The Effects of Melatonin on the Relationship between Air Pollution Levels and Biomarkers of Oxidative Stress and Platelet Activation in Healthy Young Adults

Abstract

Urinary free malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) as biomarkers of oxidative stress as well as soluble P-selectin as a biomarker of platelet activation have been associated with air pollution exposure. However, the results have not been consistent across studies. We hypothesize that this inconsistency might be due to modification of circulating melatonin, a free radical scavenger and a key factor in the DNA damage repair system, on MDA and 8-OHdG responses to reactive oxygen species induced by air pollution exposure. Melatonin also regulates PPARγ/FUNDC1/ mitophagy pathways, hence affecting P-selectin level. We conducted a longitudinal study involving 70 healthy young adults living on a hospital campus in Shanghai. Indoor and outdoor PM2.5, O3, and NO2 were monitored throughout the study and combined with time activity pattern to estimate personal air pollution exposure. The results show that a 10% increase of urinary 6-sulfatoxymelatonin (aMT6s, a major metabolite of melatonin and highly correlated with circulating melatonin) was associated with a significant increase in urinary 8-OHdG by 2.4% [95% CI: 1.4%, 3.4%] and a significant decrease in urinary free MDA and soluble P-selectin by -1.5% [-2.4%, -0.6%] and -1.0% [-1.9%, -0.1%], respectively. Compared to unadjusted models (specified in parenthesis), models with urinary aMT6s as an effect modifier showed that 10 µg/m3 in PM2.5 12h personal exposure was associated with a change in urinary 8-OHdG by 11.0% [-2.4%, 24.3%] (unadjusted: -3.8% [-7.4%, -0.2%]), a change in urinary free MDA by 14.0% [2.4%, 25.7%] (unadjusted: -0.3% [-3.4%, 2.8%]), and 10 µg/m3 increase in NO2 12h personal exposure was associated with a change in P-selectin by 5.4% [-10.2%, 21.0%] (unadjusted: -5.3% [-9.5%, -1.1%]). Similar mediation effects were also observed for O3. These findings support the role of melatonin as a mediator for oxidative stress and platelet activation introduced by air pollution exposure.