Universidade Federal do Tocantins, Araguaína 77824-838, Brazil.
Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, 31027 Toulouse, France.
Toxins (Basel). 2018 May 1;10(5):183. doi: 10.3390/toxins10050183.
An increase in the occurrence of ergot alkaloids (EAs) contamination has been observed in North America and Europe in recent years. These toxins are well known for their effects on the circulatory and nervous systems. The aim of this study was to investigate the effect of EAs on the liver and on the intestine using the pig both as a target species and as a non-rodent model for human. Three groups of 24 weaned piglets were exposed for 28 days to control feed or feed contaminated with 1.2 or 2.5 g of sclerotia/kg, i.e., at doses close to EU regulatory limits. Contaminated diets significantly reduced feed intake and consequently growth performance. In the liver, alteration of the tissue, including development of inflammatory infiltrates, vacuolization, apoptosis and necrosis of hepatocytes as well as presence of enlarged hepatocytes (megalocytes) were observed. In the jejunum, EAs reduced villi height and increased damage to the epithelium, reduced the number of mucus-producing cells and upregulated mRNA coding for different tight junction proteins such as claudins 3 and 4. In conclusion, in term of animal health, our data indicate that feed contaminated at the regulatory limits induces lesions in liver and intestine suggesting that this limit should be lowered for pigs. In term of human health, we establish a lowest observed adverse effect level (LOAEL) of 100 μg/kg body weight (bw) per day, lower than the benchmark dose limit (BMDL) retained by European Food Safety Authority (EFSA) to set the tolerable daily intake, suggesting also that regulatory limit should be revised.
近年来，在北美和欧洲观察到麦角生物碱（EAs）污染的发生率增加。这些毒素以其对循环和神经系统的影响而闻名。本研究的目的是使用猪作为靶物种和人类的非啮齿动物模型，研究 EAs 对肝脏和肠道的影响。三组 24 日龄断奶仔猪在 28 天内暴露于对照饲料或污染饲料中，污染饲料中的麦角生物碱含量分别为 1.2 或 2.5 g/kg 麦角生物碱，接近欧盟监管限量。污染饲料显著降低了采食量，进而降低了生长性能。在肝脏中，观察到组织改变，包括炎症浸润、空泡形成、肝细胞凋亡和坏死，以及大肝细胞（巨肝细胞）的存在。在空肠中，EAs 降低了绒毛高度，增加了对上皮的损伤，减少了产生粘液的细胞数量，并上调了编码不同紧密连接蛋白（如 Claudin 3 和 4）的 mRNA。总之，就动物健康而言，我们的数据表明，在监管限量下污染的饲料会引起肝脏和肠道的损伤，这表明该限量应该降低。就人类健康而言，我们确定了 100 μg/kg 体重/天的最低观察到的不良效应水平（LOAEL），低于欧洲食品安全局（EFSA）为确定可耐受每日摄入量而保留的基准剂量限值（BMDL），这也表明监管限量应进行修订。
