Oral toxicity and pharmacokinetic studies of SHetA2, a new chemopreventive agent, in rats and dogs
Oral toxicity and pharmacokinetic studies of SHetA2, a new chemopreventive agent, in rats and dogs
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DOI：
10.3109/01480545.2012.710632
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发表时间：
2013-07-01
影响因子：
2.6
通讯作者：
Lyubimov, Alexander V.
中科院分区：
文献类型：
--
作者：
Kabirov, Kasim K.;Kapetanovic, Izet M.;Lyubimov, Alexander V.
SHetA 2是一种杂芳维A酸类化合物，其显示出选择性抑制癌细胞生长和诱导细胞凋亡而不激活核视黄酸受体。在大鼠研究中，以0、100、500和2，000 mg/kg/天剂量经口灌胃给予溶于1%甲基纤维素水溶液/0.2%吐温80中的SHetA 2，持续28天。高剂量给药诱导雄性大鼠活动减少、体重增加和摄食量减少以及器官重量变化。大鼠血浆中SHetA 2的主要代谢产物为单羟基SHetA 2，经口和静脉给药后，其代谢产物显著高于母体化合物。药代动力学分析显示极低（
SHetA2 is a heteroarotinoid that has shown selective inhibition of cancer cell growth and an induction of apoptosis without activation of nuclear retinoic acid receptors. In the rat study, SHetA2 was administered in 1% aqueous methylcellulose/0.2% Tween 80 by oral gavage at 0, 100, 500, and 2,000 mg/kg/day for 28 days. The high-dose administration induced decreased activity in male rats, decreased body-weight gains and food consumption, and changes in organ weights. The major metabolite of SHetA2 in rat plasma was monohydroxy SHetA2, which was considerably higher than the parent compound after oral and intravenous administration. Pharmacokinetic analysis showed extremely low (