Hypothyroidism and the aorta. evidence of increased oxidative DNA damage to the aorta of hypothyroid rats.
BACKGROUND
Although it has been suggested that the hypometabolic state is associated with a decrease in oxidative stress, literature data are controversial, revealing an individuality of oxidant status in relation to tissue properties and responsiveness. Hypothyroidism has profound direct and indirect actions on the vascular system, inducing characteristic hemodynamic changes while the aorta represents an important determinant of vascular performance. This study aims to examine the oxidant status on the aorta in chronic experimental hypothyroidism.


METHODS
Chronic hypothyroidism was successfully induced in 20 male Wistar rats by administration of 0.05% 6-n-propyl 2-thiouracil in their drinking water for 8 weeks. Age-matched euthyroid rats were used as controls. Lipid peroxidation in the serum was determined by the end-product malondialdehyde (MDA). Oxidative damage to genomic DNA of aortic tissue and serum was investigated by measuring 8-oxo-dG, one of the base modifications produced in DNA by the reaction of reactive oxygen species. Serum lipids measurement was performed.


RESULTS
A hypothyroid state was confirmed by levels of serum thyroid hormones, lipidemic profile, clinical examination, pathological findings and cardiovascular hemodynamics parameters. Hypothyroidism was associated with a significant increase in lipid peroxidation. (MDA 1.44 +/-0.93 vs 0.64 +/- 0.53 nmol/l, p < 0 .01). Levels of 8-oxo-dG on the aortic ring, expressing the oxidant damage on genomic DNA and in the serum, were observed to be significantly raised in the hypothyroid group compared to controls (8-oxodG(serum) 29.22 +/- 17.78 vs. 17.56 +/- 4.44 ng/ml, p < 0.01; 8-oxo-dG(aorta)11.58 +/- 2.70 vs. 4.09 +/- 1.27 ng/ml, p < 0. 001). A statistical correlation between measurements of 8-oxo-dG in the aorta and serum was found (correlation coefficient = 0.36, p < 0.05). A hyperlipidemic profile in hypothyroid animals was revealed.


CONCLUSIONS
Vascular oxidative stress seems to play a pivotal role in the evolution of vascular pathology. Hypothyroidism was associated with increased DNA oxidative damage to the aorta. Hypercholesterolemia and an increase in mean arterial pressure associated with hypothyroidism may have a contributive role in the accumulation of damage in nuclear DNA of the vascular wall. 8-Oxo-dG is one of the mutagenic base modifications produced in DNA. Although clinical studies in other tissues have indicated a direct correlation between in vivo 8-oxo-dG formation and pathological processes, its role on the vascular wall needs further investigation.
Laboratory for Experimental Surgery and Surgical Research, School of Medicine, University of Athens, Greece. konmoulakakis@yahoo.gr
Konstantinos G
KG
Moulakakis
Maria V
MV
Poulakou
Theodosios
T
Dosios
Ismene
I
Dontas
Dimitrios P
DP
Sokolis
Ioannis S
IS
Vlachos
Michael C
MC
Safioleas
Antonios
A
Papachristodoulou
Panagiotis E
PE
Karayannacos
Despina N
DN
Perrea
D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D004249:DNA Damage; D007037:Hypothyroidism / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar