Effect of the antioxidant TK 12627 (Irganox) on monodeiodination and on the levels of messenger ribonucleic acid of 5'-deiodinase type I and spot 14.

Until now, most potent inhibitors of monodeiodination are iodinated, propylthiouracil being an exception. We report here studies on a new non-iodinated substance, triethylene glycol bis-3-(3-tert-butyl-4-hydroxy-5-methyl-phenyl) propionate (TK 12627 or Irganox), which is used as a very efficient antioxidant in the chemistry of plastics. The studies were performed with 23 hypothyroid rats that received Irganox in their daily food (8 mg.day-1 x (100 g body wt)-1) for 3 weeks. Thyroxine (T4) metabolism was studied by implanting minipumps delivering 2.3 nmol T4.day-1 x (100 g body wt)-1 for 1 week. On day 1 before sacrifice, another minipump containing [125I]-3,5,3'-triiodothyronine (T3, 2.6 microCi/day) and [131I]-3,3',5'-triiodothyronine (rT3, 2.1 microCi/day) was implanted. The results showed that with Irganox treatment serum T4 concentrations were higher (p < 0.05). Serum T3 concentrations markedly decreased (1.07 +/- 0.07 vs 0.65 +/- 0.04 nmol/l), accompanied by a decrease of free T3 concentrations (p < 0.001). Serum rT3 concentrations increased by 50% (p < 0.001). Serum thyrotropin levels were mostly unmeasurable. The plasma clearance rate decreased slightly for T4 (19%, p < 0.05) and remarkably for rT3 (46.7%, p < 0.001). The conversion rate of T4 to rT3 did not change. Deiodinase type I (5'D-I) activity decreased in both liver and kidney tissues by 54% and 52%, respectively, and correlated with T3 (r2 = 0.79 and 0.65, respectively). Brain deiodinase type III (5D-III) was unchanged and type II (5'D-II) was unmeasurable.(ABSTRACT TRUNCATED AT 250 WORDS)