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Deoxynivalenol: mechanisms of action, human exposure, and toxicological relevance

机译：脱氧雪腐烯醇：作用机理，人体暴露和毒理学意义

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摘要

The trichothecene mycotoxin deoxynivalenol (DON) is produced in wheat, barley and corn following infestation by the fungus Fusarium in the field and during storage. Colloquially known as “vomitoxin” because of its emetic effects in pigs, DON has been associated with human gastroenteritis. Since DON is commonly detected in cereal foods, there are significant questions regarding the risks of acute poisoning and chronic effects posed to persons ingesting this trichothecene. A further challenge is how to best manage perceived risks without rendering critical food staples unavailable to an ever-expanding world population. In experimental animal models, acute DON poisoning causes emesis, whereas chronic low-dose exposure elicits anorexia, growth retardation, immunotoxicity as well as impaired reproduction and development resulting from maternal toxicity. Pathophysiologic effects associated with DON include altered neuroendocrine signaling, proinflammatory gene induction, disruption of the growth hormone axis, and altered gut integrity. At the cellular level, DON induces ribotoxic stress thereby disrupting macromolecule synthesis, cell signaling, differentiation, proliferation, and death. There is a need to better understand the mechanistic linkages between these early dose-dependent molecular effects and relevant pathological sequelae. Epidemiological studies are needed to determine if relationships exist between consumption of high DON levels and incidence of both gastroenteritis and potential chronic diseases. From the perspective of human health translation, a particularly exciting development is the availability of biomarkers of exposure (e.g. DON glucuronide) and effect (e.g. IGF1) now make it possible to study the relationship between DON consumption and growth retardation in susceptible human populations such as children and vegetarians. Ultimately, a fusion of basic and translational research is needed to validate or refine existing risk assessments and regulatory standards for this common mycotoxin.
机译：在田间和贮藏期间，真菌镰刀菌侵染后，小麦，大麦和玉米中产生了天花粉真菌毒素脱氧雪腐烯酚（DON）。由于在猪中具有催吐作用，俗称“呕吐毒素”，呕吐毒素与人类胃肠炎有关。由于谷物食品中通常检测到呕吐毒素，因此对于摄入这种天花粉剂的人造成急性中毒的风险和慢性影响存在重大问题。另一个挑战是如何最好地管理感知到的风险，而又不会使不断增长的世界人口无法获得重要的粮食主粮。在实验动物模型中，急性DON中毒会引起呕吐，而长期低剂量暴露会引起厌食，生长迟缓，免疫毒性以及由母体毒性导致的生殖和发育受损。与DON相关的病理生理影响包括神经内分泌信号的改变，促炎基因的诱导，生长激素轴的破坏和肠道完整性的改变。在细胞水平上，DON诱导核糖毒性应激，从而破坏大分子合成，细胞信号传导，分化，增殖和死亡。有必要更好地了解这些早期剂量依赖性分子效应与相关病理后遗症之间的机制联系。需要进行流行病学研究，以确定高DON摄入量与胃肠炎和潜在慢性疾病的发病率之间是否存在关系。从人类健康翻译的角度来看，一个特别令人振奋的发展是暴露的生物标志物（例如DON葡萄糖苷酸）和效果（例如IGF1）的可用性现在使得研究易感人群中DON消费与生长迟缓之间的关系成为可能，例如儿童和素食主义者。最终，需要对基础研究和转化研究进行融合，以验证或完善这种常见真菌毒素的现有风险评估和监管标准。

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