Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, 180 chemin de Tournefeuille, 31027, Toulouse Cedex 3, France.
BIOMIN Research Center, Technopark 1, 3430, Tulln, Austria.
Arch Toxicol. 2018 Nov;92(11):3381-3389. doi: 10.1007/s00204-018-2293-x. Epub 2018 Aug 31.
Deoxynivalenol (DON) is the most abundant trichothecene in food and feed. It causes both acute and chronic disorders of the human and animal intestine, liver and the immune system. The structural basis for the toxicity of DON has not been fully elucidated. Using the pig as a target and a model species for human, the toxicity of DON and its deepoxy-metabolite (DOM-1) was compared. Animals were exposed by gavage to 1 and 0.5 nmol toxin/kg b.w./day for 2 and 3 weeks respectively. Whatever the dose/duration, DOM-1 was less toxic than DON in terms of weight gain and emesis. In the 3-week experiment, animals were vaccinated with ovalbumin, and their immune response was analyzed in addition to tissue morphology, biochemistry and hematology. DON impaired the morphology of the jejunum and the ileum, reduced villi height, decreased E-cadherin expression and modified the intestinal expression of cytokines. Similarly, DON induced hepatotoxicity as indicated by the lesion score and the blood biochemistry. By contrast, DOM-1 only induced minimal intestinal toxicity and did not trigger hepatotoxicity. As far as the immune response was concerned, the effects of ingesting DOM-1 were similar to those caused by DON, as measured by histopathology of lymphoid organs, PCNA expression and the specific antibody response. Taken together, these data demonstrated that DOM-1, a microbial detoxification product of DON, was not toxic in the sensitive pig model but retained some immune-modulatory properties of DON, especially its ability to stimulate a specific antibody response during a vaccination protocol.
脱氧雪腐镰刀菌烯醇（DON）是食品和饲料中含量最丰富的一种单端孢霉烯族毒素。它会引起人和动物的肠道、肝脏和免疫系统的急性和慢性紊乱。DON 的毒性的结构基础尚未完全阐明。本研究以猪为研究对象，利用其作为人类的模型物种，比较 DON 及其去氧代谢物（DOM-1）的毒性。动物通过灌胃暴露于 1 和 0.5 nmol 毒素/kg.b.w./天，分别持续 2 和 3 周。无论剂量/时间如何，DOM-1 的毒性均低于 DON，表现在体重增加和呕吐方面。在 3 周的实验中，动物用卵清蛋白进行了疫苗接种，除了组织形态、生物化学和血液学分析外，还分析了它们的免疫反应。DON 损害了空肠和回肠的形态，降低了绒毛高度，减少了 E-钙粘蛋白的表达，并改变了肠道细胞因子的表达。同样，DON 诱导了肝毒性，表现为病变评分和血液生物化学的变化。相比之下，DOM-1 仅引起轻微的肠道毒性，不会引发肝毒性。就免疫反应而言，摄入 DOM-1 的影响与 DON 引起的影响相似，这可以通过淋巴器官的组织病理学、PCNA 表达和特异性抗体反应来衡量。总之，这些数据表明，DON 的微生物解毒产物 DOM-1 在敏感的猪模型中没有毒性，但保留了 DON 的一些免疫调节特性，特别是在疫苗接种方案中刺激特异性抗体反应的能力。
