Environmental Public Health Division, NHEERL, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514.
Toxicol Sci. 2018 May 1;163(1):57-69. doi: 10.1093/toxsci/kfy003.
Fish, olive, and coconut oil dietary supplementation have several cardioprotective benefits, but it is not established if they protect against air pollution-induced adverse effects. We hypothesized that these dietary supplements would attenuate ozone-induced systemic and pulmonary effects. Male Wistar Kyoto rats were fed either a normal diet, or a diet supplemented with fish, olive, or coconut oil for 8 weeks. Animals were then exposed to air or ozone (0.8 ppm), 4 h/day for 2 days. Ozone exposure increased phenylephrine-induced aortic vasocontraction, which was completely abolished in rats fed the fish oil diet. Despite this cardioprotective effect, the fish oil diet increased baseline levels of bronchoalveolar lavage fluid (BALF) markers of lung injury and inflammation. Ozone-induced pulmonary injury/inflammation were comparable in rats on normal, coconut oil, and olive oil diets with altered expression of markers in animals fed the fish oil diet. Fish oil, regardless of exposure, led to enlarged, foamy macrophages in the BALF that coincided with decreased pulmonary mRNA expression of cholesterol transporters, cholesterol receptors, and nuclear receptors. Serum microRNA profile was assessed and demonstrated marked depletion of a variety of microRNAs in animals fed the fish oil diet, several of which were of splenic origin. No ozone-specific changes were noted. Collectively, these data indicate that although fish oil offered vascular protection from ozone exposure, it increased pulmonary injury/inflammation and impaired lipid transport mechanisms resulting in foamy macrophage accumulation, demonstrating the need to be cognizant of potential off-target pulmonary effects that might offset the overall benefit of this vasoprotective supplement.
鱼类、橄榄油和椰子油的饮食补充有多种心脏保护作用,但尚不确定它们是否能预防空气污染引起的不良影响。我们假设这些膳食补充剂可以减轻臭氧引起的全身和肺部效应。雄性 Wistar Kyoto 大鼠喂食正常饮食或补充鱼类、橄榄油或椰子油的饮食 8 周。然后,动物暴露于空气或臭氧(0.8ppm)中,每天 4 小时,共 2 天。臭氧暴露增加了苯肾上腺素诱导的主动脉血管收缩,而喂食鱼油饮食的大鼠则完全消除了这种作用。尽管具有这种心脏保护作用,但鱼油饮食增加了支气管肺泡灌洗液(BALF)中肺损伤和炎症的标志物的基线水平。在正常、椰子油和橄榄油饮食的大鼠中,臭氧诱导的肺损伤/炎症相当,而喂食鱼油饮食的动物的标志物表达发生改变。无论是否暴露于臭氧,鱼油饮食都会导致 BALF 中泡沫状巨噬细胞增大,同时肺内胆固醇转运蛋白、胆固醇受体和核受体的 mRNA 表达减少。评估了血清 microRNA 谱,表明喂食鱼油饮食的动物中存在多种 microRNA 的明显耗竭,其中一些 microRNA 来自脾脏。没有观察到臭氧特异性变化。总的来说,这些数据表明,尽管鱼油提供了对臭氧暴露的血管保护,但它增加了肺部损伤/炎症,并损害了脂质转运机制,导致泡沫状巨噬细胞积聚,这表明需要注意可能抵消这种血管保护补充剂整体益处的潜在非靶向肺部效应。