HEPATOTOXICITY ASSOCIATED WITH IMATINIB MESYLATE IN MATERNAL AND FETAL RATS

M. M. EL GENDY, A. M. KANDIL, M. A. HELAL* AND F. M. ZAHOU; Helal, Mona;

Abstract


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.


Other data

Title HEPATOTOXICITY ASSOCIATED WITH IMATINIB MESYLATE IN MATERNAL AND FETAL RATS
Authors M. M. EL GENDY, A. M. KANDIL, M. A. HELAL* AND F. M. ZAHOU ; Helal, Mona 
Keywords Imatinib mesylate; pregnancy; fetuses; liver; DNA fragmentation; histology.
Issue Date 2015
Publisher International Knowledge Press www.ikpress.org
Journal Journal of Biology and Nature 4(3): 141-151 
ISSN 2395-5384

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