Dataset Information

DL-Selenomethionine Alleviates Oxidative Stress Induced by Zearalenone via Nrf2/Keap1 Signaling Pathway in IPEC-J2 Cells.

ABSTRACT: Zearalenone (ZEN) is a kind of nonsteroidal mycotoxin that is considered a risk affecting the safety of human food and livestock feed that causes oxidative damages in mammalian cells. Selenomethionine (SeMet) was indicated to have antioxidant activity and received great interest in investigating the role of SeMet as a therapeutic agent in oxidation. Therefore, the aim of this study was to investigate the hormetic role of DL-SeMet in porcine intestinal epithelial J2 (IPEC-J2) cells against ZEN-induced oxidative stress injury. As a result of this experiment, 30 μg/mL of ZEN was observed with significantly statistical effects in cell viability. Following the dose-dependent manner, 20 μg/mL was chosen for the subsequent experiments. Then, further results in the current study showed that the ZENinduced oxidative stress with subsequent suppression of the expression of antioxidant stress pathway-related genes species. Moreover, SeMet reversed the oxidative damage and cell death of ZEN toxins to some extent, by a Nrf2/Keap1-ARE pathway. The finding of this experiment provided a foundation for further research on the ZEN-caused cell oxidative damage and the cure technology.

SUBMITTER: Sun H

PROVIDER: S-EPMC8402336 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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DL-Selenomethionine Alleviates Oxidative Stress Induced by Zearalenone via Nrf2/Keap1 Signaling Pathway in IPEC-J2 Cells.

Sun Haoyang H Zhang Meiling M Li Jianping J Shan Anshan A

Toxins 20210810 8

Zearalenone (ZEN) is a kind of nonsteroidal mycotoxin that is considered a risk affecting the safety of human food and livestock feed that causes oxidative damages in mammalian cells. Selenomethionine (SeMet) was indicated to have antioxidant activity and received great interest in investigating the role of SeMet as a therapeutic agent in oxidation. Therefore, the aim of this study was to investigate the hormetic role of DL-SeMet in porcine intestinal epithelial J2 (IPEC-J2) cells against ZEN-in ...[more]

PMID: 34437428

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Project description:Introduction: This study aimed to assess the alleviative effect of quercetagetin (QG) on zearalenone (ZEN)-induced liver injury in rabbits. Methods: Ninety 41-day-old healthy Hyla rabbits were randomly assigned into three groups, including a control (fed with basic diet), ZEN addition group (fed with basic diet + 600 μg/kg ZEN), and ZEN + QG addition group (fed with basic diet + 600 μg/kg ZEN + 100 mg/kg QG), with 30 rabbits per group. The duration of the experiment was 28 days. Results: The results revealed no significant differences in the average daily gain, average daily feed intake, the gain to feed ratio and the liver, kidney and spleen organ indexes (p > 0.05) between the rabbits across the three groups. However, the sacculus rotundus index of the rabbits in the control group was significantly higher than that in the ZEN + QG group (p < 0.05). The intake of ZEN-contaminated diet also significantly increased the activities or levels of alanine transaminase, alkaline phosphatase, total bile acid (TBA), total bilirubin, malondialdehyde, and interleukin-4 (IL-4) and enhanced the abundance of kelch-like ECH-associated protein 1 (Keap1), heat shock protein 70 (HSP70) and cysteine-aspartic acid protease-3 (Caspase-3) mRNA in the blood or liver tissue in ZEN group, compared to the control group (p < 0.05). On the contrary, the activities or levels of immunoglobulin A, complement 3, total antioxidant capacity, glutathione peroxidase (GSH-Px), superoxide dismutase, interleukin-10, and the abundance of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) mRNA were significantly decreased (p < 0.05). Supplementing the diet with QG still maintained significantly higher levels of TBA and IL-4, and the abundance of GSH-Px, HSP70, IL-4, and Caspase-3 mRNA in the blood and liver of rabbits in the ZEN + QG group than in the control group (p < 0.05). At the same time, the other indicators were restored to levels in the control group (p > 0.05). Discussion: In conclusion, QG alleviated the ZEN-induced oxidative damage and liver injury caused by inflammatory reaction through the Keap1-Nrf2-antioxidant response element (ARE) signal pathway, which protected the liver. This study revealed the alleviative effect of QG on the hepatotoxicity of ZEN in rabbits for the first time, providing a new perspective for applying QG and developing a ZEN antidote.

Project description:Zearalenone (ZEA) is a mycotoxin with an estrogen-like effect that is widely found in feed. Lipopolysaccharides (LPS) derived from Gram-negative bacteria are a common endotoxin, and both toxins have effects on human and livestock health. During animal feeding, ZEA as an exotoxin and LPS as an endotoxin have the potential to co-exist in organisms. At present, other studies have only focused on the hazards of single toxins, but there are fewer studies on the coexistence and interaction between ZEA and LPS. Therefore, a further study to investigate the combined toxic effects of different concentrations of ZEA and LPS is warranted. Quercetin (QUE) is a natural flavonoid compound with strong antioxidant and anti-inflammatory properties. It is unclear whether QUE can mitigate the combined effects of ZEA and LPS. IPEC-J2, isolated from the jejunum of non-breastfed neonatal piglets, is an ideal model for the study of epithelial cell transport, intestinal bacterial interactions, and the nutrient modulation of intestinal function. Therefore, the purpose of the present study was to demonstrate the effect of QUE in alleviating the combined toxic effect of ZEA and LPS on IPEC-J2 cell damage. Cell viability was measured after treating IPEC-J2 cells sequentially with 10, 20, 30, 40, 60, 80, and 100 μM ZEA, 1, 10, 50, and 100 μg/mL LPS, and 20, 40, 60, 80, 100, and 200 μM QUE for 24 h. Based on the cell viability results, 20 μM ZEA and 1 μg/mL LPS were selected as the most suitable concentrations for further analysis. For QUE, 20 μM increased the cell viability, while 40-200 μM QUE decreased the cell viability. Therefore, for the subsequent study, 20 μM QUE was selected in combination with 20 μM ZEA and 1 μg/mL LPS. The results showed that QUE increased the cellular viability and decreased the LDH content more compared to the effects of the ZEA+LPS group. At the gene level, QUE addition up-regulated the expression of Nrf2, HO-1, SOD2, and NQO1 at the gene or protein level compared to those of the ZEA+LPS group. The measurement of tight junction-related genes and proteins showed QUE up-regulated the expression of Claudin, ZO-1, and Occludin genes and proteins more than in the ZEA+LPS group. QUE addition reduced the rate of apoptosis more than that in the ZEA+LPS group. The expressions of Bcl-2 and Bax were examined at the gene level, and QUE addition significantly reduced the Bax gene expression level compared to that of the ZEA+LPS group, but there was no apparent variation in the expression level of Bcl-2. In summary, QUE can alleviate the combined toxic effects of ZEA and LPS on IPEC-J2 cells via modulating the Nrf2 signaling pathway, up-regulating the expression of antioxidative genes, and enhancing the intestinal barrier.

Project description:Researches have shown that dietary zearalenone (ZEA) caused oxidative stress in the liver and reproductive organs of postweaning gilts. However, information on the effects of ZEA on oxidative stress of the small intestine in the piglets is limited. The objective of this study was to determine the effects of ZEA exposure on oxidative stress, the Kelch-like erythroid cell-derived protein with CNC homology (ECH)-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and on immunohistochemistry of the jejunum in postweaning gilts. A 35-d feeding experiment using 40 postweaning gilts (Landrace × Yorkshire × Duroc) with an average BW of 14.01 ± 0.86 kg in 4 groups fed corn-soybean meal-based diets containing 0, 0.5, 1.0, and 1.5 mg ZEA/kg was conducted. The jejunum was obtained at the end of the experiment and used for analyses. The results showed that the activities of total superoxide dismutase and glutathione peroxidase and the relative expressions of Keap1 mRNA and protein in the jejunum linearly and quadratically decreased (P < 0.05) with increasing concentrations of ZEA in the diets. The malondialdehyde content, the integrated optical density of Nrf2 and glutathione peroxidase 1 (GPX1), and the relative expressions of Nrf2, GPX1, quinone oxidoreductase 1 (NQO1), and modifier subunit of glutamate-cysteine ligase (GCLM) mRNA and proteins linearly and quadratically increased (P < 0.05) with increasing levels of ZEA. Immunohistochemical analysis showed that Nrf2 and GPX1 immunoreactivity was enhanced by the ZEA treatments, and block localization of yellow and brown immunoreactive substances in the jejunum was observed with increasing levels of ZEA. The results suggest that ingested ZEA induced oxidative stress in the jejunum in postweaning gilts through upregulation of the Keap1-Nrf2 signaling pathway and downstream target genes NQO1, HO1, and GCLM, indicating the important role of the Keap1-Nrf2 signaling pathway in oxidative stress induced by ZEA in the jejunum of the postweaning piglets.

Dataset Information

DL-Selenomethionine Alleviates Oxidative Stress Induced by Zearalenone via Nrf2/Keap1 Signaling Pathway in IPEC-J2 Cells.

Publications

DL-Selenomethionine Alleviates Oxidative Stress Induced by Zearalenone via Nrf2/Keap1 Signaling Pathway in IPEC-J2 Cells.

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