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1.
Sci Total Environ ; 806(Pt 3): 151192, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34710421

RESUMO

Mycotoxin, as one of the most common pollutants in foodstuffs, poses great threat to food security and human health. Specifically, deoxynivalenol (DON) and zearalenone (ZEN)-two mycotoxin contaminants with considerable toxicity widely existing in food products-have aroused broad public concerns. Adding to this picture, modified forms of DON and ZEN, have emerged as another potential environmental and health threat, owing to their higher re-transformation rate into parent mycotoxins inducing accumulation of mycotoxin in humans and animals. Given this, a better understanding of the toxicity of modified mycotoxins is urgently needed. Moreover, the lack of toxicity data means a proper risk assessment of modified mycotoxins remains challenging. To better evaluate the toxicity of modified DON and ZEN, we have reviewed the relationship between their structures and toxicities. The toxicity mechanisms behind modified DON and ZEN have also been discussed; briefly, these involve acute, subacute, chronic, and combined toxicities. In addition, this review also addresses the global occurrence of modified DON and ZEN, and summarizes novel methods-including in silico analysis and implementation of relative potency factors-for risk assessment of modified DON and ZEN. Finally, the health risk assessment of modified DON and ZEN has also been discussed comprehensively.


Assuntos
Micotoxinas , Tricotecenos , Zearalenona , Animais , Contaminação de Alimentos/análise , Humanos , Micotoxinas/análise , Micotoxinas/toxicidade , Medição de Risco , Tricotecenos/toxicidade , Zearalenona/análise , Zearalenona/toxicidade
2.
Theriogenology ; 177: 22-28, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34656833

RESUMO

Zearalenone (ZEN) is one of the secondary metabolites of Fusarium and is regarded as a common contaminant of foodstuffs especially corn products. ZEN is considered to be cytotoxic, tissue toxic, genotoxic and reproductive toxic, which acts as a serious threat for humans and animals. In this study, we investigated the effects of ZEN on organelle function during porcine oocyte meiotic maturation. Our results showed that the expansion of cumulus granulosa cells and the extrusion of oocyte polar body were disturbed after ZEN exposure. Besides the aberrant mitochondrial distribution and impaired mitochondrial membrane potential after ZEN treatment during porcine oocyte maturation. We also found the fluorescence intensity of ER was decreased, and ZEN exposure altered ER stress level, showing with the reduced expression of GRP78. We also found that the spindle cortex distribution of Golgi apparatus was disrupted in ZEN-exposed oocytes, which was confirmed by the decreased level of GM130, moreover, our data also showed that Rab11-based vesical transport was disturbed, indicating the Golgi apparatus function was disrupted. Besides, the fluorescence intensity of lysosome was significantly increased, indicating the protein degradation and the potential autophagy occurrence after ZEN treatment. Thus, our results demonstrated that exposure to ZEN affected porcine oocyte meiotic maturation through its wide effects on organelle function for protein synthesis, transport and degradation.


Assuntos
Zearalenona , Animais , Células do Cúmulo , Feminino , Oócitos , Oogênese , Organelas , Suínos , Zearalenona/toxicidade
3.
Ecotoxicol Environ Saf ; 227: 112865, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34634598

RESUMO

Zearalenone(ZEA) is a kind of mycotoxin widely existing in nature, its toxic effects can lead to the reproductive disorders in humans and animals. The aim of this study was to investigate the mechanism of scutellarin against ovarian granulosa cell(GCs) injury induced by ZEA based on network pharmacology, molecular docking method. The results show that 293 drug targets of scutellarin were found from PhamMapper database, and 583 disease targets were selected from Genecards database. Finally, 57 scutellarin targets were obtained for the repair of GCs injury with gene intersection. The protein-protein interaction(PPI), gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) analysis indicated that MAPK signaling pathway was most likely activated by scutellarin. Scutellarin with JNK or Caspase-3 had minimal and negative free binding energy in molecular docking analysis, indicating that they might be the acting targets of scutellarin. Cell viability was significantly decreased in ZEA treated cells. However, GCs viability, the level of estradiol(E2) and progesterone(P4) were significantly increased with addition of scutellarin to ZEA treated cells. Western blot analysis showed that scutellarin significantly reduced the expression of JNK, c-jun and Cleaved-caspasee-3 in GCs compared with ZEA treatment. In conclusion, scutellarin could alleviate the ovarian GCs injury by down-regulating the expression of JNK, c-jun and Cleaved-caspase-3 through the activation of MAPK/JNK signaling pathway. Our results will provide a theoretical foundation for the treatment of reproductive disorders with scutellarin.


Assuntos
Zearalenona , Animais , Apigenina/farmacologia , Feminino , Glucuronatos , Células da Granulosa , Humanos , Simulação de Acoplamento Molecular , Zearalenona/toxicidade
4.
J Agric Food Chem ; 69(40): 12030-12038, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34586801

RESUMO

The contamination of mycotoxin zearalenone (ZEN) in foods has been reported worldwide, resulting in potential risks to food safety. However, the toxic mechanism of ZEN on neurodegenerative diseases has not been fully elucidated. Therefore, this study conducted in vivo ZEN neurotoxicity assessment on Parkinson's disease (PD)-related dopaminergic neurodegeneration and mitochondrial dysfunction using Caenorhabditis elegans. The results demonstrated that dopaminergic neuron damage was induced by ZEN exposure (1.25, 10, and 50 µM), and dopaminergic neuron-related behaviors were adversely affected subsequently. Additionally, the mitochondrial fragmentation was significantly increased by ZEN exposure. Moreover, upregulated expression of mitochondrial fission and cell apoptosis-related genes (drp-1, egl-1, ced-4, and ced-3) revealed the crucial role of DRP-1 on ZEN-induced neurotoxicity, which was further confirmed by drp-1 mutant and RNAi assays. In conclusion, our study indicates ZEN-induced dopaminergic neurodegeneration via DRP-1-involved mitochondrial fragmentation and apoptosis, which might cause harmful effects on PD-related symptoms.


Assuntos
Proteínas de Caenorhabditis elegans , Doença de Parkinson , Zearalenona , Animais , Apoptose , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Neurônios Dopaminérgicos , Mitocôndrias/genética , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Zearalenona/metabolismo , Zearalenona/toxicidade
5.
Ecotoxicol Environ Saf ; 225: 112786, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34555717

RESUMO

The occurrence of immuno-compromised status in animals with zearalenone (ZEA) exposure may be a critical contributor to associated mucosal (gastrointestinal tract) diseases. However, it is difficult to assess the associated risks with limited reference data. This study comprehensively discussed the effects of ZEA on intestinal immune components, cytokines and molecular mechanism of juvenile grass carp infected with Aeromonas hydrophila. Specifically, the fish were fed six graded levels of dietary ZEA (0-2507 µg kg-1 diet) for 70 d. The results pointed out that the average residual amount of ZEA in the intestines increased with dose level after ZEA feeding. We further performed an infection assay using A. hydrophila. After 14 d, ZEA groups increased enteritis morbidity rate compared with controls. The acid phosphatase (ACP), lysozyme (LZ) activities and immunoglobulin M (IgM) content were significantly decreased in three intestinal segments. Furthermore, ZEA could reduce the transcription of ß-defensin-1, Hepcidin, liver expressed antimicrobial peptide 2A/2B (LEAP-2A/2B) and Mucin-2. We next confirmed the loss of these immune components accompanied by the invasion of the intestinal barrier by bacteria, as indicated by activation of the nuclear factor κB (NF-κB) and the expression of downstream cytokines. Notably, the phosphorylated target of rapamycin (TOR) plays an important role in regulating these genes, thus indicating a possible target caused by ZEA. In summary, the extensive inhibition of immune components by ZEA promotes the spread of pathogens, which may increase the possibility of intestinal mucosa exposure and the risk of transforming disease.


Assuntos
Carpas , Zearalenona , Aeromonas hydrophila , Animais , NF-kappa B/genética , Sirolimo , Zearalenona/toxicidade
6.
Toxicon ; 202: 115-122, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34562499

RESUMO

Fusarium graminearum invasion and Zearalenone (ZEN)-mycotoxin contamination are considered the most global threat to food and feed. This study investigates the effect Lactobacillus plantarum MON03 viable cells (LPVC) and LP free cells supernatant (LPFCS) against Fusarium graminearum growth and ZEN production in vitro and evaluates if treatment with LP viable cells can counteract the negative effect of ZEN on inflammation and oxidative stress in mesenteric lymph nodes and serum biochemical parameters in mice. For the in vitro study, 7 days of LPVC, LPFCS and F. graminearum co-incubation at different concentrations was done in order to determine the antifungal activity and ZEN- production inhibition. Regarding the in vivo study, Balb/c mice were treated as following: Control, ZEN group, LP group and ZEN + LP group for 30 days. In vitro, LPVC showed an excellent antifungal activity after 7 days of co-incubation (103 CFU/ml). LPVC was succeeded also to inhibit ZEN production by the fungi. In vivo, ZEN has shown an important oxidative damage. As a result of the exposure to ZEN, an increase cytokines, as effectors of an inflammatory response, were observed in the mesenteric lymph nodes (MLN) of intoxicated mice. In parallel, a serum biochemical change was also observed. LPVC induced a reduction of ZEN-induced oxidative stress and counteracts also the biochemical parameters damage and the inflammatory markers increased by ZEN. LPVC can be valorized as an anti-cating agent in the vitro and in the gastro-intestinal tract to decrease ZEN-toxic effects.


Assuntos
Fusarium , Lactobacillales , Zearalenona , Animais , Suplementos Nutricionais , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Camundongos , Estresse Oxidativo , Zearalenona/análise , Zearalenona/toxicidade
7.
Ecotoxicol Environ Saf ; 225: 112737, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34482067

RESUMO

Zearalenone (ZEA) has an estrogenic effect and often causes reproductive damage. Pigs are particularly sensitive to it. Lycopene (LYC) is a type of fat-soluble natural carotenoid that has antioxidant, anti-inflammatory, anti-cancer, anti-cardiovascular and detoxifying effects. In this study, piglet sertoli cells (SCs) were used as research objects to investigate the mechanism of ZEA induced damage to piglet SCs and to evaluate the protective effect of LYC on ZEA induced toxic damage to piglet SCs. The results showed that ZEA damaged the cell structure and inhibited the expression of nuclear factor erythroid-2 related factor 2 (Nrf2) in the nucleus, which down-regulated the relative mRNA expression of heme oxygenase 1 (HO-1) and glutathione peroxidase 1 (GPX1) and decreased the activity of HO-1, glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD), resulting in an increase in malondialdehyde (MDA) and reactive oxygen species (ROS) content. ZEA downregulated the relative mRNA and protein expression of bcl-2 in piglet SCs, promoted cell apoptosis, and upregulated the relative mRNA and protein expression of LC3, beclin-1, and bax. After 3 h LYC-pretreatment, ZEA was added for mixed culture. The results of pretreatment with LYC showed that LYC could alleviate the cytotoxicity of ZEA to porlets SCs. Compared with ZEA group, improved the cell survival rate, promoted the expression of Nrf2 in the nucleus, upregulated the relative mRNA expression of HO-1 and GPX1, increased the activity of antioxidant enzymes, and reduced the levels of MDA and ROS. Moreover, after pretreatment with LYC, the mRNA expression of bcl-2 was upregulated, the apoptosis rate was decreased, the relative mRNA and protein expressions of LC3, beclin-1 and bax were downregulated, and autophagy was alleviated. In conclusion, LYC alleviated the oxidative damage of SCs caused by ZEA by promoting the expression of Nrf2 pathway and decreased autophagy and apoptosis.


Assuntos
Fator 2 Relacionado a NF-E2 , Zearalenona , Animais , Licopeno , Masculino , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Células de Sertoli/metabolismo , Transdução de Sinais , Suínos , Zearalenona/toxicidade
8.
Theriogenology ; 174: 124-130, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34428678

RESUMO

The aim of this study was to evaluate the effect of 1 µmol/L zearalenone (ZEN) and 1 µmol/L enterolactone (ENL), alone or in combination, on the survival and morphology of in vitro cultured ovarian preantral follicles. Ovaries from 10 sheep were collected at a local abattoir and fragmented, and the ovarian pieces were submitted to in vitro culture for 3 days in the presence or absence of the test compounds. The morphology of primordial and primary follicles was impaired by ZEN, whereas that of cultured secondary follicles was improved by ENL. However, the combination of ENL with ZEN impaired the quality of primary and secondary follicles. Both ZEN and ENL induced apoptosis, but only ZEN was responsible for oocyte autophagy. None of these xenoestrogens affected endoplasmic reticulum stress as observed by the unaltered expression of ERP29. Differently from ZEN, ENL increased the expression of the efflux transporter ABCG2. In conclusion, although ENL can counteract the negative effects of ZEN on primordial and primary follicles, this positive effect is not similar to that observed in ovarian tissue cultures in the presence of ENL alone.


Assuntos
Zearalenona , 4-Butirolactona/análogos & derivados , Animais , Feminino , Lignanas , Oócitos , Folículo Ovariano , Ovário , Ovinos , Zearalenona/toxicidade
9.
Cells ; 10(8)2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34440667

RESUMO

(1) Background: Deoxynivalenol (DON) and zearalenone (ZEA) are type B trichothecene mycotoxins that exert serious toxic effects on the reproduction of domestic animals. However, there is little information about the toxicity of mycotoxins on testis development in Equus asinus. This study investigated the biological effects of DON and ZEA exposure on Sertoli cells (SCs) of Equus asinus; (2) Methods: We administered 10 µM and 30 µM DON and ZEA to cells cultured in vitro; (3) Results: The results showed that 10 µM DON exposure remarkably changed pyroptosis-associated genes and that 30 µM ZEA exposure changed inflammation-associated genes in SCs. The mRNA expression of cancer-promoting genes was remarkably upregulated in the cells exposed to DON or 30 µM ZEA; in particular, DON and ZEA remarkably disturbed the expression of androgen and oestrogen secretion-related genes. Furthermore, quantitative RT-PCR, Western blot, and immunofluorescence analyses verified the different expression patterns of related genes in DON- and ZEA-exposed SCs; (4) Conclusions: Collectively, these results illustrated the impact of exposure to different toxins and concrete toxicity on the mRNA expression of SCs from Equus asinus in vitro.


Assuntos
Células de Sertoli/efeitos dos fármacos , Transcriptoma , Tricotecenos/toxicidade , Zearalenona/toxicidade , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Equidae , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células de Sertoli/metabolismo , Células de Sertoli/ultraestrutura
10.
Ecotoxicol Environ Saf ; 222: 112533, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34303040

RESUMO

The natural co-occurrence of multiple mycotoxins has been reported in cereals and cereal products worldwide. Even though the dietary exposure to mycotoxins constitutes a serious human health, most reports are limited to the toxic effect of individual mycotoxins. The purpose of the present study was to assess the combined toxic effects of zearalenone (ZEN) and fumonisin B1 (FB1) and the potential interaction of their mixture on zebrafish (Danio rerio) embryos. Our results showed that ZEN possessed the higher toxicity to embryonic zebrafish (7-day LC50 value of 0.78 mg a.i. L-1) compared with FB1 (7-day LC50 value of 227.7 mg a.i. L-1). The combination of ZEN and FB1 exerted an additive effect on zebrafish embryos. Meanwhile, the activities of antioxidant CAT, caspase-3, and detoxification enzyme CYP450, as well as the expressions of six genes (Mn-sod, cas9, bax, cc-chem, ERα, and crh) associated with oxidative stress, cellular apoptosis, immune system, and endocrine system were prominently altered in the mixture exposure compared with the corresponding single treatment group of ZEN or FB1. Taken together, the regulatory standards of mycotoxins in food and feed should be updated based on the mixture effects of mycotoxins, and there is an increased need on effective detoxification methods for controlling and reducing the toxicity of multiple mycotoxins in animal feed and throughout the food supply chain.


Assuntos
Fumonisinas , Zearalenona , Animais , Fumonisinas/toxicidade , Expressão Gênica , Humanos , Zearalenona/toxicidade , Peixe-Zebra/genética
11.
Artigo em Inglês | MEDLINE | ID: mdl-34266625

RESUMO

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


Assuntos
Micotoxinas/toxicidade , Oryza/toxicidade , Animais , Ensaio Cometa/métodos , Dano ao DNA/efeitos dos fármacos , Fumonisinas/toxicidade , Masculino , Ratos , Ratos Sprague-Dawley , Tricotecenos/toxicidade , Zearalenona/toxicidade
12.
Int J Mol Sci ; 22(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208060

RESUMO

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


Assuntos
Estrogênios/toxicidade , Genisteína/toxicidade , Lactonas/toxicidade , Zearalenona/metabolismo , Zearalenona/toxicidade , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Genisteína/química , Células HeLa , Humanos , Lactonas/química , Micotoxinas/toxicidade , Oxirredução , Zearalenona/química
13.
Sci Total Environ ; 788: 147792, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34134368

RESUMO

Zearalenone (ZEN) is a secondary metabolite, which is mainly produced by Fusarium fungi and exists in various feeds and agricultural products. Recently, an increasing amount of data has shown that ZEN, as an estrogen-like hormone, can have harmful effects on the female reproductive system, especially on oogenesis and folliculogenesis. Breast milk is considered to be the ideal form of nutrition for infants; however, there are some records of contaminants in food, such as mycotoxins, which may be transferred from maternal blood to milk. In this study, we investigated the toxic effects of breast milk on folliculogenesis in offspring following maternal ZEN exposure. Our results showed that maternal ZEN exposure significantly inhibited the process of primordial follicle (PF) assembly and reduced the number of PFs in suckled offspring's ovaries. In addition, RNA-seq analysis showed that RIG-I-like receptor (RLRs) signaling pathways were activated after exposed to ZEN, which increased the expression levels of DNA damage (γ-H2AX, RAD51, and PARP1) and apoptosis related protein (BAX/BCL2 and Caspase-3). Finally, ZEN exposure interfered with follicular development, as evidenced by the reduced percentages of oocyte maturation and embryonic development when the offspring grew to adolescence. It is worth noting that maternal ZEN exposure disrupted the tri-methylation levels of H3K4, H3K9, and H3K27 in the offspring's oocytes. Our results indicated that maternal ZEN exposure affected ovarian development in offspring through the breast milk, which may be detrimental to their reproductive capability in adult life.


Assuntos
Zearalenona , Feminino , Humanos , Exposição Materna , Folículo Ovariano , Ovário , Gravidez , Reprodução , Zearalenona/toxicidade
14.
Ecotoxicol Environ Saf ; 221: 112457, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34175827

RESUMO

Zearalenone (ZEA) is an oestrogen-like mycotoxin produced by Fusarium fungi, which has a considerable impact on human and animal health and results in substantial economic losses worldwide. This study aimed to demonstrate the reproductive injury induced by ZEA in rodents. We conducted a rigorous meta-analysis of the related literature via PubMed, Embase, and Web of Science. The scope of the study includes the following: development of reproductive organs, serum testosterone, oestradiol, and luteinizing hormone (LH) levels; parameters of Leydig cells; and parameters of semen. In total, 19 articles were reviewed. Compared with the control group, the increased relative epididymis weight, increased serum oestradiol level, and decreased LH levels in the prenatally exposed group were observed. In pubertal and adult rodents, the relative testicular weight, serum oestradiol level, Leydig cell number, and percentage of ST (+) Leydig cells decreased under ZEA exposure. In rodents at all ages, decreased serum testosterone level, sperm concentration, sperm motility rate, and increased serum deformity rate were observed in exposed groups compared with control groups. Although subgroup analysis failed to identify a clear dose-response relationship between ZEA exposure and reproductive system damage in male rodents, we still managed to confirm that zearalenone could decrease the serum testosterone level at the dosage of 50 mg/kg*day, 1.4 mg/kg*day, and 84 mg/kg*day, of prenatal, pubertal, and mature rodents respectively; pubertal zearalenone exposure impairs the quality and quantity of sperms of rodents at the dosage of 1.4 mg/kg*day and mature zearalenone exposure has the same effect at the dosage of 84 mg/kg*day. In conclusion, we found that ZEA exposure can cause considerable damage to the reproductive system of rodents of all ages. While the exact underlying mechanism of ZEA-induced toxicity in the reproductive system remains largely unknown, the theories of oestrogen-like effects and oxidative stress damage are promising.


Assuntos
Estrogênios/toxicidade , Reprodução/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Masculino
15.
Environ Sci Pollut Res Int ; 28(42): 60276-60289, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34156614

RESUMO

Zearalenone (ZEA) and Deoxynivalenol (DON) are two mycotoxins highly detected in agricultural products and feed. Both mycotoxins produce reproductive toxicity and pose a serious threat to human and animal health, among which pigs are the most sensitive animals. Sertoli cells (SCs) play an important role in spermatogenesis; however, the combined toxicity of ZEA and DON and the screening of effective protective agents remains to be determined. By studying the effects of N-acetylcysteine (NAC) on the cells exposed to 20 µM of ZEA and 0.6 µM of DON, we explored the protective mechanism of NAC (4 mM) on the cytotoxic injury of piglets SCs induced by both mycotoxins. The results showed that the combination of ZEA and DON destroy organelles and SCs structures, NAC significantly alleviates the damage caused by ZEA and DON. NAC also significantly increased the expression and distribution of zonula occludens 1 (ZO-1), decreased the relative mRNA and protein expression levels of Bax, Bid, caspase-3, and caspase-9, and increased Bcl-2 expression level and inhibited the decrease of mitochondrial membrane potential. Further, NAC also eases the cell cycle arrest and oxidative stress caused by ZEA and DON. In summary, our results show that NAC could alleviate SCs injury via reducing the oxidative damage and apoptosis caused by ZEA and DON.


Assuntos
Tricotecenos , Zearalenona , Acetilcisteína/farmacologia , Animais , Masculino , Células de Sertoli , Suínos , Tricotecenos/toxicidade , Zearalenona/toxicidade
16.
Environ Pollut ; 287: 117557, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34167001

RESUMO

Zearalenone (ZEA) is an estrogenic toxin produced by Fusarium strains, that is widely present in crops, and endangers the reproductive system of animals. Tannic acid (TA) is a natural polyphenolic substance that is widespread in the roots, stems, and leaves of plants, and has special pharmacological activity. This study was designed to investigate the therapeutic effect of TA on ZEA-induced ovarian damage in mice and to explore the molecular mechanism involved. Ninety healthy Kunming female mice were divided into six equal groups. All the groups but the control group were administered daily with ZEA [10 mg/kg body weight (bw)] orally, for 7 days, to induce damage to the reproductive system. Some groups were also administered with TA (50, 100, and 200 mg/bw) for 7 days. Mice were euthanized 24 h later to allow for collection of serum and ovaries. TA can effectively alleviate the appearance of congestion and redness of the ovary, caused by ZEA, and increase the number of healthy growing follicles. Moreover, the estrogen content and the levels of MDA and ROS in the ovaries can be effectively reduced by TA. It can also reduce the apoptosis of ovarian cells, decreases the protein expression of the estrogen receptor, Fas, Fasl, caspase-3, caspase-8, caspase-9, and Bax, and increases the protein expression of Bcl-2. Our study indicates that TA reduces the strong estrogen and oxidative damage induced by ZEA, and these therapeutic effects may be partially mediated by the death receptor and mitochondrial apoptosis signaling pathway.


Assuntos
Zearalenona , Animais , Apoptose , Feminino , Camundongos , Receptores de Morte Celular , Transdução de Sinais , Taninos , Zearalenona/toxicidade
17.
Toxins (Basel) ; 13(6)2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073248

RESUMO

Plant materials can be contaminated with Fusarium mycotoxins and their derivatives, whose toxic effects on humans and animals may remain subclinical. Zearalenone (ZEN), a low-molecular-weight compound, is produced by molds in crop plants as a secondary metabolite. The objective of this study will be to analyze the in vivo correlations between very low monotonic doses of ZEN (5, 10, and 15 µg ZEN/kg body weight-BW for 42 days) and the carryover of this mycotoxin and its selected metabolites from the intestinal contents to the intestinal walls, the mRNA expression of estrogen receptor alfa (ERα) and estrogen receptor beta (ERß) genes, and the mRNA expression of genes modulating selected colon enzymes (CYP1A1 and GSTP1) in the intestinal mucosa of pre-pubertal gilts. An in vivo experiment will be performed on 60 clinically healthy animals with initial BW of 14.5 ± 2 kg. The gilts will be randomly divided into a control group (group C, n = 15) and three experimental groups (group ZEN5, group ZEN10, and group ZEN15; n = 15). Group ZEN5 will be administered per os 5 µg ZEN/kg BW (MABEL), group ZEN10-10 µg ZEN/kg BW (NOAEL), and group ZEN15-15 µg ZEN/kg BW (low LOAEL). In each group, five animals will be euthanized on analytical dates 1 (exposure day 7), 2 (exposure day 21), and 3 (exposure day 42). Samples for in vitro analyses will be collected from an intestinal segment resected from the following regions: the third (horizontal) part of the duodenum, jejunum, ileum, cecum, ascending colon, transverse colon, and descending colon. The experimental material will be collected under special conditions, and it will be transported to specialist laboratories where samples will be obtained for further analyses.


Assuntos
Mucosa Intestinal/efeitos dos fármacos , Receptores de Estrogênio/genética , Zearalenona/toxicidade , Animais , Citocromo P-450 CYP1A1/genética , Feminino , Glutationa Transferase/genética , Mucosa Intestinal/metabolismo , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real , Suínos
18.
Toxins (Basel) ; 13(6)2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34073731

RESUMO

Contamination of the world's food supply and animal feed with mycotoxins is a growing concern as global temperatures rise and promote the growth of fungus. Zearalenone (ZEN), an estrogenic mycotoxin produced by Fusarium fungi, is a common contaminant of cereal grains and has also been detected at lower levels in meat, milk, and spices. ZEN's synthetic derivative, zeranol, is used as a growth promoter in United States (US) and Canadian beef production. Experimental research suggests that ZEN and zeranol disrupt the endocrine and reproductive systems, leading to infertility, polycystic ovarian syndrome-like phenotypes, pregnancy loss, and low birth weight. With widespread human dietary exposure and growing experimental evidence of endocrine-disrupting properties, a comprehensive review of the impact of ZEN, zeranol, and their metabolites on the female reproductive system is warranted. The objective of this systematic review was to summarize the in vitro, in vivo, and epidemiological literature and evaluate the potential impact of ZEN, zeranol, and their metabolites (commonly referred to as mycoestrogens) on female reproductive outcomes. We conducted a systematic review (PROSPERO registration CRD42020166469) of the literature (2000-2020) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The data sources were primary literature published in English obtained from searching PubMed, Web of Science, and Scopus. The ToxR tool was applied to assess risk of bias. In vitro and in vivo studies (n = 104) were identified and, overall, evidence consistently supported adverse effects of mycoestrogens on physiological processes, organs, and tissues associated with female reproduction. In non-pregnant animals, mycoestrogens alter follicular profiles in the ovary, disrupt estrus cycling, and increase myometrium thickness. Furthermore, during pregnancy, mycoestrogen exposure contributes to placental hemorrhage, stillbirth, and impaired fetal growth. No epidemiological studies fitting the inclusion criteria were identified.


Assuntos
Estrogênios não Esteroides/toxicidade , Reprodução/efeitos dos fármacos , Zearalenona/toxicidade , Zeranol/toxicidade , Animais , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Placenta/efeitos dos fármacos , Gravidez , Útero/efeitos dos fármacos , Útero/patologia
19.
Ecotoxicol Environ Saf ; 220: 112367, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34052758

RESUMO

Zearalenone, which is ubiquitous in grains and animal feed, is a mycotoxin that can cause serious damage to animals and humans. Sertoli cells (SCs) can be used to study ZEA male reproductive toxicity in vitro. SCs provide energy for germ cells, where AMPK regulates intracellular energy. In order to explore the regulatory effect of AMPK on ZEA-induced lactate decline, we activated AMPK by AICAR and then inhibited AMPK by Compound C with ZEA-treated SCs for 24 h to detect intracellular lactate production-related indicators. Cell viability in the presence of 20 µmol/L ZEA and either 50 µmol/L AICAR or 5 µmol/L Compound C, respectively, did not damage SCs, and could effectively either activate or inhibit AMPK. Inhibition of AMPK promoted the production of pyruvate and lactate via increased expression of the glycolysis-related genes Pgam1 and the lactate production-related proteins GLUT1, LDHA, and MCT4. Activating AMPK inhibited the production of lactate and pyruvate by suppressing the expression of glycolysis-related genes HK1, Pgam1, and Gpi1 and that of lactate production-related proteins LDHA and MCT4. Zearalenone destroys the energy balance in SCs, activates P-AMPK, which inhibit the production of lactate and pyruvate in SCs. This also leads to the decrease of energy supply of SCs to spermatogenic cells, damages to reproductive system.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Estrogênios não Esteroides/toxicidade , Ácido Láctico/metabolismo , Células de Sertoli/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Metabolismo Energético/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Glicólise/genética , Masculino , Ácido Pirúvico/metabolismo , Ratos , Células de Sertoli/metabolismo
20.
Res Vet Sci ; 137: 48-55, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33932823

RESUMO

Zearalenone (ZEN), a nonsteroidal estrogenic mycotoxin, has a negative effect on porcine intestine. Glutamine (Gln) and alanyl-glutamine (Ala-Gln) are nutrients with potential preservation functions similar to those of the intestinal epithelial barrier. The protective role of Gln and Ala-Gln on ZEN-induced intestinal barrier dysfunction was evaluated in this study. Additionally, the ability of Gln and Ala-Gln to protect the intestinal barrier was investigated. Our results showed that lactate dehydrogenase (LDH) activity, paracellular permeability and reactive oxygen species (ROS) level were increased by ZEN, while the glutathione (GSH) level was decreased by ZEN. Gln and Ala-Gln promoted the proliferation of cells and attenuated the ZEN-induced increase in cytotoxicity, cell apoptosis and paracellular permeability. Gln and Ala-Gln alleviated barrier function damage, which was additionally induced by ZEN by increasing the antioxidant capacity of cells. In addition, Gln and Ala-Gln upregulated intestinal barrier associated gene expressions including pBD-1, pBD-2, MUC-2, ZO-1, occludin and claudin-3. This study revealed that Gln and Ala-Gln had similar effects in protecting intestinal epithelial barrier function against ZEN exposure in IPEC-J2 cells. A new treatment for alleviating ZEN-induced injury to the intestine through nutritional intervention is provided.


Assuntos
Dipeptídeos/farmacologia , Células Epiteliais/efeitos dos fármacos , Glutamina/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Células Epiteliais/metabolismo , Estrogênios não Esteroides , Enteropatias/veterinária , Mucosa Intestinal/metabolismo , Permeabilidade , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/metabolismo
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