Oxidative DNA damage: the thyroid hormone-mediated effects of insulin on liver tissue

Abstract

Thyroid hormone affects glucose homeostasis with its actions between the skeletal muscle and liver and the altered oxidative and non-oxidative glucose metabolism. In our study three chemicals are considered biomarkers associated with oxidative stress for protein modifications were measured; 8-hydroxy-2-deoxyyguanosine (8-OHdG), a major lesion that can be generated by reactive oxygen species for DNA damage, protein carbonyl content (PCO), products of protein oxidation and advanced oxidation protein products (AOPPs) a dithyrosine containing cross-linked protein products. The purpose of the recent study was to determine the effects of insulin and T4 or their combination in diabetic, thyroidectomized, or diabetic-thyroidectomized rats and possible relations with oxidative DNA and protein damages. For this purpose, rats were assigned to eight groups: Group 1; control, Group 2; diabetes, Group 3; diabetes+insulin, Group 4; surgically thyroidectomized control, Group 5; thyroidectomized+diabetes, Group 6; thyroidectomized+diabetes+insulin, Group 7; thyroidectomized+diabetes+insulin+thyroid hormone, levothyroxin sodium, 2.5 μg/kg and Group 8; thyroidectomized+diabetes+insulin+thyroid hormone, levothyroxin sodium, 5.0 μg/kg for 5 weeks. After the genomic DNA of liver tissues was extracted, the ratio of 8-OHdG to deoxyguanosine and liver tissue protein oxidation markers was determined. The main findings of our recent study were the increased 8-OHdG levels during the diabetes, hypothyroidism, and hypothyroidism with diabetes, which can be regulated in different percentages with the treatment of 2.5 and 5.0 μg/kg doses of thyroid hormone and the altered protein carbonyl and AOPP levels of liver tissue. Consequently, it was observed that the DNA and protein damage induced by oxidative stress in diabetes could be regulated by dose-dependent thyroid hormone-mediated effects to insulin treatment.

Thyroid hormones-mediated effects of insulin on antioxidant enzymes from diabetic rat hearts

“…In another study with experimental diabetic rats, the decreased levels of thyroid hormones were maintained by insulin treatment (30). In our previous study, DNA damage could not be possibly controlled with insulin treatment but in surgically thyroidectomized rats with diabetes treated with both with insulin and appropriate thyroid hormone, the doses were succeeded (31). In our other studies (32), the stz-induced diabetic group data support this knowledge while showing a decrease in all serum thyroid hormone parameters in diabetes groups and an increase after insulin treatment.…”

Oxidative stress parameters in serum and low density lipoproteins of Hashimoto's thyroiditis patients with subclinical and overt hypothyroidism

“…Indeed, increased levels of serum protein oxidation were correlated with disease activity in some autoimmune diseases such as juvenile chronic arthritis [28], systemic lupus erythematosus [29] and rheumatoid arthritis [30]. PC levels were also reported to increase in experimental [34] and clinical hypothyroidism [13]. However, there is no study regarding serum PC levels in sHT and oHT patients.…”

Evaluation of inflammatory and oxidative biomarkers in children with well-controlled congenital hypothyroidism

“…DNA and protein damage induced by oxidative stress were observed in experimental hypothyroid animals (3,4) . Fortunately, the glomerular filtration rates between patients with CH and healthy children were not significantly different, although Brought to you by | New York University Bobst Library Technical Services Authenticated Download Date | 5/30/15 6:58 AM the mean values for fractional excretion of sodium and potassium were significantly higher in patients with CH (5) .…”

“…8-Hydroxydeoxyguanosine (8-OHdG), a major lesion marker that can be generated by DNA damage associated with reactive oxygen species, is the most commonly used biomarker of oxidative DNA damage. It can be induced by oxidative stress in diabetes and could thus be regulated dose dependently by thyroid hormone (4) . However, the effect of CH on urinary excretion of 8-OHdG is poorly understood.…”