Nitrated Polycyclic Aromatic Hydrocarbons and Arachidonic Acid Metabolisms Relevant to Cardiovascular Pathophysiology: Findings from a Panel Study in Healthy Adults

Abstract

Concerns on nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) in the environment have mainly arisen from their mutagenic and carcinogenic effects. The objective of this study is to investigate whether nitro-PAH exposures are associated with biomarkers of cardiovascular pathophysiology. In a panel study design, urines and blood samples were collected up to four times with a 2-week interval from 89 healthy adults. We measured 1-naphthylamine, 2-naphthylamine, 9-aminophenanthrene, 2-aminofluorene, and 1-aminopyrene as biomarkers of nitro-PAH exposures. We measured three urinary metabolites of arachidonic acid (AA) including 20-hydroxyeicosatetraenoic acid (20-HETE) from the cytochrome P450 (CYP) pathway, 8-isoprostane from the nonenzymatic pathway, and 11-dehydro-thromboxane B2 (11-dhTXB2) from the cyclooxygenase (COX) pathway. Urinary malondialdehyde, 8-hydroxy-2′-deoxyguanosine (8-OHdG), and 6-sulfatoxymelatonin (aMT6s) were measured to reflect systemic oxidative stress. Plasma concentrations of the soluble P-selectin and von Willebrand factor (vWF) were measured as biomarkers of platelet activation and endothelial dysfunction. We found that increased urinary concentrations of amino-PAHs were significantly associated with increased 20-HETE, 11-dhTXB2, and 8-OHdG and with decreased 8-isoprostane and aMT6s. Increased amino-PAHs were positively associated with P-selectin and vWF, respectively. These results suggest that exposure to nitro-PAHs increases systemic oxidative stress and alters AA metabolism toward CYP and COX pathways, leading to an increased cardiovascular disease risk.

Urinary Amino-Polycyclic Aromatic Hydrocarbons in Urban Residents: Finding a Biomarker for Residential Exposure to Diesel Traffic

“…Remarkably, we found that disease status (i.e., COPD and IHD) is significantly associated with increased urinary APAH levels. This is mechanistically supported by our recent panel studies that associated urinary APAH levels with biomarkers relevant to cardiovascular pathophysiology . Considering the exploratory nature of these findings, future efforts are needed to further clarify the cardiopulmonary effects associated with urinary APAH levels.…”

Emerging Disinfection Byproduct 2,6-Dichlorobenzoquinone-Induced Cardiovascular Developmental Toxicity of Embryonic Zebrafish and Larvae: Imaging and Transcriptome Analysis

“…Furthermore, we found that 11 upregulated genes ( cox2 , cox5b2 , cox6a1 , cox6b2 , cox6c , cox7a , cox7a2a , cox7c , cox8b , uqcrq , and uqcrh ) enriched in these three signaling pathways (cardiac muscle contraction, metabolic pathways, and oxidative phosphorylation pathway) (Figure A,C), are the cyclooxygenase (COX) subunits. A recent study reported that exposure to nitro-PAHs may increase oxidative stress, change the activity of the COX family, and adversely affect cardiovascular health . We found that DCBQ upregulated 7 genes ( al929536.3 , gstm.1 , gstm.3 , gsto2 , gstp1 , gstr , and gstt1b ) enriched in three signaling pathways: metabolic pathways, xenobiotics metabolism (cytochrome P450), and glutathione metabolism.…”

“…A recent study reported that exposure to nitro-PAHs may increase oxidative stress, change the activity of the COX family, and adversely affect cardiovascular health. 59 We found that DCBQ upregulated 7 genes (al929536. 3, gstm.1, gstm.3, gsto2, gstp1, gstr, andgstt1b) enriched in three signaling pathways: metabolic pathways, xenobiotics metabolism (cytochrome P450), and glutathione metabolism.…”

Platelet Mitochondrial DNA Methylation as Epigenetic Biomarker of Short-Term Air Pollution Exposure in Healthy Subjects

“…PAHs are important components of atmospheric aerosols, which are mostly concentrated in fine particles ( Li et al, 2016 ; He et al, 2018 ). Urinary PAHs are frequently used to estimate total exposure to PAHs ( He et al, 2021 ). Previous studies have shown that the concentration of PAHs in the air of China is high inland and low along the coast ( Li et al, 2014 ).…”