Bisphenol A increases hydrogen peroxide generation by thyrocytes both in vivo and in vitro

Abstract

Bisphenol A (BPA) is the most common monomer in polycarbonate plastics and an endocrine disruptor. Though some effects of BPA on thyroid hormone (TH) synthesis and action have been described, the impact of this compound on thyroid H2O2 generation remains elusive. H2O2 is a reactive oxygen species (ROS), which could have deleterious effect on thyrocytes if in excess. Therefore, herein we aimed at evaluating the effect of BPA exposition both in vivo and in vitro on H2O2 generation in thyrocytes, besides other essential steps for TH synthesis. Female Wistar rats were treated with vehicle (control) or BPA 40 mg/kg BW for 15 days, by gavage. We then evaluated thyroid iodide uptake, mediated by sodium-iodide symporter (NIS), thyroperoxidase (TPO) and dual oxidase (DOUX) activities (H2O2 generation). Hydrogen peroxide generation was increased, while iodide uptake and TPO activity were reduced by BPA exposition. We have also incubated the rat thyroid cell line PCCL3 with 10−9 M BPA and evaluated Nis and Duox mRNA levels, besides H2O2 generation. Similar to that found in vivo, BPA treatment also led to increased H2O2 generation in PCCL3. Nis mRNA levels were reduced and Duox2 mRNA levels were increased in BPA-exposed cells. To evaluate the importance of oxidative stress on BPA-induced Nis reduction, PCCL3 was treated with BPA in association to N-acetylcysteine, an antioxidant, which reversed the effect of BPA on Nis. Our data suggest that BPA increases ROS production in thyrocytes, what could lead to oxidative damage thus possibly predisposing to thyroid disease.

Inhibition of Type 1 Iodothyronine Deiodinase by Bisphenol A

“…Plastic EDC have been shown to disrupt the hypothalamus-pituitary-thyroid (HPT) axis, affecting the activity of key enzymes of thyroid hormone (TH) synthesis, antagonizing TH receptors (TR), as well as interfering with the binding of TH to transport proteins in plasma [10][11][12][13][14]. However, data in literature regarding the effect of plastic EDC on TH metabolism are scarce.…”

Bisphenols as Environmental Triggers of Thyroid Dysfunction: Clues and Evidence

“…It cannot be excluded that exposure of thyrocytes to BPA involves hydrogen peroxide generation due to an elevated activity of a calcium-dependent NAPDH oxidase (DUOX) [106]. TPO is a key enzyme in the synthesis of THs, catalyzing, through the cofactor H 2 O 2 , the iodination of tyrosyl residues in Tg [106].…”

“…It cannot be excluded that exposure of thyrocytes to BPA involves hydrogen peroxide generation due to an elevated activity of a calcium-dependent NAPDH oxidase (DUOX) [106]. TPO is a key enzyme in the synthesis of THs, catalyzing, through the cofactor H 2 O 2 , the iodination of tyrosyl residues in Tg [106]. Thus, the increased oxidative stress in the thyroid gland, which is related to a reduction of TPO activity, corroborates the negative correlation between TPO and DUOX2 in thyroid nodular lesions [170].…”

“…In other experiments, BPA exposure did not produce significant variations in plasma T4 levels [106][107][108][109] or, alternatively, the effects may not endure after BPA removal and metabolism [110][111][112]. It is still unclear whether exposure to BPA and its derivatives can cause hypothyroidism due to limited evidence.…”

“…Moreover, in female adult rats BPA lowered thyroid iodide uptake and thyroid peroxidase (TPO) activity, which are two essential steps in TH biosynthesis, probably due to an elevation of reactive oxygen species (ROS) production. Both NIS and TPO have been found to be sensitive to ROS [119,120], and in particular the decrease in TPO activity could be attributable to the oxidation of this enzyme [106]. Increased expression of pituitary Tshβ was reported in female rat neonates exposed to BPA [117], whereas Silva et al did not find any significant reduction of Tshβ mRNA levels in treated female rats [106].…”