The Effect of Urinary Polycyclic Aromatic Hydrocarbon Metabolites on Lipid Profiles: Does Oxidative Stress Play a Crucial Mediation Role?

Abstract

Urinary polycyclic aromatic hydrocarbon (PAH) metabolites are associated with oxidative stress; however, epidemiological studies have not reported the impacts of these urinary PAH metabolites on blood lipid levels. This study investigated the relationship between urinary PAH metabolites, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and blood lipid profiles. A total of 109 elderly volunteers were recruited with complete datasets for analysis. Blood and morning urine samples were collected in the winter of 2011. The PAH metabolites, creatinine, and 8-OHdG levels in urine samples were analyzed using Gas Chromatography-Mass Spectrometry, spectrophotometry, and an ELISA kit, respectively. The blood lipid profiles were analyzed using an automatic biochemical analyzer. The relationship between lipid profiles and 8-OHdG was assessed using a two-independent sample nonparametric test, categorized by gender, smoking, and alcohol consumption status. After normalizing the concentration values, a general linear regression model was employed to examine the correlations between PAH metabolites, 8-OHdG, and lipid profiles. A mediation model was developed to investigate the mediating effect of 8-OHdG on the relationship between PAH metabolites and lipid profiles. The median of eight PAH metabolite concentrations in urine samples ranged from 1 to 10 μmol/mol creatinine (Cr). Significant differences in lipid profiles were observed across genders. However, no significant differences were found in smoking or alcohol consumption status for both genders. Linear regression analysis revealed that an increase in the logarithmic concentration of 2-hydroxynaphthalene (2-OHNap), 9-hydroxyfluorene (9-OHFlu), 3-hydroxyfluorene (3-OHFlu), 2-hydroxyfluorene (2-OHFlu), 1-hydroxypyrene (1-OHPyr), and 6-hydroxychrysene (6-OHChr) was associated with an increase in urinary 8-OHdG levels, after adjusting for BMI and age. Specifically, 1-hydroxynaphthalene (1-OHNap) and 1-OHPyr correlated negatively with apolipoprotein A1 (Apo A1). Conversely, 1-OHPyr was positively correlated with low-density lipoprotein cholesterol (LDL-C). In addition, b,c-dihydroxyphenanthrene (2-OHBcPhe) was positively associated with apolipoprotein B (Apo B). Notably, 8-OHdG did not exhibit a significant correlation with lipid profiles. The mediating effect of 8-OHdG on the relationship between hydroxylated PAHs and lipid profiles was not statistically significant. However, the indirect effects of hydroxylated PAHs on blood lipids were statistically substantial, specifically for 1-OHNap to Apo A1 (-0.025, 95% CI: -0.041, -0.009), 1-OHPyr to LDL-C (0.107, 95% CI: 0.011, 0.203), and 2-OHBcPhe to Apo B (0.070, 95% CI: 0.005, 0.135). This study suggests that an increase in urinary PAH metabolites may elevate the levels of urinary 8-OHdG and influence blood lipid profiles. However, no direct relationship was found between 8-OHdG and lipid profiles. The mediation analysis indicated that the effects of PAH metabolites on lipid changes may operate through pathways other than oxidative stress.