Carbamylated darbepoetin in combination with ethoxydol attenuates doxorubicin-induced cardiomyopathy in rats


Introduction: Doxorubicin is the drug of choice in the treatment of many malignant neoplasms, but its use is limited due to the risk of developing severe cardiomyopathy. This problem necessitates the prevention, early diagnosis and treatment of cardiomyopathy.
Material and Methods: The study was conducted on 80 male white Wistar rats, which were administered the following drugs during the experiment: doxorubicin (Teva) at a dose of 20 mg /kg, ethoxydol at a dose of 50 mg/kg, carbamylated darbepoetin at a dose of 50 mg/kg. The hearts of the rats were perfused in the installation of a Langendorf-isolated heart. All rats were recorded contractility indicators: maximum intraventricular pressure (IVP) (mm Hg), minimum IVP (mm Hg), average IVP (mm Hg), pulse IVP (mm. Hg), heart rate (HR, beats/min), maximum myocardial contraction rate (+ dP/dtmax, mm Hg/sec), maximum myocardial relaxation rate (-dP/dtmax, mm Hg/sec.), a test was performed with high-frequency stimulation. To assess the reserve capacity of the myocardium, we used the Tension-Time Index (tTTI) test of the “voltage over time” index.
Results: When used as a cardioprotector of ethoxydol at a dose of 50 mg/kg, a decrease in the toxic effect of DR and an improvement in performance by 14.8% compared with the group of DR. The degree of change in contractility indicators compared with the positive control group was 48.7%. As a result of CDEPO at a dose of 50 mg/kg, there is also a positive trend in the change in myocardial contractility, but to a lesser extent than in ethoxydol. The difference in performance compared with the DR group is 8.6%. The greatest cardioprotective effect was achieved by the introduction of a combination of DR and CDEPO. The increase in contractility compared with the doxorubicin group was 23.9%. The severity of changes in contractility indicators decreased to 38.5% compared with the positive control group. This trend in the dynamics of myocardial contractility indices can be traced both in the conditions of perfusion with norcalcium and hypercalcium solutions.
Conclusion: The most pronounced cardioprotective effect on the model of doxorubicin cardiomyopathy is determined by using a combination of carbamylated darbepoetin at a dose of 50 mkg/kg with ethoxydol at a dose of 50 mg/kg.


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