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

Abstract

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.

Keywords

• Mediation analysis
• Phthalates
• Thyroid hormones
• Oxidative stress
• Nitrosative stress