Acrylamide induces a thyroid allostasis-adaptive response in prepubertal exposed rats

Viviane Matoso de Oliveira; Fernanda Ivanski; Isabela Medeiros de Oliveira; Paula Bargi-Souza; Dalton Luiz Schiessel; Marco Aurelio Romano; Renata Marino Romano

doi:10.1016/j.crtox.2020.10.003

Acrylamide induces a thyroid allostasis-adaptive response in prepubertal exposed rats

Curr Res Toxicol. 2020 Oct 31:1:124-132. doi: 10.1016/j.crtox.2020.10.003. eCollection 2020 Jun 10.

Authors

Viviane Matoso de Oliveira¹, Fernanda Ivanski¹, Isabela Medeiros de Oliveira¹, Paula Bargi-Souza², Dalton Luiz Schiessel³, Marco Aurelio Romano¹, Renata Marino Romano¹

Affiliations

¹ Laboratory of Reproductive Toxicology, Department of Medicine, State University of Central-West, Rua Simeao Camargo Varela de Sa, 03, 85040-080 Parana, Brazil.
² Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Avenida Presidente Antônio Carlos, 6627, 31270-901 Minas Gerais, Brazil.
³ Department of Nutrition, State University of Central-West, Rua Simeao Camargo Varela de Sa, 03, 85040-080 Parana, Brazil.

Abstract

Some endocrine-disrupting chemicals (EDCs) can affect the endocrine system through covalent interactions with specific sites, leading to deregulation of physiological homeostasis. The acrylamide (AA) present in some fried or baked foods is an example of an electrophile molecule that is able to form adducts with nucleophilic regions of nervous system proteins leading to neurological defects. A positive correlation between increased urinary AA metabolite concentration and reduced levels of thyroid hormones (TH) was described in adolescents and young adults. Thus, this study aimed to evaluate whether AA affects the physiology of the hypothalamus-pituitary-thyroid (HPT) axis and the possible repercussions in peripheral TH-target systems. For this, male Wistar rats were exposed to doses of 2.5 or 5.0 mg AA/Kg/day, based on the LOAEL (Lowest Observed Adverse Effect Level) during prepubertal development. The expression of molecular markers of HPT functionality was investigated in the hypothalamus, pituitary, thyroid, heart and liver, as well as the hormonal and lipid profiles in blood samples. Herein, we showed that AA acts as EDCs for thyroid gland function, increasing the transcript expression of several proteins related to TH synthesis and altering hypothalamus-pituitary-thyroid axis homeostasis, an effect evidenced by the higher levels of THs in the serum. Compensatory mechanisms were observed in TH-target tissues, such as an increase in Dio3 mRNA expression in the liver and a reduction in Mct8 transcript content in the hearts of AA-treated rats. Together, these results pointed out an allostatic regulation of the HPT axis induced by AA and suggest that chronic exposure to it, mainly associated with food consumption, might be related to the higher prevalence of thyroid dysfunctions.

Keywords: AA, acrylamide; Acrylamide; BW, body weight; DIO1, iodothyronine deiodinase 1; DIO2, iodothyronine deiodinase 2; DIO3, iodothyronine deiodinase 3; EDCs, endocrine-disrupting chemicals; Endocrine-disrupting chemicals; HDL, high-density lipoproteins; HPT, hypothalamus-pituitary-thyroid axis; LDL, low lipoproteins; LOAEL, lowest Observed Adverse Effect Level; MCT-8, monocarboxylate transporter 8; MYH6, myosin heavy chain 6; NIS, sodium/iodide symporter; NOAEL, no Observed Adverse Effect Level; PDS, pendrin; PND, postnatal day; RfD, reference dose; T3, triiodothyronine; T4, thyroxine; TDI, tolerable daily intake; TH, thyroid hormones; THRA1, thyroid hormone receptor alpha 1; THRB2, thyroid hormone receptor beta 2; TPO, thyroid peroxidase; TRH, thyrotropin releasing hormone hormone; TRHR, thyrotropin releasing hormone receptor; TSH, thyroid hormone receptor; TSH, thyrotropin; Thyroid; Thyroid hormone metabolism.