Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore; Immunology Program, Life Science Institute, National University of Singapore, Singapore.
Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore; Singapore-MIT Alliance for Research and Technology (SMART), National University of Singapore, Singapore.
Free Radic Biol Med. 2017 Sep;110:332-344. doi: 10.1016/j.freeradbiomed.2017.06.023. Epub 2017 Jul 3.
Inflammation and oxidative stress contribute to emphysema in COPD. Although corticosteroids are the standard of care for COPD, they do not reduce oxidative stress, and a subset of patients is steroid-resistant. Vitamin E isoform γ-tocotrienol possesses both anti-inflammatory and anti-oxidative properties that may protect against emphysema. We aimed to establish the therapeutic potential of γ-tocotrienol in cigarette smoke-induced COPD models in comparison with prednisolone. BALB/c mice were exposed to cigarette smoke for 2 weeks or 2 months. γ-Tocotrienol and prednisolone were given orally. Bronchoalveolar lavage (BAL) fluid and lung tissues were assessed for inflammation, oxidative damage, and regulation of transcription factor activities. Emphysema and lung function were also evaluated. γ-Tocotrienol dose-dependently reduced cigarette smoke-induced BAL fluid neutrophil counts and levels of cytokines, chemokines and oxidative damage biomarkers, and pulmonary pro-inflammatory and pro-oxidant gene expression, but restored lung endogenous antioxidant activities. γ-Tocotrienol acted by inhibiting nuclear translocation of STAT3 and NF-κB, and up-regulating Nrf2 activation in the lungs. In mice exposed to 2-month cigarette smoke, γ-tocotrienol ameliorated bronchial epithelium thickening and destruction of alveolar sacs in lungs, and improved lung functions. In comparison with prednisolone, γ-tocotrienol demonstrated better anti-oxidative efficacy, and protection against emphysema and lung function in COPD. We revealed for the first time the anti-inflammatory and antioxidant efficacies of γ-tocotrienol in cigarette smoke-induced COPD models. In addition, γ-tocotrienol was able to attenuate emphysematous lesions and improve lung function in COPD. γ-Tocotrienol may have therapeutic potential for the treatment of COPD.
炎症和氧化应激导致 COPD 发生肺气肿。虽然皮质类固醇是 COPD 的标准治疗方法，但它们不能降低氧化应激，并且一部分患者对皮质类固醇耐药。维生素 E 异构体 γ-生育三烯酚具有抗炎和抗氧化特性，可能有助于预防肺气肿。我们旨在比较 γ-生育三烯酚与泼尼松龙在香烟烟雾诱导的 COPD 模型中的治疗潜力。BALB/c 小鼠暴露于香烟烟雾 2 周或 2 个月。γ-生育三烯酚和泼尼松龙口服给予。评估支气管肺泡灌洗液 (BAL) 和肺组织的炎症、氧化损伤和转录因子活性调节。还评估了肺气肿和肺功能。γ-生育三烯酚呈剂量依赖性降低香烟烟雾诱导的 BAL 液中性粒细胞计数和细胞因子、趋化因子和氧化损伤生物标志物水平，以及肺内促炎和促氧化剂基因表达，但恢复了肺内源性抗氧化活性。γ-生育三烯酚通过抑制 STAT3 和 NF-κB 的核易位，并上调肺中的 Nrf2 激活来发挥作用。在暴露于 2 个月香烟烟雾的小鼠中，γ-生育三烯酚改善了支气管上皮细胞增厚和肺泡囊破坏，并改善了肺功能。与泼尼松龙相比，γ-生育三烯酚显示出更好的抗氧化功效，并能预防 COPD 中的肺气肿和肺功能下降。我们首次揭示了 γ-生育三烯酚在香烟烟雾诱导的 COPD 模型中的抗炎和抗氧化功效。此外，γ-生育三烯酚能够减轻肺气肿病变并改善 COPD 中的肺功能。γ-生育三烯酚可能具有治疗 COPD 的潜力。
