Multiple-metal exposure, diet, and oxidative stress in Uruguayan school children

Abstract

Oxidative stress (OS) is an important consequence of exposure to toxic metals but it is unclear to what extent low-level metal exposures contribute to OS in children. We examined the cross-sectional association between urinary concentrations of arsenic (As), cadmium (Cd), and lead (Pb) and urinary markers of OS: F₂-8α isoprostane and 8-hydroxy-2-deoxy-guanosine (8-OHdG). We also tested effect modification by dietary intakes. Of the 211 children aged 6-8 years living in Montevideo who were eligible for the study because they had at least one OS marker measured via ELISA, 143 were included in a complete-case analysis. Urinary metals were measured with inductively coupled plasma mass spectrometry (ICP-MS: Pb, Cd) and high-performance liquid chromatography online with hydride generation ICP-MS (As-metabolites); concentrations were log₂-transformed. All urinary markers were adjusted for specific gravity of urine. Two 24-h dietary recalls were conducted to estimate children's dietary intakes, including total fruit and vegetable consumption and vitamin C, zinc and fiber intake. Ordinary least square (OLS) and weighted quantile sum (WQS) regressions were used to estimate the association between metals and each OS marker as outcome. Metal exposure was generally low: median urinary As, Cd, Pb 9.6 μg/L, 0.06 μg/L and 1.9 μg/L, respectively. Median 8-isoprostane concentration was 1.1 and 8-OHdG 39.6 ng/mL. Log₂-transformed urinary As concentrations were positively associated with 8-OHdG concentrations (10.90 [3.82, 17.97]) in covariate-adjusted OLS models which also took account of exposure to Cd and Pb. In WQS, a mixture index was also associated with higher 8-OHdG (8.71 [1.12, 16.3] for each 25% increase in index value), mostly driven by As exposure. There was little evidence of effect modification by dietary antioxidants. In sum, even at low-level, As exposure is associated with detectable oxidative damage to the DNA.

Keywords: Arsenic; Child; Metals; Oxidative stress.

Figure 1

Lowess plot of the association between multi-metal exposure index (MEI) and 8-OHdG in ~7 y old Uruguayan children.

Figure 2. Association between urinary arsenic and urinary 8-OHdG concentrations in ~7 y old Uruguayan children with low and high dietary intakes

β [95% CI] derived from multi-metal, covariate-adjusted regressions modeling 8-OHdG as the dependent variable; n=143; all urinary biomarker concentrations were adjusted for specific gravity of urine (0.024) prior to analysis; urinary As concentration was log₂-transformed prior to analysis; low (black circles ●) and high dietary (gray squares ) intakes were defined as the median split for vitamin C (20.1 μg/1000 kcal/d), fiber (1.3 mg/1000 kcal/d), zinc (2.2 μg/1000 kcal/d), any fruit (105 g/d) and vegetables (5 g/d), and the nutrient-rich dietary pattern score (0.2); the fruit group includes the consumption of whole fruit, fruit salad, and fruit juices; the vegetable group includes the consumption of dark leafy, red-orange, beans/peas or other vegetables, either fresh or canned (but excludes potatoes); the nutrient-dense pattern consists of higher consumption of dark leaf and red-orange vegetables, higher consumption of eggs, beans, peas and potatoes, and reduced consumption of pasta and sauces/condiments; covariate adjustment included household possessions, household density, parent smoking (yes/no), child sex, BMI, and CRP-adjusted ferritin concentration.