Oxidants in the gas phase of cigarette smoke pass through the lung alveolar wall and raise systemic oxidative stress.
Cigarette smoking-induced oxidative stress plays a key role in the pathogenesis of atherosclerosis in smokers. Aqueous cigarette smoke extract (CSE) contains stable oxidants, peroxynitrite-like reactants, which have the ability to oxidize and nitrate low-density lipoprotein (LDL). We examined whether oxidants in CSE can penetrate into the blood through the lung alveolar wall and cause oxidative vascular injury. The oxidants in CSE and sodium peroxynitrite could easily pass through the reconstituted basement membrane. When CSE or sodium peroxynitrite solution was infused into the alveolar air space of an isolated rat lung mounted in tyrosine solution, CSE gradually increased the 3-nitrotyrosine levels in the external tyrosine solution while sodium peroxynitrite caused a rapid increase. CSE did not activate the rat alveolar macrophages. When rats were acutely exposed to the gas phase of cigarette smoke from which tar and nicotine had been removed, both serum levels of 3-nitrotyrosine and 8-hydroxy-2'-deoxyguanine, oxidative stress markers, rapidly increased. Our results demonstrate that relatively stable oxidants in CSE can pass through the pulmonary alveolar wall into the blood and induce systemic oxidative stress, which most likely facilitates oxidative modification of LDL and endothelial dysfunction, explaining early key events in the development of atherosclerosis.
Yamaguchi
Yu
Y
Department of Pharmacology, School of Pharmaceutical Sciences, Mukogawa Women's University, Kyuban-cho, Nishinomiya, Japan. yusan@mukogawa-u.ac.jp
Nasu
Fumiko
F
Harada
Atsuko
A
Kunitomo
Masaru
M
D000818:Animals; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D007700:Kinetics; D008297:Male; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012906:Smoke; D012907:Smoking / Q000009:adverse effects*; D013047:Specific Pathogen-Free Organisms; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood
D016877:Oxidants; D012906:Smoke; C002744:3-nitrotyrosine; D014443:Tyrosine; D003849:Deoxyguanosine