Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, Calea Bucuresti No. 1, Balotesti, Ilfov 077015, Romania.
Toxicol In Vitro. 2011 Dec;25(8):1981-8. doi: 10.1016/j.tiv.2011.06.022. Epub 2011 Jul 8.
Zearalenone (ZEN), a mycotoxin produced by several Fusarium spp., is most commonly found as a contaminant in stored grain and has chronic estrogenic effects on mammals. In this in vitro study, we compared the effects of zearalenone (ZEN) and some of its derivatives: α-zearalenol (α-ZOL), β-zearalenol (β-ZOL), and zearalanone (ZAN) on several peripheral blood mononuclear cell (PBMC) parameters: cytotoxicity, proliferation, as well as antibody and cytokine synthesis. The amounts of toxins necessary to inhibit viability, in a dehydrogenase enzyme activity assay (MTT test), by 50% were: 22.7 μM for ZEN, 29.1 μM for α-ZOL, 17.3 μM for β-ZOL and 26.3 μM for ZAN. The administration of 10 μM toxin induced a decrease in the ConA stimulated proliferation of PBMC by 19.6% for ZAN, 45.4% for ZEN, 43.6% for α-ZOL and 85.2% for β-ZOL, when compared to the control stimulated cells. Also, ZEN and its metabolites at concentrations higher than 5 μM induced a significant decrease of the IgG, IgA or IgM levels. Concentrations of 5 and 10 μM of ZEN and ZAN significantly decreased the TNF-α synthesis in the supernatant of the stimulated cells; 10 μM of ZAN also decreased IL-8 synthesis. In conclusion, our results show that ZEN and ZEN derivatives altered several parameters of the humoral and cellular immune response. Therefore, our results are clinically relevant as ZEN and its metabolites are frequent contaminants of animal feed and we have shown that intoxicated animals are incapable of inducing an adequate immune response.
玉米赤霉烯酮（ZEN）是由几种镰刀菌属产生的真菌毒素，通常作为储存谷物的污染物存在，对哺乳动物具有慢性雌激素作用。在这项体外研究中，我们比较了玉米赤霉烯酮（ZEN）及其一些衍生物：α-玉米赤霉醇（α-ZOL）、β-玉米赤霉醇（β-ZOL）和玉米赤霉酮（ZAN）对几种外周血单个核细胞（PBMC）参数的影响：细胞毒性、增殖以及抗体和细胞因子合成。在脱氢酶活性测定（MTT 试验）中，抑制活力 50%所需的毒素量分别为：ZEN 为 22.7 μM，α-ZOL 为 29.1 μM，β-ZOL 为 17.3 μM，ZAN 为 26.3 μM。10 μM 毒素处理导致 ZAN 刺激的 PBMC 增殖减少 19.6%，ZEN 减少 45.4%，α-ZOL 减少 43.6%，β-ZOL 减少 85.2%，与对照刺激细胞相比。此外，ZEN 及其代谢物在浓度高于 5 μM 时会显著降低 IgG、IgA 或 IgM 水平。5 和 10 μM 的 ZEN 和 ZAN 浓度显著降低了刺激细胞上清液中 TNF-α的合成；10 μM 的 ZAN 还降低了 IL-8 的合成。总之，我们的结果表明 ZEN 和 ZEN 衍生物改变了体液和细胞免疫反应的几个参数。因此，我们的结果具有临床相关性，因为 ZEN 和其代谢物是动物饲料的常见污染物，我们已经表明，中毒动物不能诱导适当的免疫反应。
