In vitro free radical scavenging capacity of thyroid hormones and structural analogues

Abstract

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.

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

“…Thyroid hormones and structural analogues were reported to protect LDL from oxidation induced by non-cellular pro-oxidant agents (Hanna et al 1993, Chomard et al 1998, Oziol et al 2001 and by endothelial cells (Hanna et al 1995). In the present study, we found that these compounds also reduced macrophage-induced LDL oxidation in a concentration-dependent manner.…”

“…Transition metal ions like Fe 2+ may favour macrophage ROS generation and LDL radical attack (Xing et al 1998, Yuan & Brunk 1998. If the radical scavenging capacity of thyroid compounds was predominant outside the cells, T 3 and TA 3 ought to have decreased LDL lipid peroxidation more than T 4 and rT 3 , as previously found during AAPH-induced LDL oxidation (Oziol et al 2001); however, we found the contrary here. Since T 0 had no antioxidant effect here and considering the antioxidant capacity of Ham's F-10, as discussed above, it may be proposed that T 0 does not enter the macrophages whereas the other compounds do, and/or that these compounds act on macrophage cellular mechanisms whereas T 0 does not.…”

“…Furthermore, they also protected macrophages themselves from lipid peroxidation. Such an observation was foreseeable since analogues of thyroid hormones with a 4 -hydroxy diphenylether structure have free radical scavenging capacity (Oziol et al 2001) and since macrophages are able to generate ROS (Chisolm et al 1999, Kaplan & Aviram 1999) which may be captured by the thyroid compounds. The ability of thyroid compounds to decrease in vitro LDL oxidation induced by non-cellular prooxidant systems is a physico-chemical property of these compounds which may be effective whatever the prooxidant system.…”

“…The ability of thyroid compounds to decrease in vitro LDL oxidation induced by non-cellular prooxidant systems is a physico-chemical property of these compounds which may be effective whatever the prooxidant system. However, T 0 , which has a great antioxidant effect on Cu 2+ -or AAPH-induced LDL oxidation (Chomard et al 1998, Oziol et al 2001, was unable to protect LDL against macrophage-induced oxidation. This surprising observation led us to measure the antioxidant ability of the compounds in a classical in vitro LDL oxidation system, using Ham's F-10 medium as the working buffer.…”

“…Thyroid hormones and structural analogues have been shown to decrease the in vitro LDL oxidation induced by cuprous ions (Cu 2+ ) (Hanna et al 1993, Chomard et al 1998, the free radical generator 2,2 -azobis-[2-amidinopropane] dihydrochloride (AAPH) (Oziol et al 2001) or human endothelial cells (Hanna et al 1995). However, their effect on macrophage-induced LDL oxidation is unknown.…”