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1.
Int J Mol Sci ; 23(20)2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36293400

RESUMO

Zearalenone (ZEN) is a widespread contaminant of cereals and agricultural products which causes food safety issues. Ingesting food or feed contaminated with ZEN can disrupt the intestinal epithelial barrier function. The RhoA/ROCK signaling pathway plays a key role in regulating the epithelial barrier function, but studies on such roles have rarely focused on the intestine. The aim of this experiment was to investigate the exact mechanism of ZEN-induced intestinal barrier damage and whether the RhoA/ROCK signaling pathway is involved. The results showed that ZEN significantly induced alkaline phosphatase (AP) activity and FITC-dextran (4 kDa) passage across the epithelial barrier, which significantly reduced the transepithelial resistance (TEER). Meanwhile, ZEN could induce the significantly down-regulated mRNA expression of tight junction proteins (occludin, claudin-1, ZO-1, and claudin-3) and redistribution of ZO-1 immunofluorescence. Further studies demonstrated that ZEN exposure activated the RhoA/ROCK signaling pathway, significantly up-regulated the mRNA expression of ROCK1, the main effector of the signaling pathway, the protein expression of phosphorylated myosin light chain (MLC) and myosin light chain kinase (MLCK), and relatively increased the activity of ATP in cells, simultaneously remodeling the cytoskeleton (F-actin). Overall, our study indicated that ZEN induced intestinal barrier dysfunction by activating the RhoA/ROCK signaling pathway.


Assuntos
Quinase de Cadeia Leve de Miosina , Zearalenona , Quinase de Cadeia Leve de Miosina/genética , Quinase de Cadeia Leve de Miosina/metabolismo , Cadeias Leves de Miosina/metabolismo , Zearalenona/metabolismo , Ocludina/metabolismo , Claudina-1/metabolismo , Actinas/metabolismo , Claudina-3/metabolismo , Fosfatase Alcalina/metabolismo , Mucosa Intestinal/metabolismo , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo , Intestinos , Transdução de Sinais , RNA Mensageiro/metabolismo , Trifosfato de Adenosina/metabolismo
2.
Toxins (Basel) ; 13(12)2021 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-34941728

RESUMO

Zearalenone (ZEN) is a non-steroidal estrogen mycotoxin produced by Fusarium fungi, which inevitably exists in human and animal food or feed. Previous studies indicated that apoptosis seems to be a key determinant of ZEN-induced toxicity. This experiment aimed to investigate the protective effects of Glutamine (Gln) on ZEN-induced cytotoxicity in IPEC-J2 cells. The experimental results showed that Gln was able to alleviate the decline of cell viability and reduce the production of reactive oxygen species and calcium (Ca2+) induced by ZEN. Meanwhile, the mRNA expression of antioxidant enzymes such as glutathione reductase, glutathione peroxidase, and catalase was up-regulated after Gln addition. Subsequently, Gln supplementation resulted in the nuclear fission and Bad-fluorescence distribution of apoptotic cells were weakened, and the mRNA expression and protein expression of pro-apoptotic genes and apoptotic rates were significantly reduced. Moreover, ZEN reduced the phosphorylation Akt, decreased the expression of Bcl-2, and increased the expression of Bax. Gln alleviated the above changes induced by ZEN and the antagonistic effects of Gln were disturbed by PI3K inhibitor (LY294002). To conclude, this study revealed that Gln exhibited significant protective effects on ZEN-induced apoptosis, and this effect may be attributed to the PI3K/Akt signaling pathway.


Assuntos
Apoptose/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Glutamina/metabolismo , Glutamina/farmacologia , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Zearalenona/toxicidade
3.
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
4.
Toxins (Basel) ; 10(10)2018 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-30304829

RESUMO

Zearalenone (ZEN), a nonsteroidal estrogen mycotoxin, is widely found in feed and foodstuffs. Intestinal cells may become the primary target of toxin attack after ingesting food containing ZEN. Porcine small intestinal epithelial (SIEC02) cells were selected to assess the effect of ZEN exposure on the intestine. Cells were exposed to ZEN (20 µg/mL) or pretreated with (81, 162, and 324 µg/mL) N-acetylcysteine (NAC) prior to ZEN treatment. Results indicated that the activities of glutathione peroxidase (Gpx) and glutathione reductase (GR) were reduced by ZEN, which induced reactive oxygen species (ROS) and malondialdehyde (MDA) production. Moreover, these activities increased apoptosis and mitochondrial membrane potential (ΔΨm), and regulated the messenger RNA (mRNA) expression of Bax, Bcl-2, caspase-3, caspase-9, and cytochrome c (cyto c). Additionally, NAC pretreatment reduced the oxidative damage and inhibited the apoptosis induced by ZEN. It can be concluded that ZEN-induced oxidative stress and damage may further induce mitochondrial apoptosis, and pretreatment of NAC can degrade this damage to some extent.


Assuntos
Acetilcisteína/farmacologia , Apoptose/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Zearalenona/toxicidade , Animais , Linhagem Celular , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Malondialdeído/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Suínos
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