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Murine immunomodulation by low-dose dietary deoxynivalenol and improved detection methods for deoxynivalenol.

机译：低剂量饮食中脱氧雪茄烯醇对小鼠的免疫调节及改良的脱氧雪茄烯醇检测方法。

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摘要

Deoxynivalenol (DON) is a mycotoxin naturally occurring in worldwide grain supplies and has caused gastrointestinal disease, in humans and animals, and immunotoxicity in animals. Methods were optimized for analysis and screening of food samples for DON. Caffeine was a suitable internal standard for analytical detection of DON in wheat samples using high performance liquid chromatography (HPLC). This method will allow analysis of samples using a stable and inexpensive compound not likely to be found in most samples of interest. A bioassay was used to screen for DON in a variety of food samples. Human K-562 erythroleukemia cells, modeling immune stem cells, were incubated with wheat and corn extracts in media, cell proliferation assessed by the MTS dye reduction assay. Samples containing DON ranged in concentrations from 204 to 3792 ng DON/g food strongly correlating with HPLC analysis. This sensitive bioassay may serve as an inexpensive low-tech alternative for screening food samples or products of DON detoxification studies. We hypothesized that acute exercise stress would exacerbate immunosuppressive effects of dietary DON. Male BALB/c mice were fed 0 or 2 mg DON/kg diet for 14 days (n = 12 per dose), then half of each dose were exercised to fatigue. Non-exercised DON-fed mice showed significant splenocyte proliferation suppression and increased IL-4 expression. Antibody response to sheep red blood cells was significantly less for exercised DON-fed mice with increased IL-2 expression. Exercise caused elevated serum corticosterone levels. Exercise stress protected against DON-mediated suppression of splenocyte proliferation, perhaps mediated by stress hormone effects on differential cytokine expression. This interaction was investigated further with BALB/c male mice fed 0, 1 or 2 ppm DON for 28 days then half of each dose was exercised to fatigue. Exercise was inhibitory for IL-4, NK cytotoxicity, spleen: body weight ratio, blood lymphocytes, hemoglobin, hematocrit but caused elevated blood neutrophils. Dietary DON at 2 ppm inhibited weight gain, red blood cell numbers and hematocrit but increased feed intake. DON fed at 1 ppm stimulated NK cytotoxicity, PFCs, and spontaneous IFN-gamma secretion. This is the first report of in vivo immunostimulatory effects of sub-chronic low dose DON feeding.
机译：脱氧雪腐烯醇（DON）是一种真菌毒素，天然存在于世界各地的谷物供应中，已引起人类和动物的胃肠道疾病以及动物的免疫毒性。方法进行了优化，以分析和筛选食物样品中的呕吐毒素。咖啡因是使用高效液相色谱（HPLC）分析检测小麦样品中DON的合适内标。这种方法将允许使用稳定和廉价的化合物分析样品，而这些化合物在大多数目标样品中都不太可能找到。生物测定法用于筛查各种食品样品中的DON。将模拟免疫干细胞的人K-562红白血病细胞与小麦和玉米提取物在培养基中孵育，并通过MTS染料还原测定法评估细胞增殖。含DON的样品浓度范围为204至3792 ng DON / g食品，与HPLC分析密切相关。这种灵敏的生物测定法可以作为一种廉价的低技术替代品，用于筛查DON解毒研究的食物样品或产品。我们假设急性运动压力会加剧饮食中呕吐毒素的免疫抑制作用。给雄性BALB / c小鼠饲喂0或2 mg DON / kg饮食，持续14天（每剂量n = 12），然后将每个剂量的一半运动至疲劳。非运动的DON喂养的小鼠表现出明显的脾细胞增殖抑制和增加的IL-4表达。对于具有增加的IL-2表达的运动的DON喂养的小鼠，对绵羊红细胞的抗体应答显着降低。运动导致血清皮质酮水平升高。运动应激可抵抗DON介导的脾细胞增殖抑制，也许是由应激激素对差异化细胞因子表达的介导的。用饲喂0、1或2 ppm DON的BALB / c雄性小鼠28天进一步研究了这种相互作用，然后将每种剂量的一半进行疲劳训练。运动对IL-4，NK细胞毒性，脾脏：体重比，血液淋巴细胞，血红蛋白，血细胞比容有抑制作用，但会引起血液中性粒细胞升高。日粮中DON的含量为2 ppm可抑制体重增加，红细胞数量和血细胞比容，但可增加采食量。以1 ppm喂食的DON刺激了NK细胞毒性，PFC和自发的IFN-γ分泌。这是亚慢性低剂量DON喂养的体内免疫刺激作用的首次报道。

著录项

  • 作者

    Landgren, Cindy A.;

  • 作者单位

    Iowa State University.;

  • 授予单位 Iowa State University.;
  • 学科 Health Sciences Toxicology.
  • 学位 Ph.D.
  • 年度 2005
  • 页码 174 p.
  • 总页数 174
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 毒物学（毒理学）;
  • 关键词

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