It was reported that thyroid hormones decreased Cu 2+ -induced low-density lipoprotein (LDL) oxidation in vitro. Here, we investigated free radical scavenging capacities of thyroid hormones (3,5,3 -tri-iodo-L-thyronine (T 3 ), thryoxine (T 4 ) and 3,3 ,5 -tri-iodo-L-thyronine (rT 3 )) and structural analogues (L-thryonine (T 0 ), 3,5,3 -tri-iodothyroacetic acid (TA 3 ) and 3,5,3 ,5 -tetraiodothyroacetic acid (TA 4 )), using three different models of free radical generation. T 0 , T 3 and TA 3 slowed down production of conjugated diene and thiobarbituric acidreactive substances during LDL oxidation by 2,2 -azobis-[2-amidinopropane] (water-soluble), whereas rT 3 , T 4 and TA 4 had practically no effect. In this system, T 0 was the more active compound. Using a 1,1-diphenyl-2-picrylhydrazyl (lipid-soluble) test, all compounds also revealed free radical scavenging capacities, but rT 3 , T 4 and TA 4 were more active than T 0 , T 3 and TA 3 . T 3 was able to scavenge superoxide anion and hydroxyl radicals generated in an aqueous phase by a xanthine-xanthine oxidase system, as measured by electron paramagnetic resonance spectroscopy. It may be concluded that: (1) thyroid hormones and analogues with a 4 -hydroxy diphenylether structure have free radical scavenging capacities, (2) this property is influenced by the number of iodines on the phenolic ring, and (3) thyroid hormone scavenging capacity should not be the only mechanism explaining their protective effect on Cu 2+ -induced LDL oxidation. The physiological significance of the findings is discussed.

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Oxidized low density lipoproteins (LDL) are highly suspected of initiating the atherosclerosis process. Thyroid hormones and structural analogues have been reported to protect LDL from lipid peroxidation induced by Cu 2+ or the free radical generator 2,2 -azobis-[2-amidinopropane] dihydrochloride in vitro. We have examined the effects of thyroid compounds on macrophage-induced LDL oxidation. Human monocyte-derived macrophages (differentiated U937 cells) were incubated for 24 h with LDL and different concentrations (0-20 µM) of 3,5,3 -triiodo--thyronine (T 3 ), 3,5,3 ,5 -tetraiodo-L-thyronine (T 4 ), 3,3 ,5 -tri-iodo--thyronine (rT 3 ), the T 3 acetic derivative (3,5,3 -tri-iodothyroacetic acid; TA 3 ) or L-thyronine (T 0 ) (experiment 1). Cells were also preincubated for 24 h with 1 or 10 µM of the compounds, washed twice, then incubated again for 24 h with LDL (experiment 2). Oxidation was evaluated by measurement of thiobarbituric acid-reactive substances (TBARS) and cell viability by lactate deshydrogenase release. In experiment 1, T 0 had no effect, whereas the other compounds decreased LDL TBARS production, but T 3 and TA 3 were less active than T 4 and rT 3 (IC 50 : 11·0 2·6 and 8·1 0·8 vs 1·4 0·5 and 0·9 0·3 µM respectively). In experiment 2, the compounds at 1 µM had no effect; at 10 µM, T 3 and rT 3 slightly reduced LDL TBARS production, whereas TA 3 and T 4 inhibited it by about 50% and 70% respectively. TBARS released by the cells were also highly decreased by T 3 , T 4 , rT 3 and TA 3 in experiment 1, but only by T 3 (30%) and T 4 (70%) in experiment 2. Cell viability was not affected by the compounds except slightly by TA 3 at 10 µM. The data suggested that the physicochemical antioxidant capacity of thyroid compounds was modulated by their action on the intracellular redox systems of macrophage. Overall cellular effects of T 3 led to a reduction of its antioxidant capacity whereas those of T 4 increased it. Thus T 4 might protect LDL against cellular oxidation in vivo more than T 3 .

Male Wistar rats, 3 weeks old, were thyroidectomized surgically, kept for 1 month at 25 degrees C and then fasted for 3 days, with or without daily intraperitoneal injection of 3,5,3'-triiodo-L-thyronine (4.6 nmol T3/100 g body weight). Age-matched fed euthyroid rats were used as controls. All the experiments were carried out using isolated epididymal adipocytes. Basal lipolysis was higher during fasting in euthyroid or T3-treated adipocytes than in hypothyroid adipocytes. Adipocytes of fed hypothyroid rats were quite unresponsive to theophylline alone or combined with adrenaline or isoproterenol, whereas lipolysis was stimulated by these drugs in euthyroid or T3-treated adipocytes. Such a stimulated lipolysis was increased partially by fasting in hypothyroid adipocytes and was restored to a euthyroid level in T3-treated adipocytes. Lipolysis was more stimulated by adenosine deaminase in fasted euthyroid adipocytes than in fed ones. Hypothyroid and T3-treated adipocytes were unresponsive to adenosine deaminase except in fasted T3-treated rats. In these adipocytes, lipolysis was activated by the combination of adenosine deaminase plus theophylline. Finally, lipolysis was inhibited strongly in hypothyroidism while it was activated weakly by fasting. Lipolysis was inhibited slightly in fasted hypothyroid rats and thyroid hormone restored lipolysis. The findings are discussed in terms of the dual regulation of lipolysis by fasting and thyroid hormones.

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