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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MDPI AG
2021-11-01
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| 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 |
| collection | DOAJ |
| 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. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T05:25:33Z |
| publishDate | 2021-11-01 |
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| spelling | doaj.art-4eb960f8fe464f61b6384cfebf7bfc9f2023-11-22T23:39:49ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122221227710.3390/ijms222212277Dextromethorphan Reduces Oxidative Stress and Inhibits Uremic Artery CalcificationEn-Shao Liu0Nai-Ching Chen1Tzu-Ming Jao2Chien-Liang Chen3Division of Cardiology, Kaohsiung Veterans General Hospital, Kaohsiung 813779, TaiwanDepartment of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 813779, TaiwanDivisions of Medical Research, Kaohsiung Veterans General Hospital, Kaohsiung 813779, TaiwanInstitutes of Clinical Medicine, National Yang Ming Chiao Tung University, Hsinchu City 30010, TaiwanMedial 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.https://www.mdpi.com/1422-0067/22/22/12277dextromethorphansmooth muscle cellarterial calcification |
| spellingShingle | En-Shao Liu Nai-Ching Chen Tzu-Ming Jao Chien-Liang Chen Dextromethorphan Reduces Oxidative Stress and Inhibits Uremic Artery Calcification International Journal of Molecular Sciences dextromethorphan smooth muscle cell arterial 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 | dextromethorphan smooth muscle cell arterial calcification |
| url | https://www.mdpi.com/1422-0067/22/22/12277 |
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