Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
J Agric Food Chem. 2020 Jul 22;68(29):7757-7764. doi: 10.1021/acs.jafc.0c01943. Epub 2020 Jul 9.
Juveniles are considered as one of the most vulnerable population groups concerning mycotoxins and their modified forms. The weaning stage is a particularly vulnerable period in the life of mammals, reflected in intestinal and immune dysfunction. The current study investigated the toxicokinetic (TK) characteristics of zearalenone (ZEN), zearalenone-14-glucoside (ZEN14G), and zearalenone-14-sulfate (ZEN14S) in weaned (4-week-old) piglets, by means of oral and intravenous administration of equimolar doses, i.e., 331, 500, and 415 μg/kg bodyweight, respectively. Plasma and urine were sampled pre- and post-administration and were quantitatively analyzed for ZEN, ZEN14G, ZEN14S, and metabolites by liquid chromatography-high-resolution mass spectrometry. Tailor-made TK models were elaborated to process data. A statistical comparison of the results was performed with TK data obtained in a previously reported study in pigs of 8 weeks of age. Additionally, porcine plasma protein binding was determined to support TK findings. The TK results for ZEN, ZEN14G, and ZEN14S, obtained in 4- and 8-week-old pigs, revealed significant age-related differences, based on differences in intestinal permeability, body fat content, gastrointestinal transit time, and biotransformation, with a special emphasis on an increased absorbed fraction of ZEN14G, i.e., 94 vs 61% in 4- compared to 8-week-old pigs. Since the growing pig has been reported to be a suitable pediatric animal model for humans concerning TK processes, these results may contribute to refine the risk assessment concerning modified ZEN forms in juvenile animals and humans.
幼畜被认为是最易受真菌毒素及其修饰形式影响的人群之一。断奶期是哺乳动物生命中特别脆弱的时期，表现为肠道和免疫功能障碍。本研究通过口服和静脉注射等摩尔剂量（分别为 331、500 和 415μg/kg 体重）的玉米赤霉烯酮（ZEN）、玉米赤霉烯酮-14-葡萄糖苷（ZEN14G）和玉米赤霉烯酮-14-硫酸盐（ZEN14S），研究了断奶（4 周龄）仔猪的毒代动力学（TK）特征。给药前和给药后采集血浆和尿液样本，并通过液相色谱-高分辨质谱定量分析 ZEN、ZEN14G、ZEN14S 和代谢物。详细阐述了定制的 TK 模型来处理数据。通过与之前在 8 周龄猪中进行的研究中获得的 TK 数据进行统计学比较，对结果进行了比较。此外，还测定了猪血浆蛋白结合率以支持 TK 发现。在 4 周龄和 8 周龄猪中获得的 ZEN、ZEN14G 和 ZEN14S 的 TK 结果表明，基于肠道通透性、体脂肪含量、胃肠道转运时间和生物转化的差异，与年龄相关存在显著差异，特别是 ZEN14G 的吸收分数增加，即 4 周龄猪比 8 周龄猪增加 94%比 61%。由于生长猪被报道是研究人类 TK 过程的合适儿科动物模型，因此这些结果可能有助于完善关于幼年动物和人类中修饰的 ZEN 形式的风险评估。
