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蒿甲醚在大鼠孕期不同阶段的发育毒性评价。

Evaluation of the developmental toxicity of artemether during different phases of rat pregnancy.

作者信息

El-Dakdoky M H

机构信息

Department of Zoology, Girls College for Arts, Science and Education, Ain Shams University, 1 Asmaa Fahmey St., Heliopolis, Cairo 11757, Egypt.

出版信息

Food Chem Toxicol. 2009 Jul;47(7):1437-41. doi: 10.1016/j.fct.2009.03.027. Epub 2009 Mar 28.

Abstract

The present investigation was performed to examine the effect of artemether on rat pregnancy and embryonic/fetal development during different phases of pregnancy. Artemether was administered orally to Wistar rats at doses 3.5 and 7 mg/kg during blastogenesis, organogenesis and fetal period. When administered during blastogenesis, the preimplantation loss, number of implantations, resorptions, living fetuses, external and skeletal examination did not differ from those of control, however the higher dose induced reduction in fetal body weight and caused pre-term delivery in 3 of 10 pregnant rats. During organogenesis complete fetal resorption was observed in all dams treated with the higher dose, while in the lower dose 32% of implants were resorbed and live fetuses showed decreased fetal weight with low incidence of skeletal retardation. Artemether did not adversely affect prenatal development in rats treated during the fetal period although the higher dose level induced reduction in fetal body weight. In conclusion, no evidence of maternal toxicity, artemether was embryolethal at 3.5 and 7 mg/kg when dosed during organogenesis, the surviving fetuses showed fetal growth retardation without incidence of malformations, treatment during blastogenesis and fetal period had no lethal or teratogenic effect although the mean fetal body weight was significantly lower than control.

摘要

本研究旨在考察蒿甲醚对大鼠孕期不同阶段妊娠及胚胎/胎儿发育的影响。在大鼠胚胎发生期、器官形成期和胎儿期,分别以3.5mg/kg和7mg/kg的剂量对Wistar大鼠口服给予蒿甲醚。在胚胎发生期给药时,着床前损失、着床数、吸收胎数、活胎数、外观及骨骼检查结果与对照组相比无差异,但较高剂量导致胎鼠体重降低,并使10只孕鼠中的3只早产。在器官形成期,高剂量组所有母鼠的胚胎均完全吸收,低剂量组32%的着床胚胎被吸收,活胎体重降低,骨骼发育迟缓发生率较低。在胎儿期给药时,蒿甲醚对大鼠产前发育无不良影响,尽管较高剂量组胎鼠体重降低。总之,没有母体毒性的证据,在器官形成期给予3.5mg/kg和7mg/kg剂量的蒿甲醚具有胚胎致死性,存活胎儿表现为生长迟缓但无畸形发生,在胚胎发生期和胎儿期给药虽平均胎鼠体重显著低于对照组,但无致死或致畸作用。

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