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Combretastatin A4 disodium phosphate-induced myocardial injury
Histopathological and electrocardiographic features of myocardial lesions induced by combretastatin A4 disodium phosphate (CA4DP) were evaluated, and the relation between myocardial lesions and vascular changes and the direct toxic effect of CA4DP on cardiomyocytes were discussed. We induced myocard...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Japanese Society of Toxicologic Pathology
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963615/ https://www.ncbi.nlm.nih.gov/pubmed/27559241 http://dx.doi.org/10.1293/tox.2016-0012 |
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author | Tochinai, Ryota Nagata, Yuriko Ando, Minoru Hata, Chie Suzuki, Tomo Asakawa, Naoyuki Yoshizawa, Kazuhiko Uchida, Kazumi Kado, Shoichi Kobayashi, Toshihide Kaneko, Kimiyuki Kuwahara, Masayoshi |
author_facet | Tochinai, Ryota Nagata, Yuriko Ando, Minoru Hata, Chie Suzuki, Tomo Asakawa, Naoyuki Yoshizawa, Kazuhiko Uchida, Kazumi Kado, Shoichi Kobayashi, Toshihide Kaneko, Kimiyuki Kuwahara, Masayoshi |
author_sort | Tochinai, Ryota |
collection | PubMed |
description | Histopathological and electrocardiographic features of myocardial lesions induced by combretastatin A4 disodium phosphate (CA4DP) were evaluated, and the relation between myocardial lesions and vascular changes and the direct toxic effect of CA4DP on cardiomyocytes were discussed. We induced myocardial lesions by administration of CA4DP to rats and evaluated myocardial damage by histopathologic examination and electrocardiography. We evaluated blood pressure (BP) of CA4DP-treated rats and effects of CA4DP on cellular impedance-based contractility of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). The results revealed multifocal myocardial necrosis with a predilection for the interventricular septum and subendocardial regions of the apex of the left ventricular wall, injury of capillaries, morphological change of the ST junction, and QT interval prolongation. The histopathological profile of myocardial lesions suggested that CA4DP induced a lack of myocardial blood flow. CA4DP increased the diastolic BP and showed direct effects on hiPS-CMs. These results suggest that CA4DP induces dysfunction of small arteries and capillaries and has direct toxicity in cardiomyocytes. Therefore, it is thought that CA4DP induced capillary and myocardial injury due to collapse of the microcirculation in the myocardium. Moreover, the direct toxic effect of CA4DP on cardiomyocytes induced myocardial lesions in a coordinated manner. |
format | Online Article Text |
id | pubmed-4963615 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Japanese Society of Toxicologic Pathology |
record_format | MEDLINE/PubMed |
spelling | pubmed-49636152016-08-24 Combretastatin A4 disodium phosphate-induced myocardial injury Tochinai, Ryota Nagata, Yuriko Ando, Minoru Hata, Chie Suzuki, Tomo Asakawa, Naoyuki Yoshizawa, Kazuhiko Uchida, Kazumi Kado, Shoichi Kobayashi, Toshihide Kaneko, Kimiyuki Kuwahara, Masayoshi J Toxicol Pathol Original Article Histopathological and electrocardiographic features of myocardial lesions induced by combretastatin A4 disodium phosphate (CA4DP) were evaluated, and the relation between myocardial lesions and vascular changes and the direct toxic effect of CA4DP on cardiomyocytes were discussed. We induced myocardial lesions by administration of CA4DP to rats and evaluated myocardial damage by histopathologic examination and electrocardiography. We evaluated blood pressure (BP) of CA4DP-treated rats and effects of CA4DP on cellular impedance-based contractility of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). The results revealed multifocal myocardial necrosis with a predilection for the interventricular septum and subendocardial regions of the apex of the left ventricular wall, injury of capillaries, morphological change of the ST junction, and QT interval prolongation. The histopathological profile of myocardial lesions suggested that CA4DP induced a lack of myocardial blood flow. CA4DP increased the diastolic BP and showed direct effects on hiPS-CMs. These results suggest that CA4DP induces dysfunction of small arteries and capillaries and has direct toxicity in cardiomyocytes. Therefore, it is thought that CA4DP induced capillary and myocardial injury due to collapse of the microcirculation in the myocardium. Moreover, the direct toxic effect of CA4DP on cardiomyocytes induced myocardial lesions in a coordinated manner. Japanese Society of Toxicologic Pathology 2016-04-23 2016-07 /pmc/articles/PMC4963615/ /pubmed/27559241 http://dx.doi.org/10.1293/tox.2016-0012 Text en ©2016 The Japanese Society of Toxicologic Pathology http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. |
spellingShingle | Original Article Tochinai, Ryota Nagata, Yuriko Ando, Minoru Hata, Chie Suzuki, Tomo Asakawa, Naoyuki Yoshizawa, Kazuhiko Uchida, Kazumi Kado, Shoichi Kobayashi, Toshihide Kaneko, Kimiyuki Kuwahara, Masayoshi Combretastatin A4 disodium phosphate-induced myocardial injury |
title | Combretastatin A4 disodium phosphate-induced myocardial
injury |
title_full | Combretastatin A4 disodium phosphate-induced myocardial
injury |
title_fullStr | Combretastatin A4 disodium phosphate-induced myocardial
injury |
title_full_unstemmed | Combretastatin A4 disodium phosphate-induced myocardial
injury |
title_short | Combretastatin A4 disodium phosphate-induced myocardial
injury |
title_sort | combretastatin a4 disodium phosphate-induced myocardial
injury |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963615/ https://www.ncbi.nlm.nih.gov/pubmed/27559241 http://dx.doi.org/10.1293/tox.2016-0012 |
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