[ effects of chronic use of imatinib on wistar rat fetuses]

ABSTRACT

Imatinib mesylate selectively inhibits bcr/abl and other non-specific tyrosine kinases and represents a model of targeted therapy for chronic myeloid leukaemia [CML] as well as gastrointestinal stromal tumors [GIST]. This study was designed to evaluate effects of imatinib on pregnancy and development of fetus. In this experimental study, imatinib was administrated orally at doses of 7, 12, 22, 50 and 100 mg/kg/day and control groups received sterile water. The pregnant rats were subdivided into 2 groups. In group one, the pregnant rats were sacrificed on day 18 of gestation and the number alive and dead of foetuses were checked. The brain of fetuses were fixed in formalin and embedded in paraffin for histological studies. Selected slides were stained with hematoxylin and eosin [H and E]. In group two, the fetuses were allowed to become mature. The effect of drug on learning and memory were assessed by a passive avoidance method using shuttle box apparatus. Histological studies revealed no evidence of teratogenic effects of imatinib on development of frontal and parietal bones. Imatinib given in 100 mg/kg dose caused weight decrease [p<0.001] and increase mortality in fetuses [p<0.01]. Administration of imatinib in 7, 12, 22 and 50 mg/kg doses showed statistically significant reduction in learning and memory of fetuses [p<0.05]. Imatinib can decrease development, learning and memory of fetuses. So, it is recommended that women treated with imatinib avoid becoming pregnant