El Gendy M M, Kandil A M, Helal M A, Zahou F M
Department of Zoology, Faculty of Women for Arts, Science & Education, Ain Shams University, Cairo, Egypt.
National Organization for Drug Control and Research, Giza, Cairo, Egypt.
Toxicol Rep. 2015 May 11;2:654-663. doi: 10.1016/j.toxrep.2015.05.001. eCollection 2015.
Imatinib mesylate, a selective tyrosine kinase inhibitor, is the first line treatment against chronic myelogenous leukemia and gastrointestinal stromal tumors. The aim of the present study is to investigate the effects of imatinib mesylate on the pregnant rats and their fetuses. Pregnant rats were divided into three groups; the first group served as a control group. The second and third groups were orally administered imatinib at doses of 36 mg/kg body weight or 54 mg/kg b.wt. on gestation days (SDs) 6 through 13 or SDs 13 through 19, respectively. All animals were sacrificed on the 20th day of gestation. Treatment with imatinib caused a reduction of maternal body weight gain, uterine and placental weights, increased rate of abortion and fetal resorptions. High dose of imatinib caused fetal congenital deformities represented in harelip, contraction of the fore limbs, and paralysis of the hind limbs, exencephaly, encephalocoele and distended abdominal wall, besides occurrence of wavy ribs and absence of other ribs in addition to skeletal growth retardation and lack of ossification of the most skeletal elements. The present work concluded that imatinib is teratogenic when given orally to pregnant rats at 54 mg/kg b.wt. and causes direct maternal or developmental toxicity.
甲磺酸伊马替尼是一种选择性酪氨酸激酶抑制剂，是治疗慢性粒细胞白血病和胃肠道间质瘤的一线药物。本研究旨在探讨甲磺酸伊马替尼对妊娠大鼠及其胎儿的影响。将妊娠大鼠分为三组；第一组作为对照组。第二组和第三组分别在妊娠第6至13天或第13至19天以36毫克/千克体重或54毫克/千克体重的剂量口服伊马替尼。所有动物在妊娠第20天处死。伊马替尼治疗导致母鼠体重增加、子宫和胎盘重量减轻，流产率和胎儿吸收增加。高剂量伊马替尼导致胎儿先天性畸形，表现为唇裂、前肢挛缩、后肢麻痹、无脑儿、脑膨出和腹壁膨出，此外还出现肋骨波浪状和其他肋骨缺失，以及骨骼生长迟缓，大多数骨骼元素缺乏骨化。本研究得出结论，当以54毫克/千克体重口服给予妊娠大鼠时，伊马替尼具有致畸性，并会导致母体直接毒性或发育毒性。
