Academic journal article Environmental Health Perspectives

Urine Arsenic and Arsenic Metabolites in U.S. Adults and Biomarkers of Inflammation, Oxidative Stress, and Endothelial Dysfunction: A Cross-Sectional Study

Academic journal article Environmental Health Perspectives

Urine Arsenic and Arsenic Metabolites in U.S. Adults and Biomarkers of Inflammation, Oxidative Stress, and Endothelial Dysfunction: A Cross-Sectional Study

Article excerpt

Introduction

Worldwide, an estimated 200 million individuals are exposed to water arsenic (As) concentrations exceeding the 10-[micro]g/L guideline set by the World Health Organization (WHO) (2011). Arsenic is an established human carcinogen that has also been associated with a growing number of noncancer outcomes (NRC 2013). In particular, chronic As exposure has been positively associated with cardiovascular disease (CVD) (Farzan et al. 2015a; James et al. 2015; Moon et al. 2013; reviewed in NRC 2013; Moon et al. 2012). Although the majority of research on As and CVD has been conducted in populations exposed to relatively high As levels, such as in Bangladesh, where concentrations typically exceed the country's national drinking-water standard of 50 [micro]g/L, recent evidence suggests that low to moderate As exposure may be associated with CVD-related morbidity (Gong and O'Bryant 2012; James et al. 2015; Monrad et al. 2017; Moon et al. 2013; Mordukhovich et al. 2009) and mortality (D'Ippoliti et al. 2015; Farzan et al. 2015a; Medrano et al. 2010).

Arsenic-induced CVD may be mediated by increased inflammation and oxidative stress, which adversely affect vascular endothelial function. This inference has been supported by both experimental and epidemiological studies (Burgess et al. 2013; Chen et al. 2007; Engstrom et al. 2010; Kurzius-Spencer et al. 2016; Lemaire et al. 2015; Ma et al. 2012; Mo et al. 2011; Soucy et al. 2005; Wu et al. 2012, 2014). However, the majority of existing studies utilized high doses of As or evaluated populations exposed to relatively high As concentrations, such as populations in Bangladesh (Chen et al. 2007; Wu et al. 2012). In the United States, most water As concentrations typically fall in the low to moderate range, but higher levels of contamination (>100 [micro]g/L) have been documented, including in parts of Maine and New Hampshire (Flanagan et al. 2014; USGS 2010). In New Hampshire, 40% of households depend on private wells, and >10% of these wells contain water As concentrations >10 [micro]g/L (Karagas et al. 1998).

We previously reported that low to moderate As exposure is associated with increased CVD-related mortality among long-term smokers in the New Hampshire Health Study (NHHS) (Farzan et al. 2015a). The goal of the present project was to evaluate whether As exposure is associated with biomarkers of inflammatory processes, endothelial dysfunction, and oxidative stress that may reflect pathogenic mechanisms relevant to CVD (Mozos et al. 2017; Poredos and Jezoovnik 2015), including plasma matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-[alpha] (TNF-[alpha]), plasminogen activator inhibitor-1 (PAI-1), soluble vascular and intercellular adhesion molecules (VCAM-1 and ICAM-1, respectively), and urinary 15-[F.sub.2t]-isoprostane (15-[F.sub.2t]-IsoP), which to our knowledge has not been evaluated previously in relation to As exposure, in the NHHS. We also evaluated whether the percentages of uAs metabolites are differentially associated with these biomarkers because a reduced capacity to fully metabolize inorganic As (iAs) has been associated with many As-related health outcomes (Steinmaus et al. 2010), including CVD (Chen et al. 2013b). Given the increasing evidence that susceptibility to As toxicity may differ by sex (NRC 2013), we also explored potential differences between men and women.

Methods

Participants

Participants in the present study were controls selected as part of a population-based case-control study of keratinocyte cancer in U.S. adults residing in New Hampshire (Gilbert-Diamond et al. 2013). Controls were randomly selected from population lists provided by a) the New Hampshire Department of Transportation for participants <65 y old and b) Medicaid and Medicare Services for participants [greater than or equal to] 65 y old and frequency-matched to keratinocyte cancer case distribution on sex and age. …

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