Doxorubicin-associated Cardiomyopathy: New Approaches to Pharmacological Correction Using 3-(2,2,2-trimethylhydrazinium) Propionate Derivatives

Abstract

Introduction: The search for new compounds with cardioprotective activity amongst the 3-(2,2,2-trimethylhydrazinium) propionate derivatives looks promising.

Research objectives: to study cardioprotective effects of the 3-(2,2,2-trimethylhydrazinium) propionate derivatives.

Methods: The cardioprotective effect of the derivatives (nicotinate, 5-hydroxynicotinate) of 3-(2,2,2-trimethylhydrazinium) propionate) and reference medicine meldonium in the case of doxorubicin (DOX) (20 mg/kg, intraperitoneally for 48 hours) cardiomyopathy was evaluated by the results of a functional test with high-frequency stimulation (480 bpm).

To provide integral validation for the development of the simulated pathological processes, biochemical and morphological studies of the heart were carried out. For a biochemical evaluation of myocardial damage in the homogenisate, the isoenzyme creatinine kinase MB (CK-MB) and lactate dehydrogenase (LDH) were determined.

Results: The derivatives nicotinate and 5-hydroxynicotinate of 3-(2,2,2-trimethylhydrazinium) propionate) exert a cardioprotective effect on a doxorubicin pathology model, which is expressed in a decreased coefficient of diastolic dysfunction (StTTI) to the level of 5.8±0.1 ru and 4.6±0.2 ru in comparison with that in the control group 8.3±0.1 ru and reference medicine meldonium 6.5±0.1 ru, respectively.

The cardioprotective effect was confirmed by decreased levels of markers of damage to CK-MB and LDH and a decreased diameter of cardiomyocytes compared to those in the control group.

Conclusion: The derivatives of 3-(2,2,2-trimethylhydrazinium) propionate (nicotinate, 5-hydroxynicotinate) 3-(2,2,2-trimethylhydrazinium) propionate reduce diastolic dysfunction and irreversible damage to cardiomyocytes in case of doxorubicin-associated cardiomyopathy.