Cargando…
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...
Autores principales: | , , , |
---|---|
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 |
_version_ | 1784605836670140416 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8623041 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT liuenshao dextromethorphanreducesoxidativestressandinhibitsuremicarterycalcification AT chennaiching dextromethorphanreducesoxidativestressandinhibitsuremicarterycalcification AT jaotzuming dextromethorphanreducesoxidativestressandinhibitsuremicarterycalcification AT chenchienliang dextromethorphanreducesoxidativestressandinhibitsuremicarterycalcification |