Effects of butylparaben exposure on thyroid peroxidase (TPO) and type 1 iodothyronine deiodinase (D1) in female Wistar rats

Endocrine disrupting chemicals (EDCs) have been considered as one of the major contributors of growing burden of thyroid disorders across the globe, and most of these chemicals have the potential to disrupt thyroid hormones (THs) synthesis and other regulatory pathways of thyroid gland function. Butylparaben (BP), an established xenobiotic used as synthetic preservative, has not been thoroughly evaluated for its molecular mechanism of thyroid disrupting potential. We investigated the effects of BP on activity and gene expression of thyroid peroxidase (TPO) and type 1 iodothyronine deiodinase (D1) in female Wistar rats following subcutaneous exposure to BP at doses of 1, 5 and 10 mg/kg BW/day (expressed as BP1, BP5 and BP10 respectively) for 7 and 21 days. The results showed that BP1 and BP5 significantly increased serum T3/T4 ratio and TSH level, while BP10 reduced the level of T4 significantly without any apparent consequences on TSH and T3 levels. TPO activity in thyroid was significantly increased (p < 0.05) at BP1 and BP5, but BP10 treatment showed no effect like 17 beta-estradiol (E2). After 7 days of exposure, BP reduced D1 activity in kidney in a dose-dependent manner, while decrease in D1 activity was significant only after dosing with BP1 for 21 days (p < 0.05). Moreover, 7 and 21 days of BP exposure caused significant fold increase of Tpo mRNA levels in thyroid. In kidney, BP down-regulated the Dio1 gene (encodes D1) expression after 7 days, but significant fold increase was observed following 21 days of treatment. In conclusion, the present study revealed that BP exposure altered the transcriptional expression and activity of TPO and D1, where TSH reinforced possible association with TPO activity.