Studies in Succession of Captopril and Darbepoetin Alfa Attenuate Radiation-Induced-Endothelial Dysfunction
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Author:
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KAREN SAROYAN, MICHAIL V. SYTNIK, EDUARD S. MILLER, OLESYA A. PUCHENKOVA , VLADISLAV O. SOLDATOV, ANASTASIA S. GASHEVSKAYA, ELENA B. ARTYUSHKOVA, OLEG S. GUDYREV
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Abstract:
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Background: Captopril and darbepoetin are drugs with high radioprotective potential.
Materials and Methods: The experiments were performed on male 55 Wistar rats. Rats were divided into 5 equal groups: 1) Intact; 2) Control; 3) Captopril (15 mg/kg); 4) Darbepoetin alfa (5000 U/kg); 5) Captopril (15 mg/kg) + Darbepoetin alfa (5000 U/kg). To simulate the RIED animals were subjected to ionizing-radiation injury at 500 roentgens with an exposure of 20 seconds. To evaluate the endothelial dysfunction (ED) level all rats were subjected to coefficient of ED (CED) calculation and determination of blood pressure (BP) and eNOS expression level, as well as diameter of cardiomycytes and carotid intima/media ratio.
Results and Discussion: According to the degree of therapeutic effect, the used treatment schemes can be arranged in the following sequence (to reduce the effect): Captopril + Darbepoetin alfa > Captopril > Darbepoetin alfa. In this case, the combination of captopril 15 mg/kg i.p. + darbepoetin-alpha in a dose of 5000 U/kg i.p. brought the values of functional and laboratory tests to a group of intact animals.
Conclusion: The combination of captopril + darbepoetin alfa has a high radio- and endothelioprotective potential and can be recommended for further preclinical and clinical studies.
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Keyword:
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captopril, darbepoetin alfa, dysfunction.
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EOI:
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DOI:
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https://doi.org/10.31838/ijpr/2019.11.04.0325
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