ANTIGOITROGENIC EFFECT OF COMBINED SUPPLEMENTATION WITH DL-ALPHA-TOCOPHEROL, ASCORBIC-ACID AND BETA-CAROTENE AND OF DL-ALPHA-TOCOPHEROL ALONE IN THE RAT

The effects of the vitamins dl-alpha-tocopherol, ascorbic acid and bet a-carotene, free radical scavengers and lipid peroxidation inhibitors, were analyzed in male Wistar rats made goitrous by feeding a low iodi ne diet (<20 mu g iodine/kg) and perchlorate (1% in drinking water) fo r 4, 8, 16 and 32 days. Groups of control or goitrous rats received fo r at least 16 days before killing a diet containing 0.6% vitamin E (as dl-alpha-tocopherol acetate), 1.2% vitamin C (ascorbic acid) and 0.48 % beta-carotene, either simultaneously (vitamin cocktail) or separatel y. This treatment led to a 5-fold increase of vitamin E in the thyroid gland, a 24-fold increase in the liver and a 3-fold increase in the p lasma. In control rats, vitamin cocktail administration increased slig htly tile thyroid weight with little changes in thyroid function param eters. During iodine deficiency, administration of the vitamin cocktai l or vitamin E alone reduced significantly the rate of increase in thy roid weight, and DNA and protein contents, as well as the proportion o f [H-3]thymidine labeled thyroid follicular cells, but not that of lab eled endothelial cells. Plasma tri-iodothyronine, thyroxine, TSH level s, thyroid iodine content and concentration as well as relative volume s of glandular compartments were not modified. The proportion of necro tic cells rose from 0.5% in normal animals to about 2% after 16 days o f goiter development. No significant protective effect of the vitamins was observed. These results suggest that these vitamins, particularly vitamin E, modulate one of the regulatory cascades involved ill the c ontrol of thyroid follicular cell growth, without interfering with the proliferation of endothelial cells.