No 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.

Blood biomarkers of oxidative stress and inflammation have been associated with increased risk of hypertension development; yet their application in sub-Saharan Africa has been limited due to the lack of blood collection facilities. In this study, we evaluated the usefulness of dried blood spots (DBS), a more feasible alternative to venous blood, in rural sub-Saharan residents. We recruited 342 women with incident hypertension from rural Senegal, and measured C-reactive protein (CRP) and malondialdehyde (MDA) in DBS and concurrent blood pressure (BP) at baseline and 1-year follow-up. Associations of DBS biomarkers with current levels of and 1-year changes in BP were examined after adjusting for demographic, medical, and socioeconomic covariates. DBS concentrations of MDA were significantly associated with concurrent systolic BP (SBP) (p < 0.05), while DBS baseline concentrations of CRP were associated with longitudinal changes in SBP between baseline and follow-up. Compared to participants with baseline CRP < 1 mg/L, those with CRP of 1–3 mg/L and 3–10 mg/L had 2.11 mmHg (95%CI: −2.79 to 7.02 mmHg) and 4.68 mmHg (95%CI: 0.01 to 9.36 mmHg) increases in SBP at follow-up, respectively. The results support the use of DBS biomarkers for hypertension prevention and control, especially in settings with limited clinical resources.

Background: There are few oxidative biomarkers that can be used in resource-limited settings (e.g., rural Africa) where blood collection facilities are lacking. This study aims to evaluate the potential of malondialdehyde (MDA) in dried blood spots (DBS) as a useful biomarker to monitor cardiopulmonary health. Methods: We first conducted a cross-validation comparison of matched capillary DBS, plasma, and whole venous blood collected from nine healthy volunteers for the measurement of total MDA (free + conjugated) and C-reactive protein (CRP), a well-established biomarker of systemic inflammation. Then a field study was conducted in a rural Senegal with a population of 441 women routinely exposed to severe household air pollution, examining associations of MDA and CRP levels in 882 DBS with self-reported cardiopulmonary symptoms. Results: In the cross-validation study, CRP levels were strongly correlated across DBS, plasma, and whole blood. MDA levels were correlated between DBS and whole blood and were 1-2 orders of magnitude lower in plasma, suggesting that DBS MDA may reflect total oxidation levels in intracellular and extracellular compartments. In the field study, we observed significantly higher MDA levels in women with secondhand smoke exposure. An interquartile range increase in MDA concentration was associated with 27.0% (95% CI: 3.1-56.5%) and 21.1% (95% CI: −3.5% to 52.0%) increases in the incidence of chest tightness and breath difficulty, respectively. In contrast, CRP levels were not associated with worse outcomes or risk factors.Conclusions: These results support the use of DBS as a convenient alternative to venous blood when MDA is measured as a biomarker for cardiopulmonary health risk.