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Investigation of age-related differences in toxicokinetic processes of deoxynivalenol and deoxynivalenol-3-glucoside in weaned piglets.
Archives of Toxicology ( IF 4.8 ) Pub Date : 2019-12-13 , DOI: 10.1007/s00204-019-02644-x
Amelie Catteuw 1 , Mathias Devreese 1 , Siegrid De Baere 1 , Gunther Antonissen 1, 2 , Lada Ivanova 3 , Silvio Uhlig 3 , Ann Martens 4 , Sarah De Saeger 5 , Marthe De Boevre 5 , Siska Croubels 1
Affiliation  

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.

中文翻译:

断奶仔猪中脱氧雪茄烯醇和脱氧雪茄烯醇-3-葡萄糖苷毒代动力学过程中年龄相关差异的研究。

研究了脱氧雪茄烯醇(DON)和脱氧雪茄烯醇-3-葡萄糖苷(DON3G)的毒代动力学过程中与年龄有关的差异。断奶仔猪(4周龄)通过双双向双向设计,分别向断奶仔猪(4周龄)施用DON3G [55.7 µg / kg体重(BW)]和等摩尔剂量的DON(36 µg / kg BW)。 。在给药前和给药后的不同时间点对全身和门静脉血进行采样,并使用经验证的液相色谱-串联质谱(LC-MS / MS)和液相色谱-高分辨率对DON,DON3G及其代谢产物的血浆浓度进行定量质谱(LC-HRMS)方法。使用量身定制的区室代谢动力学(TK)模型处理数据,以准确估算TK参数。将结果与先前研究中使用相同实验条件对11周龄的猪获得的数据进行统计比较。肠道和全身暴露于DON和DON3G的年龄相关显着差异。最显着的是,断奶仔猪与11周龄仔猪相比,在被系统分解为DON后,DON3G的吸收分数有显着差异(分别为83%和16%),这主要归因于较高的断奶仔猪的肠道通透性。TK参数的其他差异可归因于断奶仔猪更高的水/脂肪比和更长的胃肠道通过时间。结果可能会进一步完善当前有关动物中DON和DON3G的风险评估。此外,由于仔猪可能会成为人类的儿科替代模型,
更新日期:2019-12-17
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