Inhibition of in vitro macrophage-induced low density lipoprotein oxidation by thyroid compounds

Abstract

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 .

Ischemia-modified albumin levels in overt and subclinical hypothyroidism

“…However, the role of TSH in inducing inflammation has yet to be proved in vivo. In several studies, increased OS has been attributed to alterations in mitochondrial oxygen utilization [28], antiperoxidative nature of thyroid hormones [29], decreased clearance of oxidants, dyslipidemia, and excess TSH levels [1]. It was described that thyroid hormone biosynthesis is an oxidative biochemical reaction which depends on the formation of peroxides [30].…”

Serum total antioxidant status and lipid peroxidation marker malondialdehyde levels in overt and subclinical hypothyroidism

“…Thyroid hormones are the most important factors influencing the basal metabolic rate during normal physiological states by altering the mitochondrial oxygen consumption, the main production site of free radicals 2 . It is thus not surprising that changes in thyroid hormone levels affect the mitochondrial free‐radical generation, 2,3 as was previously shown in some animal models 4,5 . Thyroid hormones have been shown to affect the synthesis and degradation of the antioxidant proteins, vitamins and enzymes 6 .…”

“…Oxidative stress, which leads to oxidation of the main cellular macromolecules and a resultant molecular dysfunction, may result from either overproduction of free radicals or from insufficiency of several antioxidant defence systems 1 . Thyroid hormones are the most important factors influencing the basal metabolic rate during normal physiological states by altering the mitochondrial oxygen consumption, the main production site of free radicals 2 . It is thus not surprising that changes in thyroid hormone levels affect the mitochondrial free‐radical generation, 2,3 as was previously shown in some animal models 4,5 .…”

Serum Total Antioxidant Status, Lipid Profile, Malondialdehyde and Erythrocyte Superoxide Dismutase Levels in Hashimoto Thyroiditis Patients Treated with Levothyroxine

“…It is thus not surprising that changes in thyroid hormone levels affect the mitochondrial free radical generation, as was previously shown in some animal models. 9,10 Thyroid hormones have been shown to affect the synthesis and degradation of the antioxidant proteins, vitamins and enzymes. Because of an associated lower metabolic rate, hypothyroidism is expected to slow the free radical generation, as shown in several studies.…”