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)
Liang
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Department of Medicine, University of Geneva, Switzerland.
Morin
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O
Burger
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D000199:Actins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000633:toxicity*; D015152:Blotting, Northern; D007037:Hypothyroidism / Q000201:enzymology; D007453:Iodide Peroxidase / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009687:Nuclear Proteins; D011092:Polyethylene Glycols / Q000633:toxicity*; D011506:Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013961:Thyroid Gland / Q000187:drug effects*; D013963:Thyroid Hormones / Q000097:blood / Q000378:metabolism*; D013972:Thyrotropin / Q000097:blood / Q000378:metabolism; D013974:Thyroxine / Q000097:blood / Q000378:metabolism; D014018:Tissue Distribution / Q000187:drug effects; D014157:Transcription Factors; D014284:Triiodothyronine / Q000097:blood / Q000378:metabolism; D014285:Triiodothyronine, Reverse / Q000097:blood / Q000378:metabolism
D000199:Actins; D000975:Antioxidants; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; C051065:THRSP protein, human; C501478:Thrsp protein, rat; D013963:Thyroid Hormones; D014157:Transcription Factors; D014284:Triiodothyronine; C066840:TK 12627; D011092:Polyethylene Glycols; D014285:Triiodothyronine, Reverse; D013972:Thyrotropin; D007453:Iodide Peroxidase; D013974:Thyroxine