Dextromethorphan Reduces Oxidative Stress and Inhibits Uremic Artery Calcification

Medial vascular calcification has emerged as a key factor contributing to cardiovascular mortality in patients with chronic kidney disease (CKD). Vascular smooth muscle cells (VSMCs) with osteogenic transdifferentiation play a role in vascular calcification. Nicotinamide adenine dinucleotide phospha...

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Autores principales:	En-Shao Liu, Nai-Ching Chen, Tzu-Ming Jao, Chien-Liang Chen
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	dextromethorphan smooth muscle cell arterial calcification Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/4eb960f8fe464f61b6384cfebf7bfc9f
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spelling	oai:doaj.org-article:4eb960f8fe464f61b6384cfebf7bfc9f2021-11-25T17:54:58ZDextromethorphan Reduces Oxidative Stress and Inhibits Uremic Artery Calcification10.3390/ijms2222122771422-00671661-6596https://doaj.org/article/4eb960f8fe464f61b6384cfebf7bfc9f2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12277https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Medial vascular calcification has emerged as a key factor contributing to cardiovascular mortality in patients with chronic kidney disease (CKD). Vascular smooth muscle cells (VSMCs) with osteogenic transdifferentiation play a role in vascular calcification. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors reduce reactive oxygen species (ROS) production and calcified-medium–induced calcification of VSMCs. This study investigates the effects of dextromethorphan (DXM), an NADPH oxidase inhibitor, on vascular calcification. We used in vitro and in vivo studies to evaluate the effect of DXM on artery changes in the presence of hyperphosphatemia. The anti-vascular calcification effect of DXM was tested in adenine-fed Wistar rats. High-phosphate medium induced ROS production and calcification of VSMCs. DXM significantly attenuated the increase in ROS production, the decrease in ATP, and mitochondria membrane potential during the calcified-medium–induced VSMC calcification process (<i>p</i> < 0.05). The protective effect of DXM in calcified-medium–induced VSMC calcification was not further increased by NADPH oxidase inhibitors, indicating that NADPH oxidase mediates the effect of DXM. Furthermore, DXM decreased aortic calcification in Wistar rats with CKD. Our results suggest that treatment with DXM can attenuate vascular oxidative stress and ameliorate vascular calcification.En-Shao LiuNai-Ching ChenTzu-Ming JaoChien-Liang ChenMDPI AGarticledextromethorphansmooth muscle cellarterial calcificationBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12277, p 12277 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	dextromethorphan smooth muscle cell arterial calcification Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	dextromethorphan smooth muscle cell arterial calcification Biology (General) QH301-705.5 Chemistry QD1-999 En-Shao Liu Nai-Ching Chen Tzu-Ming Jao Chien-Liang Chen Dextromethorphan Reduces Oxidative Stress and Inhibits Uremic Artery Calcification
description	Medial vascular calcification has emerged as a key factor contributing to cardiovascular mortality in patients with chronic kidney disease (CKD). Vascular smooth muscle cells (VSMCs) with osteogenic transdifferentiation play a role in vascular calcification. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors reduce reactive oxygen species (ROS) production and calcified-medium–induced calcification of VSMCs. This study investigates the effects of dextromethorphan (DXM), an NADPH oxidase inhibitor, on vascular calcification. We used in vitro and in vivo studies to evaluate the effect of DXM on artery changes in the presence of hyperphosphatemia. The anti-vascular calcification effect of DXM was tested in adenine-fed Wistar rats. High-phosphate medium induced ROS production and calcification of VSMCs. DXM significantly attenuated the increase in ROS production, the decrease in ATP, and mitochondria membrane potential during the calcified-medium–induced VSMC calcification process (<i>p</i> < 0.05). The protective effect of DXM in calcified-medium–induced VSMC calcification was not further increased by NADPH oxidase inhibitors, indicating that NADPH oxidase mediates the effect of DXM. Furthermore, DXM decreased aortic calcification in Wistar rats with CKD. Our results suggest that treatment with DXM can attenuate vascular oxidative stress and ameliorate vascular calcification.
format	article
author	En-Shao Liu Nai-Ching Chen Tzu-Ming Jao Chien-Liang Chen
author_facet	En-Shao Liu Nai-Ching Chen Tzu-Ming Jao Chien-Liang Chen
author_sort	En-Shao Liu
title	Dextromethorphan Reduces Oxidative Stress and Inhibits Uremic Artery Calcification
title_short	Dextromethorphan Reduces Oxidative Stress and Inhibits Uremic Artery Calcification
title_full	Dextromethorphan Reduces Oxidative Stress and Inhibits Uremic Artery Calcification
title_fullStr	Dextromethorphan Reduces Oxidative Stress and Inhibits Uremic Artery Calcification
title_full_unstemmed	Dextromethorphan Reduces Oxidative Stress and Inhibits Uremic Artery Calcification
title_sort	dextromethorphan reduces oxidative stress and inhibits uremic artery calcification
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/4eb960f8fe464f61b6384cfebf7bfc9f
work_keys_str_mv	AT enshaoliu dextromethorphanreducesoxidativestressandinhibitsuremicarterycalcification AT naichingchen dextromethorphanreducesoxidativestressandinhibitsuremicarterycalcification AT tzumingjao dextromethorphanreducesoxidativestressandinhibitsuremicarterycalcification AT chienliangchen dextromethorphanreducesoxidativestressandinhibitsuremicarterycalcification
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Dextromethorphan Reduces Oxidative Stress and Inhibits Uremic Artery Calcification

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