Physiologically based toxicokinetics of serum aflatoxin B1-lysine adduct in F344 rats.
Physiologically based toxicokinetics of serum aflatoxin B1-lysine adduct in F344 rats.
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DOI：
10.1016/j.tox.2012.10.020
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发表时间：
2013-01-07
期刊：
影响因子：
4.5
通讯作者：
Wang, Jia-Sheng
中科院分区：
文献类型：
--
作者：
Qian, Guoqing;Tang, Lili;Wang, Franklin;Guo, Xia;Massey, Michael E.;Williams, Jonathan H.;Phillips, Timothy D.;Wang, Jia-Sheng
黄曲霉毒素B1-赖氨酸加合物（AFB-Lys）是黄曲霉毒素暴露的可靠生物标志物，然而，尚未报道系统的毒代动力学评价。在这项研究中，雄性F344大鼠口服暴露于单次或重复剂量的黄曲霉毒素B1和血清黄曲霉毒素B-Lys的毒代动力学进行了研究。单剂量AFB 1可使血清AFB-Lys水平迅速升高，在4 h达到峰值，随后发生一级消除，半衰期估计为2.31天。基于生理学的药代动力学模型显示，在治疗后2 h和24 h，分别约有3.00-3.90%和1.12-1.98%的AFB 1剂量转化为血清AFB-Lys加合物。在5-25 μg/kg体重的重复AFB 1暴露下，动物血清AFB-Lys水平线性增加5周，导致总体AFB-Lys水平升高1-1.5倍。这表明这种加合物作为重复低剂量暴露的可靠生物标志物的潜力。在75 μg/kg的高剂量暴露下，AFB-Lys水平在2周时达到最大值，随后逐渐下降至接近平台水平，直至5周。总之，本研究使用基于生理学的药代动力学模型和稳健的统计建模分析系统评价了F344大鼠血清AFB-Lys加合物的毒代动力学，并对该生物标志物的毒代动力学提供了明确而清晰的理解。
Aflatoxin B1-lysine adduct (AFB-Lys) is a reliable biomarker for aflatoxin exposure; however, a systematic toxicokinetic evaluation has not been reported. In this study, male F344 rats were orally exposed to single, or repeated, doses of AFB1 and the toxicokinetics of serum AFB-Lys that followed treatments were investigated. A single-dose of AFB1 increased serum AFB-Lys levels rapidly peaking at 4 h, followed by first-order elimination, through which the half-life was estimated to be 2.31 days. A physiologically based pharmacokinetic model showed that approximately 3.00-3.90% and 1.12-1.98% of the administered AFB1 doses were converted to serum AFB-Lys adducts at 2 h and 24 h post treatment, respectively. Repeated AFB1 exposure at 5-25 μg/kg body weight linearly increased serum AFB-Lys levels for 5 weeks in animals, resulting in a 1-1.5 times higher AFB-Lys level overall. This indicates the potential of this adduct as a reliable biomarker for repeated low dose exposure. Higher dose exposure at 75 μg/kg increased the level of AFB-Lys to a maximum at 2 weeks, followed by a gradual decrease to near plateau level up to 5 weeks. In conclusion, this study systematically evaluated the toxicokinetics of serum AFB-Lys adduct in F344 rats using a physiologically based pharmacokinetic model and robust statistical modeling analysis and provided a firm and clear understanding of the toxicokinetics of this biomarker.
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影响因子：
3.8
作者：
Kensler, Thomas W.;Roebuck, Bill D.;Groopman, John D.
通讯作者：
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影响因子：
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作者：
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作者：
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TURSI, F
DOI：
10.1080/02652030701598694
发表时间：
2008-05-01
影响因子：
2.9
作者：
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通讯作者：
Phillips, T. D.
影响因子：
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作者：
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通讯作者：
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