An approach to the toxicity and toxicokinetics of aflatoxin B1 and ochratoxin A after simultaneous oral administration to fasted F344 rats
An approach to the toxicity and toxicokinetics of aflatoxin B1 and ochratoxin A after simultaneous oral administration to fasted F344 rats
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DOI：
10.1016/j.fct.2012.06.048
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发表时间：
2012-10-01
影响因子：
4.3
通讯作者：
Lopez de Cerain, A.
中科院分区：
文献类型：
--
作者：
Corcuera, L. A.;Vettorazzi, A.;Lopez de Cerain, A.
人类通过饮食接触到肝脏毒性的黄曲霉毒素B1(AFB1)和肾毒性的赭曲霉毒素A(OTA)。在本研究中，黄曲霉毒素F1(0.25 mg/kgbw)+OTA(0.5 mg/kgbw)单次口服给F344大鼠。在不同时间点采集血液、肝脏和肾脏进行真菌毒素定量、相对重量计算、临床生化和组织病理学分析。毒性参数表明黄曲霉毒素1对肝脏有急性毒性。对肾脏和免疫器官无明显毒性。AFB1和OTA的最大血药浓度(C-max)分别为10分钟和2小时。AFB1血浆浓度可反映真菌毒素的快速吸收/代谢，肝脏和肾脏AFB1浓度分别低于LOQ和LOD。OTA在血浆中的C-max为4326.2微克/L。在肾脏和肝脏中，C-max在8h达到峰值，两个器官在各个时间点的浓度非常接近，由于AFB1水平较低，无法评估OTA对AFB1动力学的影响。然而，AFB1似乎不影响OTA动力学，因为它的轮廓似乎非常类似于在类似条件下仅用OTA进行的动力学研究。(C)2012爱思唯尔有限公司。保留所有权利。
Humans are exposed to the hepatotoxic aflatoxin B1 (AFB1) and nephrotoxic ochratoxin A (OTA) through diet. However, kinetic and toxicological data after their co-administration are scarce.In this study, a single oral dose of AFB1 (0.25 mg/kg bw) + OTA (0.5 mg/kg bw) was administered to fasted F344 rats. Blood, liver and kidney were harvested at different timepoints for mycotoxins quantification, relative weight calculation, clinical biochemistry and histopathology analysis.Toxicity parameters pointed to acute toxicity in liver due to AFB1. No remarkable toxicity was observed in kidneys or immunological organs. Maximum observed concentrations in plasma (C-max) were at 10 min and 2 h for AFB1 and OTA, respectively. AFB1 plasma concentration could indicate a rapid absorption/metabolism of the mycotoxin; and AFB1 liver and kidney concentrations were lower than LOQ and LOD, respectively. For OTA, C-max was 4326.2 mu g/L in plasma. In kidney and liver C-max was reached at 8 h and concentrations were very similar between both organs at all timepoints.Due to the low levels of AFB1, the effect of OTA on AFB1 kinetics could not be assessed. However, AFB1 seems not to affect OTA kinetics, as its profile seems very similar to kinetic studies performed only with OTA in similar conditions. (C) 2012 Elsevier Ltd. All rights reserved.