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低剂量玉米赤霉烯酮及其在未成熟母猪肠道不同节段的转移因子与雌激素受体表达的相关性研究方案。

Correlations between Low Doses of Zearalenone, Its Carryover Factor and Estrogen Receptor Expression in Different Segments of the Intestines in Pre-Pubertal Gilts-A Study Protocol.

机构信息

Department of Veterinary Prevention and Feed Hygiene, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 13, 10-718 Olsztyn, Poland.

Department of Environmental Biotechnology, Faculty of Environmental Sciences and Fisheries, University of Warmia and Mazury in Olsztyn, Słoneczna 45G, 10-719 Olsztyn, Poland.

出版信息

Toxins (Basel). 2021 May 26;13(6):379. doi: 10.3390/toxins13060379.

DOI:10.3390/toxins13060379
PMID:34073248
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8227742/
Abstract

Plant materials can be contaminated with 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 RNA expression of estrogen receptor alfa (ER) and estrogen receptor beta (ER) genes, and the RNA 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, = 15) and three experimental groups (group ZEN5, group ZEN10, and group ZEN15; = 15). Group ZEN5 will be administered 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.

摘要

植物材料可能会受到真菌毒素及其衍生物的污染,这些毒素对人类和动物的毒性可能处于亚临床状态。玉米赤霉烯酮(ZEN)是一种低分子量化合物,是农作物中霉菌作为次生代谢物产生的。本研究的目的将是分析极低单调剂量 ZEN(5、10 和 15μg ZEN/kg 体重-BW,42 天)与这种真菌毒素及其从肠内容物到肠壁的选择性代谢物的转移、雌激素受体 alfa(ER)和雌激素受体 beta(ER)基因的 RNA 表达以及肠道黏膜中选定结肠酶(CYP1A1 和 GSTP1)的基因调节 RNA 表达之间的体内相关性。在 60 头初始体重为 14.5±2kg 的临床健康仔猪上进行体内实验。将仔猪随机分为对照组(C 组,n=15)和三个实验组(ZEN5 组、ZEN10 组和 ZEN15 组;n=15)。ZEN5 组给予 5μg ZEN/kg BW(MABEL),ZEN10 组给予 10μg ZEN/kg BW(NOAEL),ZEN15 组给予 15μg ZEN/kg BW(低 LOAEL)。在每组中,将有 5 头动物在分析日期 1(暴露第 7 天)、2(暴露第 21 天)和 3(暴露第 42 天)被安乐死。用于体外分析的样本将从以下区域切除的肠段中采集:十二指肠的第三(水平)部分、空肠、回肠、盲肠、升结肠、横结肠和降结肠。实验材料将在特殊条件下收集,并将其运送到专门的实验室,在那里获得样本进行进一步分析。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ad9/8227742/6b69bdbc16e5/toxins-13-00379-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ad9/8227742/6b69bdbc16e5/toxins-13-00379-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ad9/8227742/6b69bdbc16e5/toxins-13-00379-g001.jpg

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本文引用的文献

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Occurrence, Impact on Agriculture, Human Health, and Management Strategies of Zearalenone in Food and Feed: A Review.食品和饲料中玉米赤霉烯酮的发生、对农业、人类健康的影响及管理策略:综述
Toxins (Basel). 2021 Jan 26;13(2):92. doi: 10.3390/toxins13020092.
2
In silico methods for metabolomic and toxicity prediction of zearalenone, α-zearalenone and β-zearalenone.计算机方法在玉米赤霉烯酮、α-玉米赤霉烯酮和β-玉米赤霉烯酮的代谢组学和毒性预测中的应用。
Food Chem Toxicol. 2020 Dec;146:111818. doi: 10.1016/j.fct.2020.111818. Epub 2020 Oct 21.
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Risks for animal health related to the presence of zearalenone and its modified forms in feed.
暴露于低浓度玉米赤霉烯酮和未成年母猪特定甾体敏感组织中内源性激素的动态平衡和浓度变化。
Toxins (Basel). 2022 Nov 11;14(11):790. doi: 10.3390/toxins14110790.
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Carry-Over of Zearalenone and Its Metabolites to Intestinal Tissues and the Expression of CYP1A1 and GSTπ1 in the Colon of Gilts before Puberty.青春期前母猪肠道组织中玉米赤霉烯酮及其代谢物的残留及其对 CYP1A1 和 GSTπ1 的表达。
Toxins (Basel). 2022 May 18;14(5):354. doi: 10.3390/toxins14050354.
饲料中玉米赤霉烯酮及其变体对动物健康的风险。
EFSA J. 2017 Jul 31;15(7):e04851. doi: 10.2903/j.efsa.2017.4851. eCollection 2017 Jul.
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C/EBPβ mediates NQO1 and GSTP1 anti-oxidative reductases expression in glioblastoma, promoting brain tumor proliferation.C/EBPβ 介导 NQO1 和 GSTP1 抗氧化还原酶在神经胶质瘤中的表达,促进脑肿瘤增殖。
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First in human dose calculation of a single-chain bispecific antibody targeting glioma using the MABEL approach.应用 MABEL 方法计算针对神经胶质瘤的单链双特异性抗体的人体首剂量。
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Curr Opin Toxicol. 2019 Aug;16:49-57. doi: 10.1016/j.cotox.2019.04.003. Epub 2019 Apr 19.
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Toxicon. 2020 Jan 15;173:75-93. doi: 10.1016/j.toxicon.2019.11.006. Epub 2019 Nov 14.
8
Imbalance in the Blood Concentrations of Selected Steroids in Pre-pubertal Gilts Depending on the Time of Exposure to Low Doses of Zearalenone.根据暴露于低剂量玉米赤霉烯酮时间的不同,青春期前母猪血液中选定类固醇浓度失衡。
Toxins (Basel). 2019 Sep 25;11(10):561. doi: 10.3390/toxins11100561.
9
Time-Dependent Changes in the Intestinal Microbiome of Gilts Exposed to Low Zearalenone Doses.暴露于低浓度玉米赤霉烯酮的母猪肠道微生物组的时间依赖性变化。
Toxins (Basel). 2019 May 24;11(5):296. doi: 10.3390/toxins11050296.
10
Autoimmune diseases: Role of steroid hormones.自身免疫性疾病:类固醇激素的作用。
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