Hyperthyroidism is Associated with Increased Aortic Oxidative DNA Damage in a Rat Model

Abstract

Background: Hyperthyroidism is associated with increased oxidative stress and oxygen free radical production. Oxygen free radicals are implicated in several signalling pathways leading to vascular pathology. The present study evaluates the extent of aortic oxidative stress in experimental hyperthyroidism. Materials and Methods: Chronic hyperthyroidism was induced in 20 male Wistar rats; another 20 animals served as controls. Oxidative damage to lipids and genomic DNA was assessed by measuring serum and aortic wall 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) levels (a mutagenic marker of oxidative DNA damage), as well as serum ceruloplasmin, malondialdehyde (MDA) and lipids. Results: Hyperthyroid animals had significantly higher values of serum ceruloplasmin (11.27±1.16 vs. 9.58±1.17 mg/dl), MDA (5.34±1.32 vs. 0.64±0.53 nmol/ml) and 8-oxo-dG (33.91±9.63 vs. 17.56±4.44 ng/ml) compared with controls (p<0.001 for all associations). Aortic 8-oxo-dG levels were elevated in the thyrotoxic compared with the control group (13.01±2.38 vs. 4.09±1.27 ng/ml, respectively; p<0.001). 8-Oxo-dG measurements in aortic rings and in serum were positively correlated in the hyperthyroid rats (Pearson's correlation coefficient=0.66; p=0.007). Conclusion: Hyperthyroidism is associated with increased oxidative stress in the aortic wall. The animal model we describe has provided some preliminary data regarding the effect of hyperthyroidism on the vascular system. Verification of our results and further exploration of our animal model may help determine the association between oxidative DNA damage with functional changes of the vascular wall, such as endothelial function and vascular nitric oxide signalling.