Imatinib (Imb) mesylate is fully approved for the treatment of patients with chronic myeloid leukaemia (CML) in chronic phase after failure of interferon- therapy in blast crisis and in accelerated phase. Cardiotoxicity is an important consideration in the evaluation of cancer chemotherapy, because chemotherapy-induced myocardial damage might be irreversible and lethal. The aim of this work is to evaluate the cardiotoxicity of Imatinib mesylate following repeated administration of different doses and periods in adult male rabbits. fifty four adult male rabbits were utilized and divided equally into 3 groups: control group (group I), low dose Imb group (group II); received orally Imatinib mesylate (50 mg/kg/day) for 4 weeks and high dose Imb group (group III); received orally Imatinib mesylate (100 mg/kg/day) for 4 weeks. Cardiotoxicity was evaluated by electrocardiograph (ECG), biochemical and histopathological examination. Specimens and samples were taken 2 and 4 weeks from the start of the experiment and 2 weeks after drug withdrawal. ECG revealed left ventricular contractile dysfunction and mild diastolic dysfunction. Imb treated groups resulted in significant increases (. 0.001) in serum creatine kinase isoenzyme (CK-MB), cardiac troponin T (cTnc T), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) activity levels. Cardiac tissue of rats treated with imatinib showed significantly increased cardiac MDA production level and significant decreased (. 0.001) glutathione peroxidase (GPx) activity level and Total nitrate/nitrite (Nox) content. Those changes were proportional increase with increase dose and time of Imb and irreversible after stoppage of drugs. Imatinib mesylate have significant cardiotoxicity that alarming oncologists to avoid medication errors with Imb either large dose or for long periods administration that may have resulted in fatalities. |
