Metal exposure and oxidative stress markers in pregnant Navajo Birth Cohort Study participants

Abstract

Contamination of soil and water by waste from abandoned uranium mines has led to chronic exposures to metal mixtures in Native American communities. Our previous work demonstrated that community exposures to mine waste increase the likelihood of developing cardiovascular disease, as well as the likelihood of developing multiple chronic diseases including diabetes, hypertension and kidney disease. Exposure to various environmental metals is associated with elevated oxidative stress, which is considered a contributor to these and other chronic disease states. The purpose of the current research was to assess potential associations between exposure to uranium and arsenic and evidence for increased oxidative stress as measured by urinary F -isoprostanes in pregnant women enrolled in the Navajo Birth Cohort Study. The current study also included an analysis of zinc as a potential mediator of oxidative stress in the study population. Urinary arsenic and uranium, serum zinc and urinary F -isoprostanes were measured for each study participant at enrollment. Study participants were pregnant women with median age of 26.8; 18.9% were enrolled in the 1st trimester, 44.7% were enrolled in the 2nd trimester, and 36.4% were enrolled in the 3 trimester. Median urinary metal levels were 5.5 and 0.016 µg/g creatinine for arsenic and uranium, respectively. Multivariable regression analysis indicated a significant association between arsenic exposure and the lipid peroxidation product 8-iso-prostaglandin F controlling for zinc and trimester. No associations were detected with uranium despite evidence that levels were in the Navajo Birth Cohort samples were 2.3 times the median reported for women in the National Health and Nutrition Examination Survey (2011-12). Zinc was not found to have any causal mediation of the effects of the other metals on oxidative stress. The current work is consistent with other studies that have detected an association between arsenic and elevated oxidative stress. In contrast to arsenic, uranium did not appear to increase oxidative stress response in this study population. These findings are relevant to assessing the potential human impact of chronic exposure to mixed metal waste from abandoned uranium mines.

Two-step approach for assessing the health effects of environmental chemical mixtures: application to simulated datasets and real data from the Navajo Birth Cohort Study

“…We will explore more comprehensive simulation studies in future work. This exploratory analysis evaluating the relationship between the mixture metal exposures and oxidative biomarker analysis is consistent with our previous recently published article in this population [38], but expands those findings. That initial evaluation which focused on hypothesis-driven analyses of uranium, arsenic, and zinc, we have found a positive association between Arsenic and increased levels of an oxidative stress biomarker and no evidence of association between Uranium and the oxidative stress biomarker.…”

“…In our recently published article which focused on hypothesis-driven restricted set of analysis [38], we have investigated the contributions of uranium, total arsenic, arsenous (III) acid (arsenite, AsIII), dimethylarsinic acid (DMA), and zinc to the oxidative stress biomarker outcome. For this investigation, we have broadened the exposure suite to include metals detected in more than 60% of the samples described as above.…”

“…For this investigation, we have broadened the exposure suite to include metals detected in more than 60% of the samples described as above. The characteristics of the study population were described in the Additional file 1: Table S4 of our previous publication [38] and are shown in Additional file 1: Table S1. In addition to the metals, we also included other demographic variables (age, ceremonial tobacco usage, employment, enrollment trimester and BMI) previously shown to be linked to the oxidative stress outcome [38].…”

“…The characteristics of the study population were described in the Additional file 1: Table S4 of our previous publication [38] and are shown in Additional file 1: Table S1. In addition to the metals, we also included other demographic variables (age, ceremonial tobacco usage, employment, enrollment trimester and BMI) previously shown to be linked to the oxidative stress outcome [38]. The outcome variable oxidative stress biomarker is significantly different among ceremonial tobacco users vs non-users and among moms enrolled at different trimesters [38].…”

“…In addition to the metals, we also included other demographic variables (age, ceremonial tobacco usage, employment, enrollment trimester and BMI) previously shown to be linked to the oxidative stress outcome [38]. The outcome variable oxidative stress biomarker is significantly different among ceremonial tobacco users vs non-users and among moms enrolled at different trimesters [38]. The correlations between the metals are described in Additional file 1: Figure S1.…”