Increased serum iron may contribute to enhanced oxidation of low-density lipoprotein in smokers in part through changes in lipoxygenase and catalase.
BACKGROUND
Increased oxidative stress is considered to be causative for cardiovascular disease (CVD) in smokers, but its mechanisms are still unclear. We compared oxidative stress markers between male smokers and male nonsmokers.


METHODS
Twenty-three healthy men (11 nonsmokers and 12 smokers) were enrolled, and blood samples after 12 h of fasting were collected to assess plasma lipids and oxidative stress markers. The effects of iron loading on 12-lipoxygenase (12-LO) expression and activity in human umbilical vein endothelial cells (HUVECs) were tested in vitro to investigate the relevance of iron to oxidation potential in vivo.


RESULTS
Higher levels of plasma-oxidized low-density lipoprotein (LDL) and lipid peroxide (LPO), and higher oxidizability of LDL were observed in smokers than in nonsmokers. Higher levels of serum iron and lower levels of plasma vitamin E were observed in smokers than in nonsmokers. Stepwise multiple regression analysis showed that serum iron was an independent determinant for both plasma-oxidized LDL and lag time of LDL oxidation. Iron loading enhanced 12-LO expression threefold and its activity 1.5-fold. Moreover, iron loading decreased catalase expression by 50% and significantly reduced its activity by 75%.


CONCLUSIONS
Enhanced oxidative stress in smokers may be due to increased iron levels. Iron-induced modulation of expression and activity of 12-LO and catalase may be relevant to increased iron-related oxidative stress as observed in smokers.
Yoshida
Hiroshi
H
Department of General Medicine, Jikei University School of Medicine, Chiba, Japan. hyoshida@jikei.ac.jp
Sasaki
Kayoko
K
Hirowatari
Yuji
Y
Kurosawa
Hideo
H
Sato
Noriko
N
Furutani
Nobuyuki
N
Tada
Norio
N
D000328:Adult; D015992:Body Mass Index; D002374:Catalase / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007501:Iron / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D008084:Lipoxygenase / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D012907:Smoking / Q000097:blood*
D008077:Lipoproteins, LDL; D006861:Hydrogen Peroxide; D007501:Iron; D002374:Catalase; D005979:Glutathione Peroxidase; D008084:Lipoxygenase