Greater gamma-tocopherol status during acute smoking abstinence with nicotine replacement therapy improved vascular endothelial function by decreasing 8-iso-15(S)-prostaglandin F-2 alpha

摘要

Nicotine replacement therapy (NRT) improves the long-term success rate of smoking cessation, but induces oxidative stress and inflammatory responses that may delay the restoration of vascular endothelial function (VEF). No studies have examined co-therapy of NRT-assisted smoking abstinence with gamma-tocopherol (gamma-T), a vitamin E form with antioxidant and anti-inflammatory activities, on improvements in VEF. In a randomized, double-blind, placebo-controlled study, healthy smokers (25 +/- 1 y old; mean +/- SEM) received NRT and abstained from smoking for 24 h with placebo (n = 12) or oral administration of gamma-T-rich mixture of tocopherols (gamma-TmT; n = 11) that provided 500mg gamma-T. Brachial artery flow-mediated dilation (FMD), and biomarkers of nitric oxide metabolism, antioxidant status, inflammation, and lipid peroxidation [8-iso-prostaglandin F-2 alpha stereoisomers (8-iso-15(R)-PGF(2 alpha) and 8-iso-15(S)-PGF(2 alpha))] were measured prior to and after 24 h of smoking abstinence. Smoking abstinence with NRT regardless of gamma-TmT similarly decreased urinary naphthol (P<0.05) without affecting plasma cotinine. gamma-TmT increased plasma gamma-T by 4-times and the urinary metabolite of gamma-T, gamma-carboxyethyl-chromanol, by three times. Smoking abstinence with gamma-TmT, but not smoking abstinence alone, increased FMD without affecting plasma nitrateitrite or the ratio of asymmetric dimethylarginine/arginine. Urinary 8-iso-15(S)-PGF(2 alpha) decreased only in those receiving gamma-TmT and was inversely correlated to FMD (R = -0.43, P<0.05). Circulating markers of inflammation were unaffected by smoking abstinence or gamma-TmT. Short-term NRT-assisted smoking abstinence with gamma-TmT, but not NRT-assisted smoking abstinence alone, improved VEF by decreasing 8-iso-15(S)-PGF(2 alpha), a vasoconstrictor that was otherwise unaffected by NRT-assisted smoking abstinence.