β-Cryptoxanthin Supplementation Prevents Cigarette Smoke-Induced Lung Inflammation, Oxidative Damage, and Squamous Metaplasia in Ferrets

In epidemiologic studies, high intake of beta-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 beta-cryptoxanthin on cigarette smoke-induced lung lesions, and the biological mechanisms by which beta-cryptoxanthin might affect lung carcinogenesis. We evaluated the effects of beta-cryptoxanthin supplementation on cigarette smoke-induced squamous metaplasia, inflammation, and changes in protein levels of proinflammatory cytokine [tumor necrosis factor alpha (TNF alpha)] and transcription factors [nuclear factor kappa B (NF-kappa B) 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 beta-cryptoxanthin, or no dose (2 x 3 factorial design) for 3 months. beta-Cryptoxanthin supplementation dose-dependently increased plasma and lung beta-cryptoxanthin levels in ferrets, whereas cigarette smoke exposure lowered plasma and lung beta-cryptoxanthin levels. beta-Cryptoxanthin at both doses significantly decreased smoke-induced lung squamous metaplasia and inflammation. beta-Cryptoxanthin also substantially reduced smoke-elevated TNF alpha levels in alveolar, bronchial, bronchiolar, and bronchial serous/mucous gland epithelial cells and in lung macrophages. Moreover, beta-cryptoxanthin decreased smoke-induced activation of NF-kappa B, expression of AP-1 and levels of 8-OHdG. The beneficial effects of beta-cryptoxanthin were stronger for high-dose beta-cryptoxanthin than for low-dose beta-cryptoxanthin. Data from this study indicate that beta-cryptoxanthin provides a beneficial effect against cigarette smoke-induced inflammation, oxidative DNA damage and squamous metaplasia in the lungs. Cancer Prev Res; 4(8); 1255-66. (C) 2011 AACR.