Stephani S Kim1, John D Meeker2, Alexander P Keil3, Max T Aung2, Paige A Bommarito4, David E Cantonwine5, Thomas F McElrath5, Kelly K Ferguson6. 1. Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. 2. Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA. 3. Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. 4. Department of Environmental Science and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. 5. Division of Maternal-Fetal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 6. Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. Electronic address: kelly.ferguson2@nih.gov.
Abstract
BACKGROUND: Exposure to some toxic metals, such as lead and cadmium, has been associated with increased oxidative stress. However less is known about other metals and metal mixtures, especially in pregnant women who are a vulnerable population. METHODS: To study the relationship between exposure to trace metals and oxidative stress, we analyzed a panel of 17 metals and two oxidative stress biomarkers (8-isoprostane and 8-hydroxydeoxyguanosine [8-OHdG]) in urine samples collected at ~26 weeks gestation from pregnant women in Boston (n = 380). We used linear regression models to calculate percent differences and 95% confidence intervals (CI) in oxidative stress markers for an interquartile range (IQR) increase in each urinary metal with adjustment for other metals. In addition, we applied principal components analysis (PCA) and Bayesian kernel machine regression (BKMR), to examine cumulative effects (within correlated groups of exposures as well as overall) and interactions. RESULTS: We estimated 109% (95% CI: 47, 198) higher 8-isoprostane and 71% (95% CI: 45, 102) higher 8-OHdG with an IQR increase in urinary selenium (Se). We also estimated higher 8-isoprostane (47%, 95% CI: 20.5, 79.4) and 8-OHdG (15.3%, 95% CI: 5.09, 26.5) in association with urinary copper (Cu). In our PCA, we observed higher 8-isoprostane levels in association with the "essential" PC (highly loaded by Cu, Se, and Zinc). In BKMR analyses, we also estimated higher levels of both oxidative stress biomarkers with increasing Se and Cu as well as increasing levels of both oxidative stress biomarkers in association with cumulative concentrations of urinary trace metals. CONCLUSION: We observed higher 8-isoprostane and 8-OHdG levels in association with urinary trace metals and elements, particularly Se and Cu, in linear models and using mixtures approaches. Additionally, increasing cumulative exposure to urinary trace metals was associated with higher levels of both oxidative stress biomarkers. The beneficial effects of these compounds should be carefully questioned. Published by Elsevier Inc.
BACKGROUND: Exposure to some toxic metals, such as lead and cadmium, has been associated with increased oxidative stress. However less is known about other metals and metal mixtures, especially in pregnant women who are a vulnerable population. METHODS: To study the relationship between exposure to trace metals and oxidative stress, we analyzed a panel of 17 metals and two oxidative stress biomarkers (8-isoprostane and 8-hydroxydeoxyguanosine [8-OHdG]) in urine samples collected at ~26 weeks gestation from pregnant women in Boston (n = 380). We used linear regression models to calculate percent differences and 95% confidence intervals (CI) in oxidative stress markers for an interquartile range (IQR) increase in each urinary metal with adjustment for other metals. In addition, we applied principal components analysis (PCA) and Bayesian kernel machine regression (BKMR), to examine cumulative effects (within correlated groups of exposures as well as overall) and interactions. RESULTS: We estimated 109% (95% CI: 47, 198) higher 8-isoprostane and 71% (95% CI: 45, 102) higher 8-OHdG with an IQR increase in urinary selenium (Se). We also estimated higher 8-isoprostane (47%, 95% CI: 20.5, 79.4) and 8-OHdG (15.3%, 95% CI: 5.09, 26.5) in association with urinary copper (Cu). In our PCA, we observed higher 8-isoprostane levels in association with the "essential" PC (highly loaded by Cu, Se, and Zinc). In BKMR analyses, we also estimated higher levels of both oxidative stress biomarkers with increasing Se and Cu as well as increasing levels of both oxidative stress biomarkers in association with cumulative concentrations of urinary trace metals. CONCLUSION: We observed higher 8-isoprostane and 8-OHdG levels in association with urinary trace metals and elements, particularly Se and Cu, in linear models and using mixtures approaches. Additionally, increasing cumulative exposure to urinary trace metals was associated with higher levels of both oxidative stress biomarkers. The beneficial effects of these compounds should be carefully questioned. Published by Elsevier Inc.
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