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尿牛磺酸作为黄曲霉毒素B1诱导肝毒性的非侵入性标志物:成功与失败

Urinary taurine as a non-invasive marker of aflatoxin B1-induced hepatotoxicity: success and failure.

作者信息

Maxuitenko Y Y, North W G, Roebuck B D

机构信息

Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03755, USA.

出版信息

Toxicology. 1997 Mar 28;118(2-3):159-69. doi: 10.1016/s0300-483x(96)03610-4.

Abstract

The usefulness of urinary taurine as a non-invasive measure of hepatotoxicity of aflatoxin B1 (AFB1) was evaluated: changes in urinary taurine were characterized in a dose-response, acute toxicity experiment and in two sub-chronic, low dose exposure experiments. Urine of young, male, F344 rats was collected for 4 days prior to, and for 3 days after, the treatment with AFB1. Rats received a single p.o. dose of 0, 0.25, 0.5, 1, 2 or 3 mg AFB1/kg body wt. A transient increase in urinary taurine was noted with doses of 1, 2 or 3 mg AFB1/kg. In two sub-chronic exposure experiments, rats were gavaged with 25 microg AFB1/day for 5 successive days per week for 1 or 2 weeks (approximately 0.25 mg/kg/day). In the first experiment, only a transient increase in urinary taurine during 5 successive doses of AFB1 was observed, while in the second experiment, urinary taurine rose continuously during the 2 weeks of the AFB1 treatment. An explanation for these differing results is not obvious. Urinary taurine appeared to be a useful, non-invasive marker when hepatotoxicity was extensive. Unfortunately, at the low doses of AFB1 (0.25-0.5 mg/kg) as used in carcinogenesis experiments (10 doses of 25 microg/rat), urinary taurine appeared to be an insensitive measure of hepatic damage.

摘要

评估了尿牛磺酸作为黄曲霉毒素B1(AFB1)肝毒性非侵入性指标的实用性:在剂量反应急性毒性实验以及两个亚慢性低剂量暴露实验中,对尿牛磺酸的变化进行了表征。在给予AFB1治疗前4天和治疗后3天收集年轻雄性F344大鼠的尿液。大鼠经口给予0、0.25、0.5、1、2或3mg AFB1/kg体重的单次剂量。在给予1、2或3mg AFB1/kg剂量时,观察到尿牛磺酸短暂增加。在两个亚慢性暴露实验中,大鼠每周连续5天给予25μg AFB1灌胃,持续1或2周(约0.25mg/kg/天)。在第一个实验中,仅观察到连续5次给予AFB1期间尿牛磺酸短暂增加,而在第二个实验中,在AFB1治疗的2周内尿牛磺酸持续上升。这些不同结果的解释并不明显。当肝毒性广泛时,尿牛磺酸似乎是一个有用的非侵入性标志物。不幸的是,在致癌实验中使用的低剂量AFB1(0.25 - 0.5mg/kg)(每只大鼠10次给予25μg)时,尿牛磺酸似乎是肝脏损伤的不敏感指标。

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