Background
Imatinib mesylate (Gleevec) is a small-molecule inhibitor of the fusion protein BCR-ABL, the causal agent in chronic myeloid leukemia. It is widely used for the treatment of chronic myeloid leukaemia and gastrointestinal stromal tumors.
Aim of the work
This work was conducted to evaluate the cardiotoxicity of imatinib in adult male rabbits.
Material and Methods
In this study 27 adult male rabbits were utilized and divided equally into 3 groups: control group (group I), low dose imatinib group (group II) ); received orally imatinib mesylate (18 mg/kg/day) for 4 weeks and high dose imatinib group (group III) ); received orally imatinib mesylate (36 mg/kg/day) for 4 weeks. Left ventricular heart specimens were taken 2, 4 and 6 weeks from the start of the experiment (the 6 week sample was considered as a withdrawal sample) and sections were prepared for LM examination (H&E, Masson's trichrome and immunohistochemical detection of caspase-3) and EM examination.
Results
The results revealed that low therapeutic dose of imatinib mesylate (IM) induced minimal cardiac myocytes toxicity (mild cytoplasmic vacuolization, weakly expressed caspase-3 and slight mitochondrial swelling) only in the 4th week sections that disappeared after stoppage of the drug (6th week sections). High therapeutic dose of IM induced moderate cytoplasmic vacuolization, pyknosis of some cardiac myocytes, moderately expressed caspase-3 and mitochondrial swelling with disruption of the cristae in the 2nd week sections that became sever in the 4th week sections while the 6th week sections (withdrawal sample) showed moderate effect.
Conclusion
It could be concluded that, in spite of imatinib is effective in treatment of chronic myeloid leukaemia, its high dose is cardiotoxic and should be avoided especially in cardiac patients.
Key Words: Imatinib – cardiac toxicity
|
