University of Oulu

Huang, P.-C., Waits, A., Chen, H.-C., Chang, W.-T., Jaakkola, J. J. K., & Huang, H.-B. (2020). Mediating role of oxidative/nitrosative stress biomarkers in the associations between phthalate exposure and thyroid function in Taiwanese adults. Environment International, 140, 105751.

Mediating role of oxidative/nitrosative stress biomarkers in the associations between phthalate exposure and thyroid function in Taiwanese adults

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Author: Huang, Po-Chin1,2,3,4; Waits, Alexander1; Chen, Hsin-Chang5;
Organizations: 1National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan
2Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
3Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
4Department of Safety, Health and Environmental Engineering, National United University, Miaoli, Taiwan
5Institute of Food Safety and Health, National Taiwan University, Taipei, Taiwan
6Center for Environmental and Respiratory Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland
7Medical Research Center, University of Oulu and Oulu University Hospital, Oulu, Finland
8School of Public Health, National Defense Medical Center, Taipei, Taiwan
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.3 MB)
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Language: English
Published: Elsevier, 2020
Publish Date: 2020-08-14


Phthalate exposure was shown to alter thyroid function, however it is unclear, whether oxidative and nitrosative stress explains the intermediate biological mechanism. This study aimed to investigate the associations between phthalate exposure, oxidative/nitrosative stress, and thyroid function in adults, and to examine the mediating role of oxidative/nitrosative stress in the associations between phthalate exposure and thyroid function. Levels of eleven urinary phthalate metabolites, three urinary biomarkers of oxidative/nitrosative stress (malondialdehyde [MDA], 8-OHdG, and 8-NO₂Gua) and five serum thyroid hormones (thyroxine [T₄], free T₄, triiodothyronine, thyroid-stimulating hormone, and thyroxine-binding globulin) were measured in 266 Taiwanese adults. Cross-sectional associations between phthalate metabolites, biomarkers of oxidative/ nitrosative stress and thyroid hormones were analyzed using multivariate regression models. Mediation analysis was conducted to assess the role of oxidative/nitrosative stress in the associations between phthalate metabolites and thyroid hormone levels. Sum of di-(2-ethylhexyl) phthalate (DEHP) metabolites was positively associated with MDA (βT1−T2 = 0.253, 95%CI [0.060, 0.447]; β ≧T2 = 0.317, 95% CI [0.098, 0.536]; Ptrend = 0.005) and 8-NO₂Gua (βT1−T2 = −0.010, 95%CI [−0.138, 0.118]; β ≧T2 = 0.144, 95% CI [−0.001, 0.289]; Ptrend = 0.045). Mono-n-butyl phthalate (MnBP) was positively associated with 8-NO₂Gua (βT1−T2 = 0.201, 95% CI [0.078, −0.324]; β ≧T2 = 0.161, 95% CI [0.031, −0.292]; Ptrend = 0.018). T4 was negatively associated with MDA (βT1−T2 = −0.027, 95% CI [−0.088, 0.0034]; β≧T2 = −0.094, 95% CI [−0.161, −0.028]; Ptrend = 0.005) and 8-NO₂Gua (βT1−T2 = −0.068, 95% CI [−0.127, −0.010]; β≧T2 = −0.125, 95% CI [−0.184, −0.066]; Ptrend < 0.001). Free T₄ was positively associated with MDA (Ptrend = 0.047) and with 8-NO₂Gua (Ptrend < 0.001). 8-NO₂Gua mediated 11% of the association between the sum of DEHP metabolites and T₄, and 17% of the association between MnBP and free T₄. These results suggest that phthalate exposure may influence thyroid hormone levels through induced oxidative/nitrosative stress.

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Series: Environment international
ISSN: 0160-4120
ISSN-E: 1873-6750
ISSN-L: 0160-4120
Volume: 140
Article number: 105751
DOI: 10.1016/j.envint.2020.105751
Type of Publication: A1 Journal article – refereed
Field of Science: 3142 Public health care science, environmental and occupational health
Funding: We would like to extend thanks to the National Health Research Institutes for their financial support (Grant No.: EM-107-PP-12, EM-108-PP-12, EM-109-PP-11), Ministry of National Defense Medical Affairs Bureau (MAB-109-072), and Ministry of Science of Technology (Grant No.: MOST 106-3114-B-400-001 and MOST 108-2314-B-400-039).
Copyright information: © 2020 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (