Molecular Markers Profile of Fibrosis in Rats Exposed to Different Doses of Doxorubicin

Abstract

Text of the abstract. The study is devoted to the investigate of the molecular markers profile of fibrosis when various doses of doxorubicin are administered to Wistar drain rats. The study was performed on 40 male Wistar rats weighing 260 ± 19 g. Animals were divided into 4 groups: control and three experimental groups with a certain frequency of administration (6 times in two days) and a certain dose of doxorubicin (5, 10, 15 mg/kg, intraperitoneally). At the end of the administration of the chemotherapy drug, the animals were observed for 2 months. To solve this aim, the hearts were taken from anesthetized animals for molecular and morphological studies. Histological, echocardiographic and molecular analyses revealed dose-dependent damaging changes in the left ventricular myocardium against the background of exposure to various doses of doxorubicin. The expression level of TGF-β did not differ from the control values 2 months after the end of administration of all cumulative doses of the chemotherapy drug. However, at this stage of the study, the preserved increased expression of type I, type II collagen, ET-1, FGF4 and TNF-α was characteristic of animals receiving the maximum cumulative dose of doxorubicin, which may reflect the incompleteness of the fibrous tissue formation process, as well as their active participation in the development of inflammatory processes with pronounced cardiotoxic damage against the background of exposure the chemotherapy drug. For animals receiving 10 mg/kg, there were no changes in these molecular markers of fibrosis compared to the control group, whereas in the group of animals with the minimum cumulative dose of the drug, a decrease in the expression of COL I, II type, ET-1, TNF-α and an increase in FGF4 levels were revealed.