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.
Similar content being viewed by others
References
N. Bukan, B. Sancak, O. Yavuz, C. Koca, F. Tutkun, A.T. Ozcelikay, N. Altan, Lipid peroxidation and scavenging enzyme levels in the liver of streptozotocin-induced diabetic rats. Indian J. Biochem. Biophys. 40, 447–450 (2003)
N. Altan, C.O. Ongun, E. Hasanoğlu, A. Engin, C. Tuncer, S. Sindel, Effect of the sulfonylurea glyburide on superoxide dismutase activity in alloxan-induced diabetic rat hepatocytes. Diabetes Res. Clin. Pract. 22, 95–98 (1994)
T. Finkel, N.J. Holbrook, Oxidants, oxidative stress and the biology of aging. Nature 408, 239–247 (2000)
A. Valavanidis, T. Vlachogianni, C. Fiotakis, 8-hydroxy-2′-deoxyguanosine (8-OHdG): a critical biomarker of oxidative stress and carcinogenesis. J. Environ. Sci. Health. 27, 120–139 (2009)
M. Chevion, E. Berenshtein, E.R. Stadtman, Human studies related to protein oxidation: protein carbonyl content as a marker of damage. Free Radic. Res. 33, 99–108 (2000)
R.S. Sohal, S. Agarwal, A. Dubey, W.C. Orr, Protein oxidative damage is associated with life expectancy of houseflies. Proc. Natl. Acad. Sci. 90, 7255–7259 (1993)
C.J.J. Alderman, S. Shah, J.C. Foreman, B.M. Chain, D.R. Katz, The role of advanced oxidation protein products in regulation of dendritic cell function. Free Radic. Biol. Med. 32, 377–385 (2002)
V. Witko-Sarsat, M. Friedlander, C. Capeillere-Blandin, T. Nguyen-Khoa, A.T. Nguyen, J. Zingraff, P. Jungers, B. Descamps-Latscha, Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int. 49, 1304–1313 (1996)
O.H. Beenen, M. Pfaffendorf, P.A. Van Zwieten, Influence of the low thyroid state in diabetes mellitus on cardiac function and inotropic responsiveness to alpha 1-adrenoceptor stimulation: comparison with the role of hypothyroidism alone. J. Cardiovas. Pharamacol. 28, 553–557 (1996)
F. Kosova, A. Sepici-Dincel, A. Engin, L. Memiş, C. Koca, N. Altan, The thyroid hormone mediated effects of insulin on serum leptin levels of diabetic rats. Endocrine 33, 317–322 (2008)
M. Potenza, M.A. Via, R.T. Yanagisawa, Excess thyroid hormone and carbohydrate metabolism. Endocr. Pract. 15, 254–262 (2009)
P.K. Maiti, A. Kar, Is triiodothyronine capable of ameliorating pyrethroidinduced thyroid dysfunction and lipid peroxidation? J. Appl. Toxicol. 18, 125–128 (1998)
R.A. Floyd, J.J. Watson, P.K. Wong, D.H. Altmiller, R.C. Rickard, Hydroxyl free radical adduct of deoxyguanosine: sensitive detection and mechanisms of formation. Free Radic. Res. Commun. 1, 163–172 (1986)
B. Halliwell, M. Dizdaroglu, The measurement of oxidative damage to DNA by HPLC and GC/MS techniques. Free Radic. Res. Commun. 16, 75–87 (1992)
M.L. Hamilton, Z.M. Guo, C.D. Fuller, H. Van Remmen, W.F. Ward, S.N. Austad, D.A. Troyer, I. Thompson, A. Richardson, A reliable assessment of 8-oxo-2 deoxyguanosine levels in nuclear and mitochondrial DNA using the sodium iodide method to isolate DNA. Nucleic Acids Res. 29, 2117–2126 (2001)
R.L. Levine, J.A. Williams, E.R. Stadtman, E. Shacter, Carbonyl assays for determination of oxidatively modified proteins. Methods Enzymol. 233, 346–357 (1994)
M.S. Cooke, M.D. Evans, M. Dizdaroglu, J. Lunec, Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J. 17, 1195–1214 (2003)
M.D. Evans, M.S. Cooke, Factors contributing to the outcome of oxidative damage to nucleic acids. BioEssays 26, 533–542 (2004)
F. Erkoç, Ş. Erkoç, Structural and electronic properties of guanine and guanosine. J. Mol. Struct. (Theochem). 589–590, 405–411 (2002)
C.S. Shin, B.S. Moon, K.S. Park, S.Y. Kim, S.J. Park, M.H. Chung, H.K. Lee, Serum 8-hydroxy-guanine levels are increased in diabetic patients. Diabetes Care 24, 733–737 (2001)
J. Leinonen, T. Lehtimaki, S. Toyokuni, K. Okada, T. Tanaka, H. Hiai, H. Ochi, P. Laippala, V. Rantalaiho, O. Wirta, A. Pasternack, H. Alho, New biomarker evidence of oxidative DNA damage in patients with non-insulin-dependent diabetes mellitus. FEBS Lett. 417, 150–152 (1997)
S. Del Guerra, R. Lupi, L. Marselli, M. Masini, M. Bugliani, S. Sbrana, S. Torri, M. Pollera, U. Boggi, F. Mosca, S. Del Prato, P. Marchetti, Functional and molecular defects of pancreatic islets in human type 2 diabetes. Diabetes 54, 727–735 (2005)
R.H. Hsieh, L.M. Lien, S.H. Lin, C.W. Chen, H.J. Cheng, H.H. Cheng, Alleviation of oxidative damage in multiple tissues in rats with streptozotocin-induced diabetes by rice bran oil supplementation. Ann. N. Y. Acad. Sci. 1042, 365–371 (2005)
S.R. Kim, E.S. Tull, E.O. Talbott, M.T. Vogt, L.H. Kuller, A hypothesis of synergism: the interrelationship of T3 and insulin to disturbances in metabolic homeostasis. Med. Hypotheses 59, 660–666 (2002)
G. Andican, R. Gelisgen, S. Civelek, A. Seven, O. Seymen, T. Altug, G. Yigit, G. Burcak, Oxidative damage to nuclear DNA in hyperthyroid rat liver: inability of vitamin C to prevent the damage. J. Toxicol. Environ. Health A 67, 413–420 (2004)
M. Lopez-Torres, M. Romero, G. Barja, Effect of thyroid hormones on mitochondrial oxygen free radical production and DNA oxidative damage in the rat heart. Mol. Cell. Endocrinol. 168, 127–134 (2000)
C. Karasu, Y. Ozturk, N. Altan, N. Yildizoglu-Ari, C. Ikizler, V.M. Altan, Thyroid hormones mediated effect of insulin on alloxan diabetic rat atria. Gen. Pharmacol. 21, 735–740 (1990)
C.D. Rodgers, E.G. Noble, A.W. Taylor, The effect of STZ-induced diabetes on serum triiodothyronine (T3) and thyroxine (T4) levels in the rat: a seven week time course. Diabetes Res. 26, 93–100 (1994)
G. Alper, S. Irer, E. Duman, O. Caglayan, C. Yilmaz, Effect of I-deprenyl and gliclazide on oxidant stress/antioxidant status and DNA damage in a diabetic rat model. Endocr. Res. 31, 199–212 (2005)
T. Etoh, T. Inoguchi, M. Kakimoto, N. Sonoda, K. Kobayashi, J. Kuroda, H. Sumimoto, H. Nawata, Increased expression of NAD(P)H oxidase subunits, NOX4 and p22phox, in the kidney of streptozotocin-induced diabetic rats and its reversibity by interventive insulin treatment. Diabetologia 46, 1428–1437 (2003)
R. Pamplona, M. Portero-Otin, C. Ruiz, M.J. Bellmunt, J.R. Requena, S.R. Thorpe, J.W. Baynes, M. Romero, M. Lopez-Torres, G. Barja, Thyroid status modulates glycoxidative and lipoxidative modifications of tissue proteins. Free Radic. Biol. Med. 27, 901–910 (1999)
E.R. Stadtman, Protein oxidation and aging. Free Radic. Res. 40, 1250–1258 (2006)
R. Kayalı, U. Çakatay, Basic Mechanisms of Protein Oxidation (Protein Oksidasyonu Ana Mekanizmaları). Cerrahpaşa J. Med. 35, 83–89 (2004)
P. Gillery, Advanced glycation end products (AGEs), free radicals and diabetes. J. Soc. Biol. 195, 387–390 (2001)
R.T. Dean, S. Fu, R. Stocker, M.J. Davies, Biochemistry and pathology of radical mediated protein oxidation. Biochem. J. 324, 1–18 (1997)
U. Resch, G. Helsel, F. Tatzber, H. Sinzinger, Antioxidant status in thyroid dysfunction. Clin. Chem. Lab. Med. 40, 1132–1134 (2002)
U. Cakatay, Protein oxidation parameters in type 2 diabetic patients with good and poor glycaemic control. Diabetes Metab. 31, 551–557 (2005)
Acknowlegment
This study was supported by the Gazi University Project Foundation (BAP), Project No: 01-2006-07 and presented as poster in 20. National Biochemistry Congress, Kapadokya-Nevşehir, Türkiye, 29 October–1 November, 2008.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Altan, N., Sepici-Dinçel, A., Şahin, D. et al. Oxidative DNA damage: the thyroid hormone-mediated effects of insulin on liver tissue. Endocr 38, 214–220 (2010). https://doi.org/10.1007/s12020-010-9376-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12020-010-9376-7