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A comparative genotoxicity study of a supraphysiological dose of triiodothyronine (T₃) in obese rats subjected to either calorie-restricted diet or hyperthyroidism.

De Sibio MT, Luvizotto RA, Olimpio RM, Corrêa CR, Marino J, de Oliveira M, Conde SJ, Ferreira AL, Padovani CR, Nogueira CR - PLoS ONE (2013)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Botucatu Medical School - University of Sao Paulo State (UNESP), Botucatu, SP, Brazil. mt_bio@yahoo.com.br

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.

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Experimental protocol. Control (C, n = 10); obese (OB, n = 50), obese given T3 at 25 µg/100 g BW (OS, n = 10), calorie-restricted obese (OR, n = 10) and calorie-restricted obese given T3 at 25 µg/100 g BW (ORS, n = 10).
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pone-0056913-g001: Experimental protocol. Control (C, n = 10); obese (OB, n = 50), obese given T3 at 25 µg/100 g BW (OS, n = 10), calorie-restricted obese (OR, n = 10) and calorie-restricted obese given T3 at 25 µg/100 g BW (ORS, n = 10).

Mentions: Sixty-five male Wistar rats (aged 60 days and weighing approx. 150 g) were assigned for this experiment, and they were supplied by the animal facility of the Experimental Laboratory for Internal Medicine at the “Júlio de Mesquita Filho” Universidade Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil. In accordance with our selection criteria [7], 15 animals excluded from the experiments. Animals were housed in individual cages under controlled room temperature (22–26°C) and lighting (12 h light/dark cycle). Animals were initially divided into two groups: control animals (C, n = 10) receiving standard food (RC Focus 1765, Agroceres®, Rio Claro, São Paulo, Brazil) containing 12.3% calories from fat and 2.95 kcal/g, and obese animals (OB, n = 40) fed a hypercaloric diet (RC Focus 2413, Agroceres®, Rio Claro, São Paulo, Brazil) containing 49.2% calories from fat and 3.65 kcal/g, as previously described [7] for 20 weeks to induce obesity. The composition of the diets is given in Table 1[7]. After this period, 20 OB animals continued on the hypercaloric diet, whereas the other 20 formed a new group (OR) that was submitted to calorie restriction. The group then underwent calorie restriction, wherein it was placed on a normocaloric diet with 75% of the quantity ingested by the control group [8], for 8 weeks. Thus, the restriction applied was 25% of the control group. Afterwards, ten OB and ten OR animals received a supraphysiological dose of T3 (25 µg/100 g animal body weight) [9] for 2 weeks, as shown in Figure 1. On week 30, rats were killed by decapitation, and blood was collected and kept at -80 C for further analysis. The Botucatu Medical School Commission for Ethics in Animal Experimentation at UNESP approved the study designated experimental protocol No. 648.


A comparative genotoxicity study of a supraphysiological dose of triiodothyronine (T₃) in obese rats subjected to either calorie-restricted diet or hyperthyroidism.

De Sibio MT, Luvizotto RA, Olimpio RM, Corrêa CR, Marino J, de Oliveira M, Conde SJ, Ferreira AL, Padovani CR, Nogueira CR - PLoS ONE (2013)

Experimental protocol. Control (C, n = 10); obese (OB, n = 50), obese given T3 at 25 µg/100 g BW (OS, n = 10), calorie-restricted obese (OR, n = 10) and calorie-restricted obese given T3 at 25 µg/100 g BW (ORS, n = 10).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585230&req=5

pone-0056913-g001: Experimental protocol. Control (C, n = 10); obese (OB, n = 50), obese given T3 at 25 µg/100 g BW (OS, n = 10), calorie-restricted obese (OR, n = 10) and calorie-restricted obese given T3 at 25 µg/100 g BW (ORS, n = 10).
Mentions: Sixty-five male Wistar rats (aged 60 days and weighing approx. 150 g) were assigned for this experiment, and they were supplied by the animal facility of the Experimental Laboratory for Internal Medicine at the “Júlio de Mesquita Filho” Universidade Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil. In accordance with our selection criteria [7], 15 animals excluded from the experiments. Animals were housed in individual cages under controlled room temperature (22–26°C) and lighting (12 h light/dark cycle). Animals were initially divided into two groups: control animals (C, n = 10) receiving standard food (RC Focus 1765, Agroceres®, Rio Claro, São Paulo, Brazil) containing 12.3% calories from fat and 2.95 kcal/g, and obese animals (OB, n = 40) fed a hypercaloric diet (RC Focus 2413, Agroceres®, Rio Claro, São Paulo, Brazil) containing 49.2% calories from fat and 3.65 kcal/g, as previously described [7] for 20 weeks to induce obesity. The composition of the diets is given in Table 1[7]. After this period, 20 OB animals continued on the hypercaloric diet, whereas the other 20 formed a new group (OR) that was submitted to calorie restriction. The group then underwent calorie restriction, wherein it was placed on a normocaloric diet with 75% of the quantity ingested by the control group [8], for 8 weeks. Thus, the restriction applied was 25% of the control group. Afterwards, ten OB and ten OR animals received a supraphysiological dose of T3 (25 µg/100 g animal body weight) [9] for 2 weeks, as shown in Figure 1. On week 30, rats were killed by decapitation, and blood was collected and kept at -80 C for further analysis. The Botucatu Medical School Commission for Ethics in Animal Experimentation at UNESP approved the study designated experimental protocol No. 648.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Botucatu Medical School - University of Sao Paulo State (UNESP), Botucatu, SP, Brazil. mt_bio@yahoo.com.br

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.

Show MeSH
Related in: MedlinePlus