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猪的口服和静脉内伏马菌素暴露-评价毒代动力学和解毒的单次剂量处理实验。

Oral and Intravenous Fumonisin Exposure in Pigs-A Single-Dose Treatment Experiment Evaluating Toxicokinetics and Detoxification.

机构信息

Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, 38116 Braunschweig, Germany.

BIOMIN Holding GmbH, BIOMIN Research Center, 3430 Tulln, Austria.

出版信息

Toxins (Basel). 2018 Apr 5;10(4):150. doi: 10.3390/toxins10040150.

Abstract

We examined the toxicokinetics of fumonisin B₁ (FB1) and its main metabolites after single dose application () of 139 nmol FB1 or hydrolyzed FB1 (HFB1)/kg bodyweight (BW) in barrows (BW: 34.4 kg ± 2.7 kg), as well as the toxicokinetics of FB1, FB2, FB3 and FB1 bioavailability from oral exposure (3425 nmol FB1/kg BW, on top of ration). Additionally, detoxification efficacy of FumD (240 U/kg feed; 3321 nmol FB1/kg BW), a fumonisin esterase, was examined for oral fumonisin application. Urine and feces were collected quantitatively and serum samples were taken over a period of 120 h. Serum toxicokinetics of FB1 showed a short distribution half-life of 6 min followed by a longer elimination half-life of 36 min. After HFB1 administration, serum clearance was three times higher compared to FB1 group (5.6 and 1.8 L/kg/h respectively) which together with a 5-times higher volume of distribution indicates that HFB1 is more rapidly cleared from systemic circulation but distributed more extensively into the extravasal space than FB1. The bioavailability of FB1 in orally exposed pigs was 5.2% (incl. metabolites). Moreover, we found a significant reduction of FB1 bioavailability by 90% caused by the action of fumonisin esterase in the gastrointestinal tract, clearly demonstrating the efficacy of FumD.

摘要

我们研究了单剂量应用 139 nmol FB1 或水解 FB1(HFB1)/kg 体重(BW)(BW:34.4 kg ± 2.7 kg)后,福莫丁 B₁(FB1)及其主要代谢物的毒代动力学,以及口服暴露(在日粮之上 3425 nmol FB1/kg BW)后 FB1、FB2、FB3 和 FB1 生物利用度的毒代动力学。此外,还研究了福莫丁酯酶(FumD)(240 U/kg 饲料;3321 nmol FB1/kg BW)对口服福莫丁应用的解毒功效。定量收集尿液和粪便,并在 120 h 内采集血清样本。血清中 FB1 的毒代动力学显示,其分布半衰期较短,为 6 min,随后消除半衰期较长,为 36 min。与 FB1 组相比,HFB1 给药后血清清除率高 3 倍(分别为 5.6 和 1.8 L/kg/h),而分布容积高 5 倍表明 HFB1 从全身循环中更快清除,但比 FB1 更广泛地分布到血管外空间。口服暴露的猪 FB1 的生物利用度为 5.2%(包括代谢物)。此外,我们发现福莫丁酯酶在胃肠道中的作用使 FB1 的生物利用度显著降低了 90%,这清楚地表明了 FumD 的功效。

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