Urinary phthalate metabolites in relation to biomarkers of inflammation and oxidative stress: NHANES 1999-2006

Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Environmental Research (Impact Factor: 4.37). 02/2011; 111(5):718-26. DOI: 10.1016/j.envres.2011.02.002
Source: PubMed


Phthalate esters are a class of compounds utilized extensively in widely-distributed consumer goods, and have been associated with various adverse health outcomes in previous epidemiologic research. Some of these health outcomes may be the result of phthalate-induced increases in oxidative stress or inflammation, which have been demonstrated in animal studies. The aim of this study was to explore the relationship between urinary phthalate metabolite concentrations and serum markers of inflammation and oxidative stress (C-reactive protein (CRP) and gamma glutamyltransferase (GGT), respectively). Subjects were participants in the National Health and Nutrition Examination Survey (NHANES) between the years 1999 and 2006. In multivariable linear regression models, we observed significant positive associations between CRP and mono-benzyl phthalate (MBzP) and mono-isobutyl phthalate (MiBP). There were CRP elevations of 6.0% (95% confidence interval (CI) 1.7-10.8%) and 8.3% (95% CI 2.9-14.0%) in relation to interquartile range (IQR) increases in urinary MBzP and MiBP, respectively. GGT was positively associated with mono(2-ethylhexyl) phthalate (MEHP) and an MEHP% variable calculated from the proportion of MEHP in comparison to other di(2-ethylhexyl) phthalate (DEHP) metabolites. IQR increases in MEHP and MEHP% were associated with 2.5% (95% CI 0.2-4.8%) and 3.7% (95% CI 1.7-5.7%) increases in GGT, respectively. CRP and GGT were also inversely related to several phthalate metabolites, primarily oxidized metabolites. In conclusion, several phthalate monoester metabolites that are detected in a high proportion of urine samples from the US general population are associated with increased serum markers of inflammation and oxidative stress. On the other hand, several oxidized phthalate metabolites were inversely associated with these markers. These relationships deserve further exploration in both experimental and observational studies.

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Available from: Rita Loch-Caruso, Dec 12, 2013
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    • "MEHP is the active monoester metabolite of DEHP in vivo and discharged in the urine [5]. It has been reported that in the NHANES cohort between 1999 and 2006, MEHP was found in their urine samples in about 80% participants [6], which indicated that the human DEHP exposure was universal. "
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    ABSTRACT: Mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of di-(2-ethylhexyl) phthalate (DEHP), is a widespread environmental contaminant and has been proved to have potential adverse effects on the reproductive system, carcinogenicity, liver, kidney and developmental toxicities. However, the effect of MEHP on vascular system remains unclear. The main purpose of this study was to evaluate the cytotoxic effects of MEHP on human umbilical endothelial cells (HUVEC) and its possible molecular mechanism. HUVEC cells were treated with MEHP (0, 6.25, 12.5, 25,50 and 100 µM), and the cellular apoptosis and mitochondrial membrane potential as well as intracellular reactive oxygen species were determined. In present study, MEHP induced a dose-dependent cell injury in HUVEC cell via an apoptosis pathway as characterized by increased percentage of sub-G1, activation of caspase-3, -8and -9, and increased ratio of Bax/bcl-2 mRNA and protein expression as well as cytochrome C releasing. In addition, there was obvious oxidative stress, represented by decreased glutathione level, increased malondialdehyde level and superoxide dismutase activity. N-Acetylcysteine, as an antioxidant that is a direct reactive oxygen species scavenger, could effectively block MEHP-induced reactive oxygen species generation, mitochondrial membrane potential loss and cell apoptosis. These data indicated that MEHP induced apoptosis in HUVEC cells through a reactive oxygen species-mediated mitochondria-dependent pathway.
    PLoS ONE 05/2014; 9(5):e97607. DOI:10.1371/journal.pone.0097607 · 3.23 Impact Factor
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    • "NHANES is an ongoing cross-sectional study designed to measure subject exposure to various environmental chemicals, dietary intake patterns, and various health outcomes [69]. Our previous studies indicated several associations between urinary phthalate metabolites and serum markers of oxidative stress in a large human population [70,71]. As a follow-up, this analysis examines the same association when phthalate exposure occurs in conjunction with exposure to other environmental contaminants that may also be capable of causing an oxidative stress response. "
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