Exposure to ambient PM2.5 and its bound metals is known to have adverse health effects, particularly for subjects at high risk, including children, pregnant women, the elderly, and those with chronic cardiopulmonary diseases (Johnson et al., 2021; Korten et al., 2017; Luo et al., 2017; Qu et al., 2018; Sui et al., 2021). The effect of particulate matter on human health may not only depend on its concentration but also its chemical compositions (Liu et al., 2015; Wu et al., 2016) and oxidative potential (Daellenbach et al., 2020) in generating oxidative stress response, such as reactive oxygen species (ROS). The metal composition of particulate matter, including Fe, Cu, Cd, Hg, Ni, Pb, and As, serve as an important indicator of its effect on human health, due to their ability in disrupting the balance between oxidant and antioxidant activities. For example, a Canadian epidemiological study conducted repeated measurements on healthy adults and showed a negative association of 24-h PM2.5-V, Zn, and Cd with lung function parameters (Cakmak et al., 2014). Another cohort study from China found that urinary As was associated with decreased lung function parameters and an increased risk of restrictive respiratory disorder (Zhou et al., 2022), although conflicting evidence exists (Xu et al., 2021). These highlight the need for better understanding the metal composition of particulate matters and their health impact, as well as for developing markers of response in monitoring the exposure, which remain important issues in environmental health.

Oxidative stress can be induced by exposure to environmental pollutants and/or dysregulated endogenous antioxidants (Birben et al., 2012; Marrocco et al., 2017), resulting in subsequent alteration of lipids, sugars, proteins and nucleotides and/or activation of adaptive signaling response (Negre-Salvayre et al., 2010; Roberts et al., 2010). Consequently, increased oxidative stress response has been associated with the pathogenesis of various disease conditions, including cancer, cardiovascular disease, diabetes, arthritis, neurodegenerative disorders, and pulmonary, renal, and hepatic diseases (Zuo et al., 2019). To counteract the impact of oxidative stress response, several molecules with antioxidant activity either through non-enzymatic (e.g. glutathione etc.) or enzymatic [e.g. superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX)] mechanisms (Valko et al., 2007). Thus, measurement of oxidative stress markers from various sources has been used as markers of response and their relationship with disease conditions. For example, a cross-sectional study on workers at a coking plant in China found that PM2.5-Mn, Co, Cu, Zn, As, Cd, Pb exposure, as well as urinary levels of V, Cr, Mn, Co, Ni, Cu, Zn, As, Cd, and Pb were positively associated with urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) level (Hu et al., 2021). A longitudinal study of workers at a coking plant in Taiwan found that the high exposure group had significantly higher urinary N7-methylguanine (N7-meG) levels than the low exposure group (Chao et al., 2008). On the other hand, a study of workers exposed to diesel exhaust in an engine plant found no significant difference in the urinary 4-hydroxynonenal (4-HNE) levels compared to the control group (Bin et al., 2016). These informative, yet inconsistent, results highlight the need for better understanding of the toxic mechanism and for further research in identifying exposure-specific markers.

Previously, we have shown that increased levels of two oxidative stress markers, HEL and 4-HNE (Kato et al., 1999; Sakai et al., 2014), were noted in subjects with current asthma (Hsu et al., 2023; Wu et al., 2023), and increased levels of HEL were shown to be associated with the levels of PM2.5 exposure in both asthma cases and healthy controls. These results suggest that HEL, a marker for the initial stage of lipid peroxidation (Kato et al., 1999), may be a more sensitive marker of environmental exposure from multiple sources, including PM2.5, in both the asthma and healthy control groups. Currently, research exploring the relationship between the exposure to PM2.5-bound metals and biomarkers of DNA damage and lipid peroxidation, including 8-OHdG, N7-meG, 4-HNE, and HEL, is still limited. To this end, the current study aimed to longitudinally evaluate a battery of oxidative stress markers, antioxidants, and lung function parameters. The primary goal was to investigate their relationship with PM2.5 and its bound metals exposure in a panel of healthy participants. The objective is to identify correlated markers with the potential to serve as indicators for exposure to PM2.5 and its bound metals, thereby establishing a foundation for precision environmental health.