title: Vitamin C prevents cigarette smoke-induced pulmonary emphysema in mice and provides pulmonary restoration.
abstract: Vitamin C (VC) is a potent antioxidant and is essential for collagen synthesis. We investigated whether VC treatment prevents and cures smoke-induced emphysema in senescence marker protein-30 knockout (SMP30-KO) mice, which cannot synthesize VC. Two smoke-exposure experiments using SMP30-KO mice were conducted. In the first one (a preventive study), 4-month-old mice received minimal VC (0.0375 g/l) [VC(L)] or physiologically sufficient VC (1.5 g/l) [VC(S)] and exposed to cigarette smoke or smoke-free air for 2 months. Pulmonary evaluations followed when the mice were 6 months of age. The second study began after the establishment of smoke-induced emphysema (a treatment study). These mice no longer underwent smoke exposure but received VC(S) or VC(L) treatment for 2 months. Morphometric analysis was performed, and measurements of oxidative stress, collagen synthesis, and vascular endothelial growth factor in the lungs were evaluated. Chronic smoke exposure caused emphysema (29.6% increases of mean linear intercepts [MLI] and 106.5% increases of destructive index compared with the air-only group) in 6-month-old SMP30-KO mice, and this emphysema closely resembled human chronic obstructive pulmonary disease. Smoke-induced emphysema persisted in the VC(L) group after smoking cessation, whereas VC treatment provided pulmonary restoration (18.5% decrease of MLI and 41.3% decrease of destructive index compared with VC(L) group). VC treatment diminished oxidative stress, increased collagen synthesis, and improved vascular endothelial growth factor levels in the lungs. Our results suggest that VC not only prevents smoke-induced emphysema in SMP30-KO mice but also restores emphysematous lungs. Therefore, VC may provide a new therapeutic strategy for treating chronic obstructive pulmonary disease in humans.
authors.affiliation: 1 Division of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Koike
authors.forename: Akihito
authors.initials: A
authors.lastname: Ishigami
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sato
authors.forename: Toyohiro
authors.initials: T
authors.lastname: Hirai
authors.forename: Yiming
authors.initials: Y
authors.lastname: Yuan
authors.forename: Etsuko
authors.initials: E
authors.lastname: Kobayashi
authors.forename: Kazunori
authors.initials: K
authors.lastname: Tobino
authors.forename: Tadashi
authors.initials: T
authors.lastname: Sato
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Sekiya
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yoshinosuke
authors.initials: Y
authors.lastname: Fukuchi
authors.forename: Naoki
authors.initials: N
authors.lastname: Maruyama
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Seyama
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D011656:Pulmonary Emphysema / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D012906:Smoke; D014026:Nicotiana
chemical_list: D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C513324:Rgn protein, mouse; D012906:Smoke; D001205:Ascorbic Acid