Nicholas School of the Environment, Duke University, Durham, NC, USA; Duke Global Health Institute, Duke University, Durham, NC, USA.
Department of Civil and Environmental Engineering, Duke University, Durham, NC, USA.
Sci Total Environ. 2021 Jun 15;773:145709. doi: 10.1016/j.scitotenv.2021.145709. Epub 2021 Feb 6.
Heightening oxidative stress and inflammation is an important pathophysiological mechanism underlying air pollution health effects in people with asthma. Melatonin can suppress oxidative stress and inflammation in pulmonary and circulatory systems. However, the role of melatonin in the oxidative stress and physiological responses to air pollution exposure has not been examined in children with asthma.
In this panel study of 43 asthmatic children (5-13 years old), each child had 4 clinic visits with a 2-week interval between two consecutive visits. At each visit, urine samples were collected and subsequently analyzed for 6-sulfatoxymelatonin (aMT6s) as a surrogate of circulating melatonin and for malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) as two biomarkers of systemic oxidative stress. At each clinic visit, children were measured for pulmonary function and fractional exhaled nitric oxide (FeNO, a marker of pulmonary inflammation). None of the children reported to have taking melatonin supplementation. Concentrations of indoor and ambient PM and ozone (O) were combined with individual time-activity data to calculate personal air pollutant exposures.
We found that interquartile range increases in urinary MDA and 8-OHdG concentrations were associated with significantly increased urinary aMT6s concentrations by 73.4% (95% CI: 52.6% to 97.0%) and 41.7% (22.8% to 63.4%), respectively. Increases in daily personal exposure to O and to PM were each associated with increased urinary aMT6s concentrations. Increasing urinary aMT6s concentrations were associated with decreased FeNO and resonant frequency, indicating improved airway inflammation and lung elasticity, respectively.
The results suggest that systemic oxidative stress heightened by air pollution exposure may stimulate melatonin excretion as a defense mechanism to alleviate the adverse effects.
在哮喘患者中，增强氧化应激和炎症是空气污染对健康影响的一个重要病理生理学机制。褪黑素可以抑制肺和循环系统中的氧化应激和炎症。然而，褪黑素在哮喘儿童对空气污染暴露的氧化应激和生理反应中的作用尚未得到研究。
在这项对 43 名哮喘儿童（5-13 岁）的面板研究中，每个孩子在两次连续就诊之间有 4 次就诊，每次就诊时采集尿样，随后分析 6-硫酸褪黑素（aMT6s）作为循环褪黑素的替代物，以及丙二醛（MDA）和 8-羟基-2'-脱氧鸟苷（8-OHdG）作为两种全身氧化应激生物标志物。在每次就诊时，儿童还进行肺功能和呼出气一氧化氮分数（FeNO，肺部炎症的标志物）测量。没有儿童报告服用褪黑素补充剂。将室内和环境 PM 和臭氧（O）浓度与个体时间活动数据相结合，计算个人空气污染物暴露量。
我们发现，尿 MDA 和 8-OHdG 浓度的四分位间距增加与尿 aMT6s 浓度分别显著增加 73.4%（95%CI：52.6%至 97.0%）和 41.7%（22.8%至 63.4%）有关。每日个人接触 O 和 PM 的增加均与尿 aMT6s 浓度增加有关。尿 aMT6s 浓度的增加与 FeNO 和共振频率降低有关，分别表明气道炎症减轻和肺弹性增加。
结果表明，空气污染暴露引起的全身氧化应激增加可能会刺激褪黑素排泄作为一种防御机制，以减轻不良影响。
