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.
Arch Toxicol. 2020 Feb;94(2):417-425. doi: 10.1007/s00204-019-02644-x. Epub 2019 Dec 13.
Age-related differences in toxicokinetic processes of deoxynivalenol (DON) and deoxynivalenol-3-glucoside (DON3G) were studied. DON3G [55.7 µg/kg bodyweight (BW)] and an equimolar dose of DON (36 µg/kg BW) were administered to weaned piglets (4 weeks old) by single intravenous and oral administration in a double two-way cross-over design. Systemic and portal blood was sampled at different time points pre- and post-administration and plasma concentrations of DON, DON3G and their metabolites were quantified using validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography-high-resolution mass spectrometry (LC-HRMS) methods. Data were processed using tailor-made compartmental toxicokinetic (TK) models to accurately estimate TK parameters. Results were statistically compared to data obtained in a previous study on 11-week-old pigs using identical experimental conditions. Significant age-related differences in intestinal and systemic exposure to both DON and DON3G were noted. Most remarkably, a significant difference was found for the absorbed fraction of DON3G, after presystemic hydrolysis to DON, in weaned piglets compared to 11-week-old piglets (83% vs 16%, respectively), assumed to be mainly attributed to the higher intestinal permeability of weaned piglets. Other differences in TK parameters could be assigned to a higher water/fat body ratio and longer gastrointestinal transit time of weaned piglets. Results may further refine current risk assessment concerning DON and DON3G in animals. Additionally, since piglets possibly serve as a human paediatric surrogate model, results may be extrapolated to human infants.
研究了脱氧雪腐镰刀菌烯醇（DON）和脱氧雪腐镰刀菌烯醇-3-葡萄糖苷（DON3G）在毒代动力学过程中的年龄相关差异。采用双二向交叉设计，通过单次静脉内和口服给予断奶仔猪（4 周龄）DON3G[55.7µg/kg 体重（BW）]和等摩尔剂量的 DON（36µg/kg BW）。在给药前和给药后不同时间点采集系统和门脉血液，并使用经过验证的液相色谱-串联质谱（LC-MS/MS）和液相色谱-高分辨率质谱（LC-HRMS）方法定量测定 DON、DON3G 及其代谢物的血浆浓度。使用定制的房室毒代动力学（TK）模型处理数据，以准确估计 TK 参数。使用相同的实验条件，将结果与之前在 11 周龄猪上进行的研究中获得的数据进行统计学比较。结果表明，断奶仔猪和 11 周龄仔猪在肠道和全身暴露于 DON 和 DON3G 方面存在显著的年龄相关差异。最显著的是，与 11 周龄仔猪相比，断奶仔猪体内 DON3G 的吸收分数（经前体水解为 DON 后）存在显著差异（分别为 83%和 16%），这主要归因于断奶仔猪较高的肠道通透性。其他 TK 参数的差异可归因于断奶仔猪较高的水/脂肪体比和较长的胃肠道转运时间。结果可能会进一步完善目前对动物中 DON 和 DON3G 的风险评估。此外，由于仔猪可能作为人类儿科替代模型，因此结果可能会外推至人类婴儿。
