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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: Liu, En-Shao, Chen, Nai-Ching, Jao, Tzu-Ming, Chen, Chien-Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623041/
https://www.ncbi.nlm.nih.gov/pubmed/34830159
http://dx.doi.org/10.3390/ijms222212277
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author Liu, En-Shao
Chen, Nai-Ching
Jao, Tzu-Ming
Chen, Chien-Liang
author_facet Liu, En-Shao
Chen, Nai-Ching
Jao, Tzu-Ming
Chen, Chien-Liang
author_sort Liu, En-Shao
collection PubMed
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 (p < 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.
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spelling pubmed-86230412021-11-27 Dextromethorphan Reduces Oxidative Stress and Inhibits Uremic Artery Calcification Liu, En-Shao Chen, Nai-Ching Jao, Tzu-Ming Chen, Chien-Liang Int J Mol Sci Article 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 (p < 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. MDPI 2021-11-13 /pmc/articles/PMC8623041/ /pubmed/34830159 http://dx.doi.org/10.3390/ijms222212277 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, En-Shao
Chen, Nai-Ching
Jao, Tzu-Ming
Chen, Chien-Liang
Dextromethorphan Reduces Oxidative Stress and Inhibits Uremic Artery Calcification
title 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_short Dextromethorphan Reduces Oxidative Stress and Inhibits Uremic Artery Calcification
title_sort dextromethorphan reduces oxidative stress and inhibits uremic artery calcification
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623041/
https://www.ncbi.nlm.nih.gov/pubmed/34830159
http://dx.doi.org/10.3390/ijms222212277
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