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
Abstract:
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 ratsSource:
University of Belgrade, Faculty of Biology, 2017, 1-150Funding / projects:
- The effects of select plant extracts, phytoestrogens, steroid and peptide hormones on the rat neuroendocrine system (RS-MESTD-Basic Research (BR or ON)-173009)
URI
http://uvidok.rcub.bg.ac.rs/handle/123456789/2210https://radar.ibiss.bg.ac.rs/handle/123456789/2881