Uticaj citrusnih flavanona na tiroidnu homeostazu i lipidni status starih pacova
Impact of citrus flavanones on thyroid homeostasis and lipid status of old-aged rats
Doctoral thesis (Published version)
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Citrus flavanones, naringenin (NAR) and hesperetin (HES), are polyphenolic substances, structurally similar to endogenous thyroxine (T4), that can interfere with the activity of thyroid peroxidase, the key enzyme in thyroid hormone biosynthesis. With aging, thyroid axis sensitivity to the effects of exogenously applied substances increases and the risk of chronic diseases raises due to reduced detoxification ability and the accumulation of lipids in the liver. The aim of this doctoral dissertation was to examine the impact of NAR and HES on thyroid homeostasis and the lipid status of 24 monthsold Wistar male rats. The substances were administered per os at a dose of 15 mg/kg b.w., for four weeks. The results of this dissertation have shown that NAR and HES cause structural and ultrastructural changes in the thyroid gland of old male rats, increasing the immunohistochemical expression of T4 bounded to thyroglobulin as well as of vascular endothelial growth factor. Expression of triiodothyronine (T3) regulated genes in the liver were decreased after treatment with citrus flavanones. In the serum, the NAR increased concentrations of TSH and HDL, while the concentration of liver antioxidative enzymes was reduced after both treatments. The desaturation of fatty acids in the hepatocyte membrane phospholipids, the increase in the proportion of n-3, and the reduction in the presence of n-6 fatty acids after application of both citrus flavanones is observed. Lipid peroxidation of the hepatocyte membrane is reduced and the antioxidant protection is improved in the liver after NAR and HES treatments. The NAR has a stronger effect, as it has affected the activity, gene and protein expression of antioxidant enzymes, as well as the parameters of redox balance, while HES enhanced antioxidant protection, but to a less degree. The use of citrus flavanones causes unwanted effects - subclinical hypothyrosis followed by elevated TSH and reduced expression of T3 regulated genes in the liver. However, from the perspective of the hepatocyte membrane desaturation and the enhancement of antioxidant protection in the liver, the use of NAR and HES can be considered useful, given that the effects of these changes are associated with the extend life span.
Keywords:Citrus flavanones; Naringenin; Hesperetin; Thyroid gland; Thyroid homeostasis; Liver; Lipid status; Phospholipid fatty acid profile; Antioxidant defence; Oldaged Wistar rats
Source:University of Belgrade, Faculty of Biology, 2017, 1-150
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