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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doaj-9f805bfb9c0f42ffaab165ac84c92ba72020-11-25T03:47:23ZengScientific Medical Association of MoldovaThe Moldovan Medical Journal2537-63732537-63812020-10-01634434810.5281/zenodo.4016812The role of endothelin-1 in the doxorubicin cardiotoxicityLilia Tacu0https://orcid.org/0000-0003-0940-2527Department of Pathophysiology and Clinical Pathophysiology, Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, the Republic of MoldovaBackground: 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.http://moldmedjournal.md/wp-content/uploads/2020/09/moldovan-med-j-2020-63-4-tacu-full-text.pdfdoxorubicin cardiomyopathyendothelin-1coronary flowheart reactivity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lilia Tacu |
spellingShingle |
Lilia Tacu The role of endothelin-1 in the doxorubicin cardiotoxicity The Moldovan Medical Journal doxorubicin cardiomyopathy endothelin-1 coronary flow heart reactivity |
author_facet |
Lilia Tacu |
author_sort |
Lilia Tacu |
title |
The role of endothelin-1 in the doxorubicin cardiotoxicity |
title_short |
The role of endothelin-1 in the doxorubicin cardiotoxicity |
title_full |
The role of endothelin-1 in the doxorubicin cardiotoxicity |
title_fullStr |
The role of endothelin-1 in the doxorubicin cardiotoxicity |
title_full_unstemmed |
The role of endothelin-1 in the doxorubicin cardiotoxicity |
title_sort |
role of endothelin-1 in the doxorubicin cardiotoxicity |
publisher |
Scientific Medical Association of Moldova |
series |
The Moldovan Medical Journal |
issn |
2537-6373 2537-6381 |
publishDate |
2020-10-01 |
description |
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. |
topic |
doxorubicin cardiomyopathy endothelin-1 coronary flow heart reactivity |
url |
http://moldmedjournal.md/wp-content/uploads/2020/09/moldovan-med-j-2020-63-4-tacu-full-text.pdf |
work_keys_str_mv |
AT liliatacu theroleofendothelin1inthedoxorubicincardiotoxicity AT liliatacu roleofendothelin1inthedoxorubicincardiotoxicity |
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