title: Neutrophil superoxide-anion generating capacity in chronic smoking: effect of long-term alpha-tocopherol therapy.
abstract: We investigated whether long-term alpha-tocopherol therapy in chronic smoking affects superoxide generating capacity of neutrophils ex vivo. To this purpose, we randomly assigned 128 male chronic smokers (37 +/- 21 pack years of smoking) to treatment with placebo (n = 64) or alpha-tocopherol (400 IU dL-a-tocopherol daily, n = 64). After two years of therapy, we measured phorbol 12-myristate 13-acetate-induced superoxide production of isolated neutrophils and of diluted whole blood by monitoring reduction of ferricytochrome c and luminol-enhanced peroxidase-catalyzed chemiluminescence. Plasma lipids and lipoproteins were not different between the two treatment groups. As expected, concentrations of alpha-tocopherol in plasma and in low-density lipoproteins were markedly elevated in the supplemented group compared to the placebo group (+ 120%, P < 0.0001 and + 83%, P < 0.0001, respectively). Consequently, resistance to in vitro oxidation of low-density lipoproteins (reflected by lag time of conjugated diene formation) was higher in the supplemented group than in the placebo group (+ 22%, P < 0.0001). Superoxide generating capacity of neutrophils and superoxide production in diluted whole blood did not differ between alpha-tocopherol and placebo group. It is concluded that in chronic smoking long-term supranormal alpha-tocopherol intake does not reduce neutrophil superoxide-anion generating capacity, despite large increases in the concentrations of alpha-tocopherol in plasma and in low-density lipoproteins.
authors.affiliation: Department of Medicine, Division of General Internal Medicine, University Medical Center Nijmegen. B.vanTits@AIG.umcn.nl
authors.forename: Lambertus J H
authors.initials: LJ
authors.lastname: van Tits
authors.forename: Frouwkje
authors.initials: F
authors.lastname: de Waart
authors.forename: Heidi L M
authors.initials: HL
authors.lastname: Hak-Lemmers
authors.forename: Jacqueline
authors.initials: J
authors.lastname: de Graaf
authors.forename: Pierre N M
authors.initials: PN
authors.lastname: Demacker
authors.forename: Anton F H
authors.initials: AF
authors.lastname: Stalenhoef
mesh_terms: D000368:Aged; D002784:Cholesterol / Q000097:blood; D004311:Double-Blind Method; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects* / Q000097:blood / Q000378:metabolism*; D013481:Superoxides / Q000097:blood / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D024502:alpha-Tocopherol / Q000097:blood / Q000627:therapeutic use*
chemical_list: D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; D013481:Superoxides; D002784:Cholesterol; D024502:alpha-Tocopherol; D013755:Tetradecanoylphorbol Acetate