The teratogenic effects of imatinib mesylate on rat fetuses

Publication date: Available online 11 May 2015 Source:Toxicology Reports Author(s): M.M. El Gendy , A.M. Kandil , M.A. Helal , F.M. Zahou 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 was served as a control group. The second and third groups were orally administered imatinib at doses of 36mg/kg body weight or 54mg/kg b.wt on gestation days (SDs) 6 through 13 or SDs 13 through 19, respectively .All animals were sacrificed on the twentieth 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 54mg/kg b.wt and causes direct maternal or developmental toxicity.
Source: Toxicology Reports - Category: Toxicology Source Type: research