Grape-Derived Polyphenols Prevent Doxorubicin-Induced Blunted EDH-Mediated Relaxations in the Rat Mesenteric Artery: Role of ROS and Angiotensin II
This study determined whether doxorubicin, an anticancer agent, impairs endothelium-dependent relaxations mediated by nitric oxide (NO) and endothelium-derived hyperpolarization (EDH) in the mesenteric artery and, if so, the mechanism underlying the protective effect of red wine polyphenols (RWPs),...
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doaj-688014ec1d1e4172b2be8066a8c6e2d72020-11-24T23:39:25ZengHindawi LimitedEvidence-Based Complementary and Alternative Medicine1741-427X1741-42882013-01-01201310.1155/2013/516017516017Grape-Derived Polyphenols Prevent Doxorubicin-Induced Blunted EDH-Mediated Relaxations in the Rat Mesenteric Artery: Role of ROS and Angiotensin IINoureddine Idris-Khodja0Paola Di Marco1Mona Farhat2Bernard Geny3Valérie B. Schini-Kerth4UMR CNRS 7213, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, 74 Route du Rhin, BP 60024, 67401 Illkirch, FranceInstitut de Physiologie, Faculté de Médecine, EA 3072, 11 Rue Humann, 67000 Strasbourg, FranceUMR CNRS 7213, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, 74 Route du Rhin, BP 60024, 67401 Illkirch, FranceInstitut de Physiologie, Faculté de Médecine, EA 3072, 11 Rue Humann, 67000 Strasbourg, FranceUMR CNRS 7213, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, 74 Route du Rhin, BP 60024, 67401 Illkirch, FranceThis study determined whether doxorubicin, an anticancer agent, impairs endothelium-dependent relaxations mediated by nitric oxide (NO) and endothelium-derived hyperpolarization (EDH) in the mesenteric artery and, if so, the mechanism underlying the protective effect of red wine polyphenols (RWPs), a rich natural source of antioxidants. Male Wistar rats were assigned into 4 groups: control, RWPs, doxorubicin, and doxorubicin + RWPs. Vascular reactivity was assessed in organ chambers; the vascular formation of reactive oxygen species (ROS) using dihydroethidine and the expression levels of small and intermediate conductance calcium-activated potassium channels (SKCa, IKCa) and connexin 40 (Cx40), which are involved in EDH-type relaxations, endothelial NO synthase (eNOS), angiotensin II, and AT1 receptors by immunofluorescence. The doxorubicin treatment impaired EDH-mediated relaxations, whereas those mediated by NO were minimally affected. This effect was associated with reduced expression levels of SKCa, IKCa, and Cx40, increased expression levels of eNOS, angiotensin II, and AT1 receptors, and formation of ROS in mesenteric arteries. RWPs prevented both the doxorubicin-induced blunted EDH-type relaxations and the increased vascular oxidative stress, and they improved the expression levels of target proteins. These findings suggest that polyphenol-rich natural products might be of interest in the management of doxorubicin-induced vascular injury possibly by improving the vascular angiotensin system.http://dx.doi.org/10.1155/2013/516017 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Noureddine Idris-Khodja Paola Di Marco Mona Farhat Bernard Geny Valérie B. Schini-Kerth |
spellingShingle |
Noureddine Idris-Khodja Paola Di Marco Mona Farhat Bernard Geny Valérie B. Schini-Kerth Grape-Derived Polyphenols Prevent Doxorubicin-Induced Blunted EDH-Mediated Relaxations in the Rat Mesenteric Artery: Role of ROS and Angiotensin II Evidence-Based Complementary and Alternative Medicine |
author_facet |
Noureddine Idris-Khodja Paola Di Marco Mona Farhat Bernard Geny Valérie B. Schini-Kerth |
author_sort |
Noureddine Idris-Khodja |
title |
Grape-Derived Polyphenols Prevent Doxorubicin-Induced Blunted EDH-Mediated Relaxations in the Rat Mesenteric Artery: Role of ROS and Angiotensin II |
title_short |
Grape-Derived Polyphenols Prevent Doxorubicin-Induced Blunted EDH-Mediated Relaxations in the Rat Mesenteric Artery: Role of ROS and Angiotensin II |
title_full |
Grape-Derived Polyphenols Prevent Doxorubicin-Induced Blunted EDH-Mediated Relaxations in the Rat Mesenteric Artery: Role of ROS and Angiotensin II |
title_fullStr |
Grape-Derived Polyphenols Prevent Doxorubicin-Induced Blunted EDH-Mediated Relaxations in the Rat Mesenteric Artery: Role of ROS and Angiotensin II |
title_full_unstemmed |
Grape-Derived Polyphenols Prevent Doxorubicin-Induced Blunted EDH-Mediated Relaxations in the Rat Mesenteric Artery: Role of ROS and Angiotensin II |
title_sort |
grape-derived polyphenols prevent doxorubicin-induced blunted edh-mediated relaxations in the rat mesenteric artery: role of ros and angiotensin ii |
publisher |
Hindawi Limited |
series |
Evidence-Based Complementary and Alternative Medicine |
issn |
1741-427X 1741-4288 |
publishDate |
2013-01-01 |
description |
This study determined whether doxorubicin, an anticancer agent, impairs endothelium-dependent relaxations mediated by nitric oxide (NO) and endothelium-derived hyperpolarization (EDH) in the mesenteric artery and, if so, the mechanism underlying the protective effect of red wine polyphenols (RWPs), a rich natural source of antioxidants. Male Wistar rats were assigned into 4 groups: control, RWPs, doxorubicin, and doxorubicin + RWPs. Vascular reactivity was assessed in organ chambers; the vascular formation of reactive oxygen species (ROS) using dihydroethidine and the expression levels of small and intermediate conductance calcium-activated potassium channels (SKCa, IKCa) and connexin 40 (Cx40), which are involved in EDH-type relaxations, endothelial NO synthase (eNOS), angiotensin II, and AT1 receptors by immunofluorescence. The doxorubicin treatment impaired EDH-mediated relaxations, whereas those mediated by NO were minimally affected. This effect was associated with reduced expression levels of SKCa, IKCa, and Cx40, increased expression levels of eNOS, angiotensin II, and AT1 receptors, and formation of ROS in mesenteric arteries. RWPs prevented both the doxorubicin-induced blunted EDH-type relaxations and the increased vascular oxidative stress, and they improved the expression levels of target proteins. These findings suggest that polyphenol-rich natural products might be of interest in the management of doxorubicin-induced vascular injury possibly by improving the vascular angiotensin system. |
url |
http://dx.doi.org/10.1155/2013/516017 |
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