Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666 Al Ain, UAE.
Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666 Al Ain, UAE.
Nutrients. 2018 Feb 26;10(3):263. doi: 10.3390/nu10030263.
Numerous studies have shown that acute particulate air pollution exposure is linked with pulmonary adverse effects, including alterations of pulmonary function, inflammation, and oxidative stress. Nootkatone, a constituent of grapefruit, has antioxidant and anti-inflammatory effects. However, the effect of nootkatone on lung toxicity has not been reported so far. In this study we evaluated the possible protective effects of nootkatone on diesel exhaust particles (DEP)-induced lung toxicity, and the possible mechanisms underlying these effects. Mice were intratracheally (i.t.) instilled with either DEP (30 µg/mouse) or saline (control). Nootkatone was given to mice by gavage, 1 h before i.t. instillation, with either DEP or saline. Twenty-four hours following DEP exposure, several physiological and biochemical endpoints were assessed. Nootkatone pretreatment significantly prevented the DEP-induced increase in airway resistance in vivo, decreased neutrophil infiltration in bronchoalveolar lavage fluid, and abated macrophage and neutrophil infiltration in the lung interstitium, assessed by histolopathology. Moreover, DEP caused a significant increase in lung concentrations of 8-isoprostane and tumor necrosis factor α, and decreased the reduced glutathione concentration and total nitric oxide activity. These actions were all significantly alleviated by nootkatone pretreatment. Similarly, nootkatone prevented DEP-induced DNA damage and prevented the proteolytic cleavage of caspase-3. Moreover, nootkatone inhibited nuclear factor-kappaB (NF-κB) induced by DEP. We conclude that nootkatone prevented the DEP-induced increase in airway resistance, lung inflammation, oxidative stress, and the subsequent DNA damage and apoptosis through a mechanism involving inhibition of NF-κB activation. Nootkatone could possibly be considered a beneficial protective agent against air pollution-induced respiratory adverse effects.
大量研究表明，急性颗粒物空气污染暴露与肺部不良效应有关，包括肺功能改变、炎症和氧化应激。诺卡酮是葡萄柚的一种成分，具有抗氧化和抗炎作用。然而，迄今为止，尚未有关于诺卡酮对肺毒性影响的报道。在这项研究中，我们评估了诺卡酮对柴油机排气颗粒物（DEP）诱导的肺毒性的可能保护作用，以及这些作用的可能机制。通过气管内（i.t.）滴注，将小鼠分别用 DEP（30 µg/只）或生理盐水（对照）处理。诺卡酮通过灌胃给药，在 i.t.滴注前 1 小时给予小鼠，同时给予 DEP 或生理盐水。在 DEP 暴露 24 小时后，评估了几个生理和生化终点。诺卡酮预处理显著防止了 DEP 诱导的体内气道阻力增加，减少了支气管肺泡灌洗液中的中性粒细胞浸润，并减轻了组织病理学评估的肺间质中巨噬细胞和中性粒细胞浸润。此外，DEP 导致肺组织中 8-异前列腺素和肿瘤坏死因子 α 的浓度显著增加，而还原型谷胱甘肽浓度和总一氧化氮活性降低。这些作用均通过诺卡酮预处理得到显著缓解。同样，诺卡酮防止了 DEP 诱导的 DNA 损伤，并防止了 caspase-3 的蛋白水解切割。此外，诺卡酮抑制了 DEP 诱导的核因子-κB（NF-κB）的激活。我们得出结论，诺卡酮通过抑制 NF-κB 的激活，防止了 DEP 诱导的气道阻力增加、肺部炎症、氧化应激以及随后的 DNA 损伤和细胞凋亡。诺卡酮可能被认为是一种有益的保护剂，可预防空气污染引起的呼吸道不良效应。
