β-Cryptoxanthin supplementation prevents cigarette smoke-induced lung inflammation, oxidative damage, and squamous metaplasia in ferrets.
β-Cryptoxanthin supplementation prevents cigarette smoke-induced lung inflammation, oxidative damage, and squamous metaplasia in ferrets.
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DOI：
10.1158/1940-6207.capr-10-0384
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发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Wang XD
中科院分区：
文献类型：
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作者：
Liu C;Bronson RT;Russell RM;Wang XD
在流行病学研究中，大量摄入β-隐黄质与肺癌风险降低有关，特别是在当前吸烟者中。然而，并没有来自对照良好的动物研究的数据来检验β-隐黄质对香烟引起的肺部病变的影响，以及β-隐黄质可能影响肺癌发生的生物学机制。我们评估了补充β-隐黄质对烟熏诱导的雪貂肺组织鳞状皮化生、炎症、促炎细胞因子[肿瘤坏死因子α (TNFα)]和转录因子[核因子κB （NF-κB）和激活蛋白-1 (AP-1)]蛋白水平的影响，以及对烟熏诱导的DNA氧化损伤[8-羟基-2 ' -脱氧鸟苷（8-OHdG）]的影响。36只雄性雪貂被分配到香烟烟雾暴露组或不暴露组，以及低剂量、高剂量或无剂量组（2 × 3因子设计），为期3个月。β-隐黄质增加雪貂血浆和肺中β-隐黄质水平，而香烟烟雾暴露降低血浆和肺中β-隐黄质水平。两种剂量的β-隐黄素均可显著降低烟雾引起的肺鳞状皮化生和炎症。β-隐黄质还能显著降低烟雾引起的肺泡、支气管、细支气管和支气管浆液/黏液腺上皮细胞和肺巨噬细胞中TNFα水平升高。此外，β-隐黄质降低了烟雾诱导的NF-κB活化、AP-1表达和8-OHdG水平。高剂量β-隐黄质的有益作用强于低剂量β-隐黄质。这项研究的数据表明，β-隐黄质对香烟引起的炎症、氧化性DNA损伤和肺部鳞状皮化生有有益的作用。
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 pro-inflammatory 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.