Role of endogenous melatonin in pathophysiologic and oxidative stress responses to personal air pollutant exposures in asthmatic children

Linchen He; Christina Norris; Xiaoxing Cui; Zhen Li; Karoline K Barkjohn; Yanbo Teng; Lin Fang; Lili Lin; Qian Wang; Xiaojian Zhou; Jianguo Hong; Feng Li; Yinping Zhang; James J Schauer; Marilyn Black; Michael H Bergin; Junfeng Jim Zhang

doi:10.1016/j.scitotenv.2021.145709

Role of endogenous melatonin in pathophysiologic and oxidative stress responses to personal air pollutant exposures in asthmatic children

Sci Total Environ. 2021 Jun 15:773:145709. doi: 10.1016/j.scitotenv.2021.145709. Epub 2021 Feb 6.

Authors

Linchen He¹, Christina Norris², Xiaoxing Cui³, Zhen Li⁴, Karoline K Barkjohn², Yanbo Teng⁵, Lin Fang⁶, Lili Lin⁴, Qian Wang⁴, Xiaojian Zhou⁴, Jianguo Hong⁴, Feng Li⁷, Yinping Zhang⁶, James J Schauer⁸, Marilyn Black⁹, Michael H Bergin², Junfeng Jim Zhang¹⁰

Affiliations

¹ Nicholas School of the Environment, Duke University, Durham, NC, USA; Duke Global Health Institute, Duke University, Durham, NC, USA.
² Department of Civil and Environmental Engineering, Duke University, Durham, NC, USA.
³ Nicholas School of the Environment, Duke University, Durham, NC, USA.
⁴ Department of Pediatrics, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
⁵ Duke Kunshan University, Kunshan, Jiangsu Province, China.
⁶ Department of Building Science, Tsinghua University, Beijing, China; Beijing Key Laboratory of Indoor Air Quality Evaluation and Control, Beijing, China.
⁷ Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
⁸ Department of Civil and Environmental Engineering, College of Engineering, University of Wisconsin-Madison, Madison, WI, USA.
⁹ Underwriters Laboratories, Inc., Marietta, GA, USA.
¹⁰ Nicholas School of the Environment, Duke University, Durham, NC, USA; Duke Global Health Institute, Duke University, Durham, NC, USA; Duke Kunshan University, Kunshan, Jiangsu Province, China. Electronic address: junfeng.zhang@duke.edu.

PMID: 33940766
DOI: 10.1016/j.scitotenv.2021.145709

Abstract

Background: 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.

Methods: 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_2.5 and ozone (O₃) were combined with individual time-activity data to calculate personal air pollutant exposures.

Results: 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 O₃ and to PM_2.5 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.

Conclusion: 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.

Keywords: Air pollution; Airway mechanics; Lung function; Melatonin; Oxidative stress; Pulmonary physiology.

MeSH terms

Adolescent
Air Pollutants* / adverse effects
Air Pollutants* / analysis
Asthma*
Child
Child, Preschool
Humans
Melatonin*
Oxidative Stress
Particulate Matter / adverse effects
Particulate Matter / analysis

Substances

Air Pollutants
Particulate Matter
Melatonin