Morphological assessment of changes in internal organs of rats with introduction of targeted drug “Sutent” in experiment

Objective. To establish in the experiment the changes in histological structure of the internal organs and blood indices in laboratory rats with intragastric introduction of the drug Sutent® in the doses of 7 mg/kg and 35 mg/kg of the weight.

Materials and methods. The study was conducted on 48 breedless white rats divided into the following groups: groups 1 and 4 – received cytotoxic drug Sutent® in the dose of 7 mg/kg (therapeutic dose), groups 2 and 5 – Sutent® in the dose of 35 mg/kg (fivefold exceeding the therapeutic dose), groups 3 and 6 – the control groups. In groups 1, 2, 3 animal were killed 30 days after the onset of the experiment, in groups 4, 5, 6 – two weeks after the drug withdrawal. Every day during 30 days, the experimental groups were introduced the intragastric drug Sutent® in the form of aqueous suspension in the purified water; in the control group the rats received the purified water in the equivalent volume. The histological preparations of organs stained with hematoxylin and eosin as well as the hematological indices of blood were investigated.

Results. The development of hypochromic anemia, thrombocytopenia and granulocytopenia in the was identified. While studying the histological structure of organs, in all experimental groups there was detected a disturbed circulation in the form of venous hyperemia and blood stasis in the capillaries, the development hemorrhages in the lung, liver, kidneys, adrenal glands, pancreas, gastric and esophageal mucosa. In the liver, pancreas and adrenal glands, dystrophic changes in the cells and necrosis foci were observed. In group 2, affection of the cerebral cortex nerve cells, heart cardiomyocytes, thyroid cells, acute duodenitis with formation of microabscesses was established.

Conclusions. Introduction of Sutent® in the dose of 35 mg/kg, compared with the dose of 7 mg/kg, caused a more expressed hematological, hepatological, cardiological and neurological toxicity, more obvious lesion of endocrine organs; it also contributed to the development of associated secondary infection and acute duodenitis.