Oxidative DNA damage: the thyroid hormone-mediated effects of insulin on liver tissue.
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.
Altan
Nilgün
N
Department of Medical Biochemistry, Faculty of Medicine, Gazi University, Ankara, Turkey. naltan@gazi.edu.tr
Sepici-Dinçel
Aylin
A
Sahin
Duygu
D
Kocamanoğlu
Nilgün
N
Kosova
Funda
F
Engin
Atilla
A
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013965:Thyroidectomy; D013974:Thyroxine / Q000378:metabolism / Q000494:pharmacology*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D013974:Thyroxine