National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Safety, Health and Environmental Engineering, National United University, Miaoli, Taiwan.
National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan.
Environ Int. 2020 Jul;140:105751. doi: 10.1016/j.envint.2020.105751. Epub 2020 Apr 27.
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-NOGua) and five serum thyroid hormones (thyroxine [T], free T, 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 (β = 0.253, 95%CI [0.060, 0.447]; β = 0.317, 95% CI [0.098, 0.536]; P = 0.005) and 8-NOGua (β = -0.010, 95%CI [-0.138, 0.118]; β = 0.144, 95% CI [-0.001, 0.289]; P = 0.045). Mono-n-butyl phthalate (MnBP) was positively associated with 8-NOGua (β = 0.201, 95% CI [0.078, -0.324]; β = 0.161, 95% CI [0.031, -0.292]; P = 0.018). T was negatively associated with MDA (β = -0.027, 95% CI [-0.088, 0.0034]; β = -0.094, 95% CI [-0.161, -0.028]; P = 0.005) and 8-NOGua (β = -0.068, 95% CI [-0.127, -0.010]; β = -0.125, 95% CI [-0.184, -0.066]; P < 0.001). Free T was positively associated with MDA (P = 0.047) and with 8-NOGua (P < 0.001). 8-NOGua mediated 11% of the association between the sum of DEHP metabolites and T, and 17% of the association between MnBP and free T. These results suggest that phthalate exposure may influence thyroid hormone levels through induced oxidative/nitrosative stress.
邻苯二甲酸酯暴露被证明会改变甲状腺功能，但目前尚不清楚氧化应激和氮氧化物应激是否解释了中间的生物学机制。本研究旨在探讨成年人中邻苯二甲酸酯暴露、氧化/氮氧化物应激与甲状腺功能之间的关联，并检验氧化/氮氧化物应激在邻苯二甲酸酯暴露与甲状腺功能之间的关联中的中介作用。在 266 名台湾成年人中测量了 11 种尿邻苯二甲酸酯代谢物、3 种尿氧化/氮氧化物应激生物标志物（丙二醛 [MDA]、8-OHdG 和 8-NOGua）和 5 种血清甲状腺激素（甲状腺素 [T]、游离 T、三碘甲状腺原氨酸、促甲状腺激素和甲状腺素结合球蛋白）。使用多元回归模型分析了邻苯二甲酸代谢物、氧化/氮氧化物应激生物标志物和甲状腺激素之间的横断面关联。进行中介分析以评估氧化/氮氧化物应激在邻苯二甲酸代谢物与甲状腺激素水平之间的关联中的作用。二-（2-乙基己基）邻苯二甲酸酯（DEHP）代谢物总和与 MDA 呈正相关（β=0.253，95%CI [0.060，0.447]；β=0.317，95%CI [0.098，0.536]；P=0.005）和 8-NOGua（β=-0.010，95%CI [0.138，0.118]；β=0.144，95%CI [0.001，0.289]；P=0.045）。单正丁基邻苯二甲酸酯（MnBP）与 8-NOGua 呈正相关（β=0.201，95%CI [0.078，-0.324]；β=0.161，95%CI [0.031，-0.292]；P=0.018）。T 与 MDA 呈负相关（β=-0.027，95%CI [-0.088，0.0034]；β=-0.094，95%CI [-0.161，-0.028]；P=0.005）和 8-NOGua（β=-0.068，95%CI [-0.127，-0.010]；β=-0.125，95%CI [-0.184，-0.066]；P<0.001）。游离 T 与 MDA 呈正相关（P=0.047），与 8-NOGua 呈正相关（P<0.001）。DEHP 代谢物总和与 T 之间的 11%的关联和 MnBP 与游离 T 之间的 17%的关联通过 8-NOGua 进行中介。这些结果表明，邻苯二甲酸酯暴露可能通过诱导氧化/氮氧化物应激来影响甲状腺激素水平。
