Treatment with dextromethorphan improves endothelial function, inflammation and oxidative stress in male heavy smokers.

Abstract

Dextromethorphan (DM) is reported to reduce the inflammation-mediated degeneration of dopaminergic neurons. The goal of this study was to test if DM can improve the endothelial dysfunction and inflammatory markers in heavy smokers. Forty habitual smoking healthy male volunteers (mean age, 31.5 +/- 1.4 years) were randomly given either DM (120 mg day(-1)) or a placebo for 6 months. We determined endothelial function using the brachial artery diameter changes in flow-mediated dilatation (FMD) and measured their inflammatory and oxidative markers. A sex-and-age matched non-smoking group (n = 20) was compared as normal parameters. Habitual smokers showed impaired baseline endothelial function in FMD (smoking vs. non-smoking: 6.3 +/- 1.8 vs. 10.2 +/- 2.3% respectively, P < 0.01). Without change in smoking behavior, lipid and metabolic parameters, a significant increase in FMD was found in the DM-treated group (32%), accompanied by a decrease in high-sensitivity C-reactive protein (hs-CRP), phospholipase A(2), matrix metalloproteinase-3, interleukin 6 (IL-6) and tumor necrosis factor-alpha receptor II (TNF-alpha RII) (all P < 0.05), but unchanged in von Willebrand factor (VWF)and plasminogen activator inhibitor-1 (PAI-1). An increase in plasma glutathione peroxidase and a decrease in spot urinary excretion of 8-epi-prostaglandin F(2a) were found in DM-treated smokers. Our study suggests that a 6-month treatment with DM can improve endothelial function and attenuate vascular oxidative stress and inflammation markers in habitual smokers.