Effect of Thyroid Function on LDL Oxidation

Abstract

Abstract-In this study, the effect of different levels of thyroid hormone and metabolic activity on low density lipoprotein (LDL) oxidation was investigated. Thus, in 16 patients with hyperthyroidism, 16 with hypothyroidism, and 16 age-and sex-matched healthy normolipidemic control subjects, the native LDL content in lipid peroxides, vitamin E, ␤-carotene, and lycopene, as well as the susceptibility of these particles to undergo lipid peroxidation, was assessed. Hyperthyroidism was associated with significantly higher lipid peroxidation, as characterized by a higher native LDL content in lipid peroxides, a lower lag phase, and a higher oxidation rate than in the other two groups. This elevated lipid peroxidation was associated with a lower LDL antioxidant concentration. Interestingly, hypothyroid patients showed an intermediate behavior. In fact, in hypothyroidism, LDL oxidation was significantly lower than in hyperthyroidism but higher than in the control group. Hypothyroidism was also characterized by the highest ␤-carotene LDL content, whereas vitamin E was significantly lower than in control subjects. In hyperthyroidism but not in the other two groups, LDL oxidation was strongly influenced by free thyroxine blood content. In fact in this group, the native LDL lipid peroxide content and the lag phase were directly and indirectly, respectively, related to free thyroxine blood levels. On the contrary, in hypothyroidism LDL oxidation was strongly and significantly related to serum lipids. In conclusion, both hypothyroidism and hyperthyroidism are characterized by higher levels of LDL oxidation when compared with normolipidemic control subjects. In hyperthyroid patients, the increased lipid peroxidation was strictly related to free thyroxine levels, whereas in hypothyroidism it was strongly influenced by serum lipids. 1 Overt hyperthyroidism and hypothyroidism represent opposite clinical conditions characterized respectively by enhanced oxidative metabolism and reduced lipid and lipoprotein plasma levels and by reduced oxidative metabolism and markedly increased lipid and lipoprotein plasma levels. The hypermetabolic state that characterizes hyperthyroidism should accelerate free radical production in the mitochondria and induce changes in the antioxidant defense system. 2,3 In contrast, the metabolic suppression brought about by hypothyroidism is associated with a decrease in free radical production, and it has also been suggested that hypothyroidism protects tissues against acceleration of lipid peroxidation. [3][4][5] Increasing experimental and epidemiological evidence shows that high oxidative stress status favors oxidative modifications of LDL and plays an important role in the development of atherosclerosis.6-8 Nevertheless, hypothyroidism but not hyperthyroidism represents an important risk factor for atherosclerosis and coronary heart disease. 9 In view of well-documented strong relationships between blood cholesterol, LDL oxidation, and atherosclerosis, we used two opposite metabolic conditions, overt...

Baseline Levels and Trimestral Variation of Triiodothyronine and Thyroxine and Their Association with Mortality in Maintenance Hemodialysis Patients

“…Although adjustment for s-albumin (one of the main transporters of T3 in plasma) did not modify the observed associations, we should acknowledge that fT3 is not tantamount to T3. Several studies have, nevertheless, suggested anti-atherosclerotic effects of fT3 on the vascular bed via its effect on mitochondrial oxidative systems, induction of vasodilatory molecules, inhibition of angiotensin II receptor expression and inhibition of downstream signal transduction, mechanisms all of which do not necessarily involve the inflammatory cascade (26)(27)(28).…”

Influence of hypothyroidism on lipid peroxidation, erythrocyte resistance and antioxidant plasma properties in rabbits

“…The organic chain-breaking antioxidant potential of plasma appeared to be rather low and decreased in hypothyroidism. Such conditions may be in part caused by the low plasma primary chain-breaking antioxidant -α-tocopherol -content observed concomitantly with hypothyroid state (Constantini et al, 1998;Shinohara et al, 2000). Although the blood plasma of euthyroid rabbits possesses very high inorganic iron-binding, iron-oxidising and scavenging activities (from 77.1% to 86.9% of oxygen radicals inhibition), no alteration in these activities were noticed in hypothyroid rabbits.…”

“…Pamplona et al (1999) suggest that thyroid hormones acting as physiologic modulators of tissue oxidative stress and protein degradation are more effective in cytosol, whereas DNA is more protected from oxidative damage. In humans, the low density lipoprotein (LDH) oxidation was shown to be significantly lower in hypothyroid than in hyperthyroid subjects (Constantini et al, 1998).…”

Spectrum of Lipid Abnormality among Thyroid Disorder Patients in Ucms-Th, South Western Region

“…6,7,8 dyslipidemia But in patients with overt hypothyroidism, activity of HMG-CoA reductase tends to decrease while TC 9,10 and LDL-C levels are increased. This can be explained as increased thyroid hormones leads to decresedcatabolism of 11,12 LDL and IDL Hyperthyroidism canalso be the contributory factor that may cause unexpected improvement of lipid profile 13 in hyperlipidemic patients Since, hyperthyroidism whether overt or subclinical , there is decrease in LDLand HDL cholesterol resulting enhanced oxidation of LDL that depends 14 on level of FT4. Decrease in HDL-C levels is associated with increased CETP-mediated transfer of cholesteryl esters from HDL to VLDL and increased HL-mediated catabolism of 15,16 HDL .…”