Dextromethorphan reduces oxidative stress and inhibits atherosclerosis and neointima formation in mice

Shu Lin Liu, Yi Heng Li, Guey Yueh Shi, Sei Hui Tang, Shinn Jong Jiang, Chia Wei Huang, Ping Yen Liu, Jau Shyong Hong, Hua Lin Wu

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Aims: Macrophage-related oxidative stress plays an important role in the inflammatory process in atherosclerosis. Recently, dextromethorphan (DXM), a common cough-suppressing ingredient with a high safety profile, was found to inhibit the activation of microglia, the resident macrophage in the nervous system. We investigated whether DXM could reduce macrophage production of cytokines and superoxide and the resultant influence on atherosclerosis formation in mice. Methods and results: We used in vitro and in vivo studies to evaluate the DXM inhibitory effect on oxidative stress. Dextromethorphan pretreatment significantly suppressed the production of tumour necrosis factor-α, monocyte chemoattractant protein-1, interleukin-6, interleukin-10, and superoxide in macrophage cell culture after stimulation. Indeed, DXM reduced macrophage nicotinamide adenine dinucleotide phosphate oxidase activity by decreasing membrane translocation of p47phox and p67phox through the inhibition of protein kinase C and extracellular signal-regulated kinase activation. The anti-atherosclerosis effect of DXM was tested using two animal models, apolipoprotein E (apoE)-deficient mice and a mouse carotid ligation model. Dextromethorphan treatment (10-40 mg/kg/day) for 10 weeks in apoE-deficient mice significantly reduced superoxide production in their polymorphonuclear leukocytes and aortas. It significantly decreased the severity of aortic atherosclerosis in the apoE-deficient mice and decreased carotid neointima formation after ligation in C57BL/6 mice. Conclusion: Our data show that DXM, with its novel effect in reducing oxidative stress, significantly reduces atherosclerosis and neointima formation in mice.

Original languageEnglish
Pages (from-to)161-169
Number of pages9
JournalCardiovascular Research
Volume82
Issue number1
DOIs
Publication statusPublished - 2009 Apr 1

Fingerprint

Dextromethorphan
Neointima
Atherosclerosis
Oxidative Stress
Macrophages
Apolipoproteins E
Superoxides
Ligation
Chemokine CCL2
Extracellular Signal-Regulated MAP Kinases
Microglia
NADP
Inbred C57BL Mouse
Cough
Interleukin-10
Protein Kinase C
Nervous System
Aorta
Interleukin-6
Oxidoreductases

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Liu, Shu Lin ; Li, Yi Heng ; Shi, Guey Yueh ; Tang, Sei Hui ; Jiang, Shinn Jong ; Huang, Chia Wei ; Liu, Ping Yen ; Hong, Jau Shyong ; Wu, Hua Lin. / Dextromethorphan reduces oxidative stress and inhibits atherosclerosis and neointima formation in mice. In: Cardiovascular Research. 2009 ; Vol. 82, No. 1. pp. 161-169.
@article{d39ce508eaba4a02be5b8d6b00183d8b,
title = "Dextromethorphan reduces oxidative stress and inhibits atherosclerosis and neointima formation in mice",
abstract = "Aims: Macrophage-related oxidative stress plays an important role in the inflammatory process in atherosclerosis. Recently, dextromethorphan (DXM), a common cough-suppressing ingredient with a high safety profile, was found to inhibit the activation of microglia, the resident macrophage in the nervous system. We investigated whether DXM could reduce macrophage production of cytokines and superoxide and the resultant influence on atherosclerosis formation in mice. Methods and results: We used in vitro and in vivo studies to evaluate the DXM inhibitory effect on oxidative stress. Dextromethorphan pretreatment significantly suppressed the production of tumour necrosis factor-α, monocyte chemoattractant protein-1, interleukin-6, interleukin-10, and superoxide in macrophage cell culture after stimulation. Indeed, DXM reduced macrophage nicotinamide adenine dinucleotide phosphate oxidase activity by decreasing membrane translocation of p47phox and p67phox through the inhibition of protein kinase C and extracellular signal-regulated kinase activation. The anti-atherosclerosis effect of DXM was tested using two animal models, apolipoprotein E (apoE)-deficient mice and a mouse carotid ligation model. Dextromethorphan treatment (10-40 mg/kg/day) for 10 weeks in apoE-deficient mice significantly reduced superoxide production in their polymorphonuclear leukocytes and aortas. It significantly decreased the severity of aortic atherosclerosis in the apoE-deficient mice and decreased carotid neointima formation after ligation in C57BL/6 mice. Conclusion: Our data show that DXM, with its novel effect in reducing oxidative stress, significantly reduces atherosclerosis and neointima formation in mice.",
author = "Liu, {Shu Lin} and Li, {Yi Heng} and Shi, {Guey Yueh} and Tang, {Sei Hui} and Jiang, {Shinn Jong} and Huang, {Chia Wei} and Liu, {Ping Yen} and Hong, {Jau Shyong} and Wu, {Hua Lin}",
year = "2009",
month = "4",
day = "1",
doi = "10.1093/cvr/cvp043",
language = "English",
volume = "82",
pages = "161--169",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "1",

}

Dextromethorphan reduces oxidative stress and inhibits atherosclerosis and neointima formation in mice. / Liu, Shu Lin; Li, Yi Heng; Shi, Guey Yueh; Tang, Sei Hui; Jiang, Shinn Jong; Huang, Chia Wei; Liu, Ping Yen; Hong, Jau Shyong; Wu, Hua Lin.

In: Cardiovascular Research, Vol. 82, No. 1, 01.04.2009, p. 161-169.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Dextromethorphan reduces oxidative stress and inhibits atherosclerosis and neointima formation in mice

AU - Liu, Shu Lin

AU - Li, Yi Heng

AU - Shi, Guey Yueh

AU - Tang, Sei Hui

AU - Jiang, Shinn Jong

AU - Huang, Chia Wei

AU - Liu, Ping Yen

AU - Hong, Jau Shyong

AU - Wu, Hua Lin

PY - 2009/4/1

Y1 - 2009/4/1

N2 - Aims: Macrophage-related oxidative stress plays an important role in the inflammatory process in atherosclerosis. Recently, dextromethorphan (DXM), a common cough-suppressing ingredient with a high safety profile, was found to inhibit the activation of microglia, the resident macrophage in the nervous system. We investigated whether DXM could reduce macrophage production of cytokines and superoxide and the resultant influence on atherosclerosis formation in mice. Methods and results: We used in vitro and in vivo studies to evaluate the DXM inhibitory effect on oxidative stress. Dextromethorphan pretreatment significantly suppressed the production of tumour necrosis factor-α, monocyte chemoattractant protein-1, interleukin-6, interleukin-10, and superoxide in macrophage cell culture after stimulation. Indeed, DXM reduced macrophage nicotinamide adenine dinucleotide phosphate oxidase activity by decreasing membrane translocation of p47phox and p67phox through the inhibition of protein kinase C and extracellular signal-regulated kinase activation. The anti-atherosclerosis effect of DXM was tested using two animal models, apolipoprotein E (apoE)-deficient mice and a mouse carotid ligation model. Dextromethorphan treatment (10-40 mg/kg/day) for 10 weeks in apoE-deficient mice significantly reduced superoxide production in their polymorphonuclear leukocytes and aortas. It significantly decreased the severity of aortic atherosclerosis in the apoE-deficient mice and decreased carotid neointima formation after ligation in C57BL/6 mice. Conclusion: Our data show that DXM, with its novel effect in reducing oxidative stress, significantly reduces atherosclerosis and neointima formation in mice.

AB - Aims: Macrophage-related oxidative stress plays an important role in the inflammatory process in atherosclerosis. Recently, dextromethorphan (DXM), a common cough-suppressing ingredient with a high safety profile, was found to inhibit the activation of microglia, the resident macrophage in the nervous system. We investigated whether DXM could reduce macrophage production of cytokines and superoxide and the resultant influence on atherosclerosis formation in mice. Methods and results: We used in vitro and in vivo studies to evaluate the DXM inhibitory effect on oxidative stress. Dextromethorphan pretreatment significantly suppressed the production of tumour necrosis factor-α, monocyte chemoattractant protein-1, interleukin-6, interleukin-10, and superoxide in macrophage cell culture after stimulation. Indeed, DXM reduced macrophage nicotinamide adenine dinucleotide phosphate oxidase activity by decreasing membrane translocation of p47phox and p67phox through the inhibition of protein kinase C and extracellular signal-regulated kinase activation. The anti-atherosclerosis effect of DXM was tested using two animal models, apolipoprotein E (apoE)-deficient mice and a mouse carotid ligation model. Dextromethorphan treatment (10-40 mg/kg/day) for 10 weeks in apoE-deficient mice significantly reduced superoxide production in their polymorphonuclear leukocytes and aortas. It significantly decreased the severity of aortic atherosclerosis in the apoE-deficient mice and decreased carotid neointima formation after ligation in C57BL/6 mice. Conclusion: Our data show that DXM, with its novel effect in reducing oxidative stress, significantly reduces atherosclerosis and neointima formation in mice.

UR - http://www.scopus.com/inward/record.url?scp=62349119913&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=62349119913&partnerID=8YFLogxK

U2 - 10.1093/cvr/cvp043

DO - 10.1093/cvr/cvp043

M3 - Article

C2 - 19189960

AN - SCOPUS:62349119913

VL - 82

SP - 161

EP - 169

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 1

ER -