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Vol. 24, Art. 35 (pp. 461-472)    |    2023       

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Comparative study of the toxic profile of tyrosine kinase inhibitors and traditional anticancer drugs in an experiment

Savateeva-Lubimova T.N., Sivak K.V., Aleksandrov A.G., Stosman K.I., Kazakova S.B.

Federal State Budgetary Institution «Smorodintsev Research institute of influenza» Ministry of Health of the Russian Federation

Brief summary

Liver injury, nephrotoxicity, and hematopoiesis inhibition are the most severe complications of traditional antitumor therapy, which necessitated the development of drugs that selectively affect specific molecular targets in malignant cells. Early identification of various types toxicity biomarkers during innovative antitumor agents usage can contribute to the timely detection and correction of side effects. In the experiment, the toxic profile of imatinib and gefitinib was studied in comparison with cyclophosphamide and methotrexate when administered intragastrically for 14 days at doses equivalent to one therapeutic dose for an adult and exceeding it by 10 times, taking into account the coefficients of dose transfer to rodents. The obtained results demonstrated that imatinib caused a dose-dependent increase in the activity of hepatocyte cytolysis enzymes, lymphopenia and thrombocytopenia, unlike gefitinib, which caused insignificant disorders of the liver and blood system only when used at a dose exceeding the therapeutic dose by 10 times. The widest range of side effects was observed, including indicators of hepatotoxicity, nephrotoxicity and hepatotoxicity, when using cyclophosphamide. The toxicity profile of methotrexate included indicators of hepatotoxicity and hematotoxicity.


Key words

imatinib; gefitinib; cyclophosphamide; methotrexate; toxicity; rats

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