Emetic responses to T-2 toxin, HT-2 toxin and emetine correspond to plasma elevations of peptide YY3-36 and 5-hydroxytryptamine
Emetic responses to T-2 toxin, HT-2 toxin and emetine correspond to plasma elevations of peptide YY3-36 and 5-hydroxytryptamine
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对 T-2 毒素、HT-2 毒素和依米丁的催吐反应与肽 YY 和 5-羟色胺的血浆升高相对应。
DOI：
10.1007/s00204-015-1508-7
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发表时间：
2016-04-01
影响因子：
6.1
通讯作者：
Pestka, James J.
中科院分区：
文献类型：
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作者：
Wu, Wenda;Zhou, Hui-Ren;Pestka, James J.
单端孢菌素霉菌毒素是一类强效翻译抑制剂，与人类和动物胃肠炎的食源性爆发有关，其中呕吐是临床标志。脱氧雪腐镰刀菌烯醇（DON，呕吐毒素）和其他 B 型单端孢霉烯族化合物先前已被证明会引起水貂呕吐（Neovison vison），并且这种反应与饱腹感激素肽 YY3-36 (PYY3-36) 和神经递质 5-羟色胺 (5-HT) 的分泌直接相关。在这里，我们表征了水貂对 T-2 毒素 (T-2) 和 HT-2 毒素 (HT-2)（两种污染谷物的剧毒 A 型单端孢霉烯族化合物）的催吐反应，并进一步将这些效应与吐根碱（一种天然生物碱，用于药用，众所周知会阻碍翻译并引起呕吐）进行比较。腹膜内（IP）和口服暴露后，所有三种药物均引起呕吐，呕吐事件的持续时间和数量均呈剂量依赖性增加，并且呕吐潜伏期缩短。腹膜内和口服给药后，引起 50% 治疗动物呕吐的 T-2 和 HT-2 剂量 (ED(50)s) 分别为 0.05 和 0.02 mg/kg BW，而腹膜内和口服给药时吐米丁的 ED(50) 分别为 2.0 和 1.0 mg/kg BW。重要的是，口服所有三种毒素都会引起 PYY3-36 和 5-HT 血浆浓度显着升高，这与呕吐相对应。总而言之，结果表明 T-2 和 HT-2 比依米丁更有效，并且所有三种翻译抑制剂引起的呕吐与 PYY3-36 和 5-HT 循环水平的增加同时发生。
Trichothecene mycotoxins are a family of potent translational inhibitors that are associated with foodborne outbreaks of human and animal gastroenteritis in which vomiting is a clinical hallmark. Deoxynivalenol (DON, vomitoxin) and other Type B trichothecenes have been previously demonstrated to cause emesis in the mink (Neovison vison), and this response has been directly linked to secretion of both the satiety hormone peptide YY3-36 (PYY3-36) and neurotransmitter 5-hydroxytryptamine (5-HT). Here, we characterized the emetic responses in the mink to T-2 toxin (T-2) and HT-2 toxin (HT-2), two highly toxic Type A trichothecenes that contaminate cereals, and further compared these effects to those of emetine, a natural alkaloid that is used medicinally and also well known to block translation and cause vomiting. Following intraperitoneal (IP) and oral exposure, all three agents caused vomiting with evident dose-dependent increases in both duration and number of emetic events as well as decreases in latency to emesis. T-2 and HT-2 doses causing emesis in 50 % of treated animals (ED(50)s) were 0.05 and 0.02 mg/kg BW following IP and oral administration, respectively, whereas the ED(50)s for emetine were 2.0 and 1.0 mg/kg BW for IP and oral exposure, respectively. Importantly, oral administration of all three toxins elicited marked elevations in plasma concentrations of PYY3-36 and 5-HT that corresponded to emesis. Taken together, the results suggest that T-2 and HT-2 were much more potent than emetine and that emesis induction by all three translational inhibitors co-occurred with increases in circulating levels of PYY3-36 and 5-HT.