A Comparative Genotoxicity Study of a Supraphysiological Dose of Triiodothyronine (T3) in Obese Rats Subjected to Either Calorie-Restricted Diet or Hyperthyroidism

Abstract

This study was designed to determine the genotoxicity of a supraphysiological dose of triiodothyronine (T3) in both obese and calorie-restricted obese animals. Fifty male Wistar rats were randomly assigned to one of the two following groups: control (C; n = 10) and obese (OB; n = 40). The C group received standard food, whereas the OB group was fed a hypercaloric diet for 20 weeks. After this period, half of the OB animals (n = 20) were subjected to a 25%-calorie restriction of standard diet for 8 weeks forming thus a new group (OR), whereas the remaining OB animals were kept on the initial hypercaloric diet. During the following two weeks, 10 OR animals continued on the calorie restriction diet, whereas the remaining 10 rats of this group formed a new group (ORS) given a supraphysiological dose of T3 (25 µg/100 g body weight) along with the calorie restriction diet. Similarly, the remaining OB animals were divided into two groups, one that continued on the hypercaloric diet (OB, n = 10), and one that received the supraphysiological dose of T3 (25 µg/100 g body weight) along with the hypercaloric diet (OS, n = 10) for two weeks. The OB group showed weight gain, increased adiposity, insulin resistance, increased leptin levels and genotoxicity; T3 administration in OS animals led to an increase in genotoxicity and oxidative stress when compared with the OB group. The OR group showed weight loss and normalized levels of adiposity, insulin resistance, serum leptin and genotoxicity, thus having features similar to those of the C group. On the other hand, the ORS group, compared to OR animals, showed higher genotoxicity. Our results indicate that regardless of diet, a supraphysiological dose of T3 causes genotoxicity and potentiates oxidative stress.

Integrated Stress Response Signaling Pathways Induced by Supraphysiological Concentrations of Thyroid Hormone Inhibit Viral Replication

“…Although SPCs of T3 have been used in the treatment of chronic fatigue syndrome, 29 prophylaxis-resistant psychiatric illnesses, [30][31][32] and obesity, 33,34 the mechanism of T3 action at such concentrations is not known. Here, we focused our study on the role of SPCs of T3 in modulating cellular stress signaling pathways and stress-mediated antiviral responses.…”

“…24 An earlier report has indicated that thyroid hormone receptor (THR) agonist triiodo-l-thyronine (T3) at physiological concentrations can potentiate the inhibition of vesicular stomatitis virus (VSV) replication by IFN-g; 28 however, these authors did not observe any inhibition of VSV replication by T3 alone. Although supraphysiological concentrations (SPCs) of T3 have been used in the treatment of chronic fatigue syndrome, 29 prophylaxis-resistant psychiatric illnesses, [30][31][32] and obesity, 33,34 the mechanism of T3 function at SPCs and their role in modulating cellular stress pathways and stress-mediated antiviral responses are unknown. In this paper, we report that T3 hormone at SPCs activates ISR pathways that include PKR activation, SG formation, and activation of ER-mediated stress pathways.…”

Potensi Suplementasi Resveratrol dalam Mengatasi Efek Negatif Hormon Tiroid pada Terapi Obesitas: Uji Preklinik

“…Hormon tiroid juga tidak memperbaiki resistensi insulin yang terjadi pada obesitas. 5 Oleh karena terjadi stres oksidatif yang merupakan efek negatif dari hormon tiroid, kemudian menimbulkan suatu pemikiran bahwa pemberian antioksidan eksogen itu diharapkan dapat mengurangi efek negatif hormon tiroid. Resveratrol merupakan suatu senyawa polifenol alami dan merupakan salah satu antioksidan yang juga dikenal mempunyai efek antiobesitas dan juga anti-inflamasi.…”

“…HT3 (25 mg/100 mgBB/hari) dan RSV (100 mg/kgBB/hari) 5,8 diberikan per oral selama 14 hari. Pada periode perlakuan ini diet yang diberikan kembali diet standar.…”

Triiodothyronine and breast cancer

“…However an uncontrolled study of 3,3′-diiodothyronine (3,3′-T2), iodothyronines as T3 and T4, administration to humans for 4 weeks by an unspecified route was associated with increased metabolic rate and reduced body weight [14] , no specific role of 3,3′-T2 in humans has been demonstrated [15] . Animal studies, however, suggest that the 3,5-diiodothyronine and 3,3′-T2 increase metabolic rate [15,16] , by acting at the mitochondrial level to increase hepatic cytochrome oxidase activity [17] and supraphysiological dose of T3 causes genotoxicity and potentiates oxidative stress [18] . T3 can influence the mammary gland; this involves the activation of TR present in the mammary gland inducing differentiation and lobular growth in an estrogenlike manner.…”