Journal: Journal of Pharmacy Research

Article Id: JPRS-P'Col-00001943
Title: Protective effects of incretin mimetics in cardiomyopathy induced by doxorubicin
Category: Pharmacology
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    Introduction: The results of experimental and clinical trials make it clear that incretin mimetics possess pleiotropic effects and demonstrate the value in terms of assessment of their potential opportunities as cardioprotectors. Research Tasks: The aim is to study the cardioprotective effects of exenatide and vildagliptin on the model of doxorubicin-induced cardiomyopathy. Materials and Methods: The experiments on the Langendorff isolated rat heart were dedicated to the study of cardioprotective activity of exenatide (10 mcg/kg/day) (“Byetta®,” Eli Lilly and Company, USA) and vildagliptin (0.2 mg/kg/day) (“Galvus®,” Novartis, Switzerland), on the contractile function of the isolated heart which was previously perfused with doxorubicin (20 mg/kg, intraperitoneally before 48 h). The evaluation of cardioprotective activity was based on the findings of the functional trial with high-frequency stimulation (480 bmp) in hypercalcemia (5 mmol) perfusion. The complex evaluation of the myocardial damage in the flowing perfusate from isolated hearts included the assessment of creatine phosphokinase muscle brain isoenzyme (CPK-MB) and lactic dehydrogenase (LDH). The activity of lipid peroxidation (LPO) was evaluated by measuring the content of malondialdehyde (MDA) and diethenoid conjugant (DC). Results: Exenatide (10 mcg/kg/day) and vildagliptin (0.2 mg/kg/day) demonstrate a cardioprotective effect on the model of doxorubicin-induced pathology, resulting in a decrease of diastolic dysfunction to 5.3 ± 0.1 units and 6.5 ± 0.2 units, respectively, compared to control 8.3 ± 0.1 units. The cardioprotective effect was confirmed by 27% and 19% decrease in the levels of CPK-MB marker damage, and by 11.8% and 9.6% decrease in LDH levels, respectively, in exenatide and vildagliptin series, compared to control. The cardioprotective effect was also confirmed by prevention of accumulation of LPO products of MDA and DC in the ventricular myocardium. Conclusion: Exenatide (10 mcg/kg/day) and vildagliptin (0.2 mg/kg/day) decrease diastolic dysfunction, resulting in the recovery of the contractile function of the heart, reduction of the “diastole defect” (StТТI), and the decrease in irreversible damages of cardiomyocytes.

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    Author(s) Name:

    Alla P. Tarasova1*, Tatyana G. Pokrovskaya1, Alexander V. Faitelson2, Yury A. Khoshchenko1, Alena S. Timokhina1, Alla S. Kotelnikova1, Anatoly V. Khavansky1

    Affiliation(s) Name:

    1Department of Pharmacology, Medical Institute, Belgorod State National Research University, Belgorod, Russia,
    2Department of Pharmacology, Kursk State Medical University, Kursk, Russia

    *Corresponding author: Alla P. Tarasova, Postgraduate Student, Department of Pharmacology, Medical Institute, Belgorod State National Research University, 85, Pobedy St., Belgorod, 308015, Russia.

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    Author:

    Alla P. Tarasova1*, Tatyana G. Pokrovskaya1, Alexander V. Faitelson2, Yury A. Khoshchenko1, Alena S. Timokhina1, Alla S. Kotelnikova1, Anatoly V. Khavansky1

    Title:Protective effects of incretin mimetics in cardiomyopathy induced by doxorubicin
    Journal:Journal of Pharmacy Research
    Vol(issue):11(12)
    Year:2017
    Page No: (1565-1569)
  • Experimental Methods Keywords

    Methodology:cardioprotective activity
    Research Materials:Doxorubicin,Vildagliptin,Exenatide

Keywords

Doxorubicin-induced cardiomyopathy Exenatide Incretin mimetics Isolated rat heart Vildagliptin

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