The teratogenic effects of imatinib mesylate on rat fetuses

Abstract

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.

Keywords

• Imatinib
• Pregnant rat
• Fetuses
• Congenital deformities
• Skeleton