Influence of dietary iodine on drug-induced hypothyrodism in the rat.
Several compounds of pharmaceutical importance from a variety of chemical families, for example chlorpromazine and clomipramine, have been found to form charge-transfer complexes with iodine. We have investigated the influence of dietary iodine on thyroid-gland dysfunction induced by clomipramine, chlorpromazine or 2-thiazoline-2-thiol. We suggest that iodine is partly diverted from its metabolic pathway by complexation with drugs, and so the urinary concentration of iodide is increased. Both chlorpromazine and clomipramine, at doses which do not inhibit thyroperoxidase, enhanced urinary iodine excretion when dietary iodine was restricted (3.944+/-0.96 microg/day for chlorpromazine-tested rats, 3.43+/-1.33 microg/day for clomipramine-tested rats, compared with 2.34+/-0.11 microg/day in control rats). Concurrently, these pharmaceutical compounds increased the level of free thyroid-stimulating hormone (TSH) in comparison with controls and induced histological modifications in, and enlargement of, the thyroid gland. We have demonstrated that drug-induced loss of iodine in the urine was associated with antithyroid action when iodine intake was limited.
Beyssen
M L
ML
Department of Chemical Pharmacy, Faculty of Pharmacy, Limoges, France.
Lagorce
J F
JF
Cledat
D
D
Buxeraud
J
J
D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology*; D002746:Chlorpromazine / Q000494:pharmacology; D002997:Clomipramine / Q000494:pharmacology; D005260:Female; D007037:Hypothyroidism / Q000139:chemically induced*; D007455:Iodine / Q000008:administration & dosage* / Q000652:urine; D007784:Lactoperoxidase / Q000037:antagonists & inhibitors; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D013961:Thyroid Gland / Q000187:drug effects; D013972:Thyrotropin / Q000097:blood
D013956:Antithyroid Agents; D013844:Thiazoles; D053778:Thiazolidines; D013972:Thyrotropin; C005104:2-mercaptothiazoline; D007455:Iodine; D007784:Lactoperoxidase; D002997:Clomipramine; D002746:Chlorpromazine