The role of endothelin-1 in the doxorubicin cardiotoxicity
Background: The cardiotoxicity of doxorubicin (Dx), an antineoplastic drug, is imposed by the development of cardiomyopathy and heart failure. The expression of endothelin-1 (ET-1) in myocardium under the action of Dx, directly correlates with the degree of cardiac dysfunction, mediated by endothe...
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| Format: | Article |
| Language: | English |
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Scientific Medical Association of Moldova
2020-10-01
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| Series: | The Moldovan Medical Journal |
| Subjects: | |
| Online Access: | http://moldmedjournal.md/wp-content/uploads/2020/09/moldovan-med-j-2020-63-4-tacu-full-text.pdf |
| Summary: | Background: The cardiotoxicity of doxorubicin (Dx), an antineoplastic drug, is imposed by the development of cardiomyopathy and heart failure.
The expression of endothelin-1 (ET-1) in myocardium under the action of Dx, directly correlates with the degree of cardiac dysfunction, mediated by
endothelin A (ETA) receptor.
Material and methods: For prospective randomized study 2 groups of white rats (experimental group n=9, control group n=9) were used. During 2
weeks in the control group was administrated Dx (i/p, 4mg/kg in one dose, twice/week), cumulative dose – 16 mg/kg. The ET-1 effects were estimated
at its peak action in concentration 10-7 M (mol), reproduced after 30 sec of endothelin stimulation.
Results: The functional parameters of isolated heart perfused in physiologic regime and in condition of volume and resistance overload under the ET-1
action in the group with Dx compared with the control one, were reduced considerably, namely: cardiac output (CO); left ventricle systolic pressure
(LVSP); left ventricle end-diastolic pressure (LVEDP).
Conclusions: Under the ET-1 action on the isolated heart perfused in physiologic regime in the group with Dx – the LVSP and CO were reduced determining
negative inotropic effect. At the volume overload test, under the ET-1 action, the diastolic impairment was more evident in the group with Dx, due to
increased LVEDP. At the resistance overload test under the ET-1 action, the CO was reduced indicating the depreciation of myocardial contraction capacity. |
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| ISSN: | 2537-6373 2537-6381 |