| Animal Admin |
Mice[2] One hundred eighteen male C57BL/6 mice, 3 months old, are kept in standardized conditions with free access to water and normal chow. 3,5,3′-triiodo-L-thyronine (T3) or Sobetirome is administered i.p. in 20% DMSO or propylene glycol for 8 days, once daily at 9:00 a.m.; controls receive vehicle. In one experiment, nine groups of six mice are treated with vehicle, or 5.4, 24, 48, and 97 nmol/kg per day of T3 or Sobetirome. The lowest dose of T3 induces euthyroidism in hypothyroid mice. In another experiment, one group of seven mice is given no additional supplementation; three groups of seven mice receive 10% corn oil and 2% cholesterol (cholesterol diet); and three groups of seven mice receive 10% corn oil, 2% cholesterol, and 0.5% cholic acid (cholic acid diet). For this experiment, mice are treated with vehicle or 97 nmol/kg per day Sobetirome or T3. Food is withdrawn 5 h before kill. Blood is drawn by cardiac puncture under light isoflurane anesthesia. Animals are killed by cervical dislocation. Livers are immediately frozen in liquid nitrogen. For analysis of bile acid excretion, three groups of five chow-fed mice are treated with vehicle, 48 nmol/kg per day of Sobetirome, or T3 for 5 days. Feces are collected group-wise 24 h before treatment and in the last 24 h of the experiment. Rats[3] Female Wistar rats are randomly divided into five groups (n=8 per group): (i) control, treated with saline; (ii) 10× T3, treated with 3 μg T3/100 g body weight (BW) per day, which is equivalent to ten times the physiological dose of T3; (iii) 20× T3, treated with double of the previous T3 dosage (6 μg T3/100 g body weight (BW) per day); (iv) 10× Sobetirome, treated with 1.5 μg Sobetirome/100 g BW per day and (v) 20× Sobetirome, treated with 3 μg Sobetirome/100 g BW per day. The latter two groups are treated with Sobetirome in equimolar doses of 10× T3 and 20× T3 respectively. The equimolar doses of Sobetirome are calculated from the molecular mass of T3 (mol mass=651) and Sobetirome (mol mass=328.4). T3 is dissolved in 40 mM NaOH, and Sobetirome is dissolved in DMSO to a concentration of 1 mg/mL; either T3 or Sobetirome are then diluted in saline and administered i.p. every day for 6 weeks. BW is measured thrice a week. Body length (nose to base of the tail) is determined at the end of the experimental period.
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