PMID- 34830159
OWN - NLM
STAT- MEDLINE
DCOM- 20211220
LR  - 20211220
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 22
DP  - 2021 Nov 13
TI  - Dextromethorphan Reduces Oxidative Stress and Inhibits Uremic Artery 
      Calcification.
LID - 10.3390/ijms222212277 [doi]
LID - 12277
AB  - 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.
FAU - Liu, En-Shao
AU  - Liu ES
AD  - Division of Cardiology, Kaohsiung Veterans General Hospital, Kaohsiung 813779, 
      Taiwan.
AD  - Institutes of Clinical Medicine, National Yang Ming Chiao Tung University, 
      Hsinchu City 30010, Taiwan.
FAU - Chen, Nai-Ching
AU  - Chen NC
AUID- ORCID: 0000-0003-2684-0377
AD  - Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung 
      University College of Medicine, Kaohsiung 813779, Taiwan.
FAU - Jao, Tzu-Ming
AU  - Jao TM
AUID- ORCID: 0000-0003-2676-292X
AD  - Divisions of Medical Research, Kaohsiung Veterans General Hospital, Kaohsiung 
      813779, Taiwan.
AD  - Institution of Precision Medicine, National Sun Yat-sen University, Kaohsiung 
      813779, Taiwan.
FAU - Chen, Chien-Liang
AU  - Chen CL
AUID- ORCID: 0000-0002-9508-8396
AD  - Institutes of Clinical Medicine, National Yang Ming Chiao Tung University, 
      Hsinchu City 30010, Taiwan.
AD  - Divisions of Medical Research, Kaohsiung Veterans General Hospital, Kaohsiung 
      813779, Taiwan.
AD  - Institution of Precision Medicine, National Sun Yat-sen University, Kaohsiung 
      813779, Taiwan.
AD  - Divisions of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung 813779, 
      Taiwan.
AD  - Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung 
      University, Hsinchu City 30010, Taiwan.
LA  - eng
GR  - KSVGH109-099,107-117/Kaohsiung Veterans General Hospital/
PT  - Journal Article
DEP - 20211113
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 7355X3ROTS (Dextromethorphan)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Dextromethorphan/*pharmacology
MH  - Humans
MH  - Male
MH  - *Muscle, Smooth, Vascular/metabolism/pathology
MH  - *Myocytes, Smooth Muscle/metabolism/pathology
MH  - Oxidative Stress/*drug effects
MH  - Rats
MH  - Rats, Inbred WKY
MH  - *Uremia/drug therapy/metabolism/pathology
MH  - *Vascular Calcification/drug therapy/metabolism/pathology
PMC - PMC8623041
OTO - NOTNLM
OT  - arterial calcification
OT  - dextromethorphan
OT  - smooth muscle cell
COIS- The authors declare no conflict of interest.
EDAT- 2021/11/28 06:00
MHDA- 2021/12/21 06:00
PMCR- 2021/11/13
CRDT- 2021/11/27 01:11
PHST- 2021/07/30 00:00 [received]
PHST- 2021/10/30 00:00 [revised]
PHST- 2021/11/09 00:00 [accepted]
PHST- 2021/11/27 01:11 [entrez]
PHST- 2021/11/28 06:00 [pubmed]
PHST- 2021/12/21 06:00 [medline]
PHST- 2021/11/13 00:00 [pmc-release]
AID - ijms222212277 [pii]
AID - ijms-22-12277 [pii]
AID - 10.3390/ijms222212277 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Nov 13;22(22):12277. doi: 10.3390/ijms222212277.