Histological changes of the rat liver after administration of imatinib mesylate:an experimental study

Objectives: This study aims to determine the histological changes of the liver of rats after administration of a low dose or a clinically relevant high dose of Imatinib mesylate for one month in comparison to control ones. Study setting and design: This experimental study was performed over a period of four months starting from the 10 march 2013 to the 10 July 2013 and was conducted on male Albino rats purchased from Animal Houses of both Mosul Medical College, and Veterinary College, University of Mosul, Mosul, Northern Iraq. Methods: The first experiment includes4045 days aged rats who administered orally daily dose of 75mg/Kg of imatinib mesylate (Glivec®; Novartis) purchased from IBN-SENA Teaching Hospital , Mosul and bought from some private pharmacies for 30 days with age matched control who administered distilled water. The second experiment includes 4045 days aged rats who administered daily dose of 200mg/Kg orally)with age matched control who administered distilled water . Liver of rats from each experimental group were obtained. The tissues were embedded in paraffin and stained with hematoxylin-eosin and periodic acid schiff stain. Results: The histological examination of the liver tissues of groups receiving imatinib at doses of 75 mg/kg or 200mg/kg on daily for 30 days duration showed different degrees of various histological changes of damage when compared with the control group . Male rats administered with 75 mg/kg of imatinib resulted moderate degree of several histological changes. The most striking feature is disruption in radial arrangement around central vein, sinusoidal dilatation, and hepatocytes with eosinophilic cytoplasm. Perivenular inflammatory cells, accumulation of inflammatory cells. Loss of cellular outline , and loss of euchromatin of the hepatocytes .Light microscopic examination of sections obtained from liver tissues of groups receiving imatinib at dose of 200mg/kg revealed similar changes, however , these changes were more pronounced in comparison to those in low dose group. Conclusion: Imatinib causes hepatotoxicity even in low dose group (75mg/kg, however, it has a dose dependant effect but to some extent. Appropriate protective measures must be applied with anticancer treatment for improving liver function.