper estrogenic syndrome. Though, ZEA causes low acute toxicity, but reports are available confirming the systemic toxicity caused by ZEA. There is no review available that addresses the occurrence, systemic toxicity and the probable mechanisms of ZEA toxicity. This review shall address the world-wide occurrence and in vivo & in vitro toxicity studies of ZEA over the past 20 years. The review shall also discuss the toxicokinetics of ZEA and metabolites; illustrates the systemic toxicity and probable mechanisms of action leading to the risk associated with ZEA.


Assuntos
Contaminação de Alimentos/análise , Fusarium/química , Micotoxinas/toxicidade , Zearalenona/toxicidade , Animais , Países Desenvolvidos , Países em Desenvolvimento , Humanos , Micotoxinas/metabolismo , Micotoxinas/farmacocinética , Zearalenona/metabolismo , Zearalenona/farmacocinética
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