HEPATOTOXICITY ASSOCIATED WITH IMATINIB MESYLATE IN MATERNAL AND FETAL RATS

Imatinib mesylate is the first line treatment against chronic myelogenous leukaemia and gastrointestinal stromal tumors, its effects on liver of pregnant rats and their fetuses were evaluated in the present study. Female rats were divided into three main groups, the first group served as a control group. The second main group was divided into two subgroups and was orally administered low dose of imatinib mesylate (36 mg/kgbody weight) on gestation days (SDs) 6 through 13 and on SDs 13 through 19. The third main group was divided into two subgroups and was orally administered high dose of imatinib (54 mg/kg b.wt.) from 6th day to 13th day of gestation and from 13th day to 19th day of gestation. All animals were sacrificed on the 20th day of gestation. The results of the present work revealed that, serum alanin aminotransferase, aspartate aminotransferase, total bilirubin levels, direct bilirubin, alkaline phosphatase were increased significantly on SDs 6 through 13 or SDs 13 through 19 after treatment with imatinib, whereas serum albumin and total protein were decreased as compared to their respective control. Agarose gel electrophoresis showed marked increase (P = .001) in DNA damage in the form of smearing as well as ladder like fragmentation of the liver genomic DNA in pregnant rats and fetuses administered the two doses of imatinib. Liver tissues revealed different phases of histological changes represented by congestion of some blood vessels and sinusoids, hydropic and vacuolar degeneration accompanied with necrotic areas scattered in hepatic tissues. The present work concluded that, exposure to tyrosin kinase inhibitor (imatinib mesylate) at a dose 54 mg/kg b.wt. during pregnancy has hepatic adverse effects extend to certain biochemical, histological and molecular parameters in maternal and fetal rats. The health risk was increased as the dose of exposure to the imatinib increased.