title: β-Cryptoxanthin supplementation prevents cigarette smoke-induced lung inflammation, oxidative damage, and squamous metaplasia in ferrets.
abstract: In epidemiologic studies, high intake of β-cryptoxanthin has been associated with a decreased risk of lung cancer, particularly among current smokers. However, data are not available from well-controlled animal studies to examine the effects of β-cryptoxanthin on cigarette smoke-induced lung lesions, and the biological mechanisms by which β-cryptoxanthin might affect lung carcinogenesis. We evaluated the effects of β-cryptoxanthin supplementation on cigarette smoke-induced squamous metaplasia, inflammation, and changes in protein levels of proinflammatory cytokine [tumor necrosis factor alpha (TNFα)] and transcription factors [nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1)], as well as on smoke-induced oxidative DNA damage [8-hydroxy-2'-deoxyguanosine (8-OHdG)] in the lung tissue of ferrets. Thirty-six male ferrets were assigned to cigarette smoke exposure or no exposure and to low-dose, or high-dose β-cryptoxanthin, or no dose (2 × 3 factorial design) for 3 months. β-Cryptoxanthin supplementation dose-dependently increased plasma and lung β-cryptoxanthin levels in ferrets, whereas cigarette smoke exposure lowered plasma and lung β-cryptoxanthin levels. β-Cryptoxanthin at both doses significantly decreased smoke-induced lung squamous metaplasia and inflammation. β-Cryptoxanthin also substantially reduced smoke-elevated TNFα levels in alveolar, bronchial, bronchiolar, and bronchial serous/mucous gland epithelial cells and in lung macrophages. Moreover, β-cryptoxanthin decreased smoke-induced activation of NF-κB, expression of AP-1 and levels of 8-OHdG. The beneficial effects of β-cryptoxanthin were stronger for high-dose β-cryptoxanthin than for low-dose β-cryptoxanthin. Data from this study indicate that β-cryptoxanthin provides a beneficial effect against cigarette smoke-induced inflammation, oxidative DNA damage and squamous metaplasia in the lungs.
authors.affiliation: Nutrition and Cancer Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA. chun.liu@tufts.edu
authors.forename: Chun
authors.initials: C
authors.lastname: Liu
authors.forename: Roderick T
authors.initials: RT
authors.lastname: Bronson
authors.forename: Robert M
authors.initials: RM
authors.lastname: Russell
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Wang
mesh_terms: D000818:Animals; D065366:Cryptoxanthins; D016207:Cytokines / Q000378:metabolism; D004249:DNA Damage; D019587:Dietary Supplements; D005289:Ferrets; D005819:Genetic Markers; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000517:prevention & control*; D008168:Lung / Q000473:pathology*; D008297:Male; D008679:Metaplasia / Q000517:prevention & control*; D018384:Oxidative Stress; D012907:Smoking; D014026:Nicotiana / Q000009:adverse effects*; D024341:Xanthophylls / Q000494:pharmacology*
chemical_list: D065366:Cryptoxanthins; D016207:Cytokines; D005819:Genetic Markers; D024341:Xanthophylls