Effect of levothyroxine administration on oxidative stress and cytokine levels in rats with experimental hypothyroidism

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Veröffentlicht: Απρ 11, 2023
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2023-04-11 (1)
DOI: https://doi.org/10.12681/jhvms.28743
ÇK Bozbek
M Şentürk
University of Erciyes, Faculty of Veterinary Medicine, Department of Biochemistry,Kayseri-TURKEY
https://orcid.org/0000-0002-3763-8310
Abstract

In this study, it was aimed to determine the effects of levothyroxine (L-T4) administration on serum free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH) and serum total antioxidant capacity (TAC), serum total oxidant capacity (TOC), oxidative stress index (OSI) and superoxide dismutase (SOD) activity, liver malondialdehyde (MDA) and the effects of cytokines on tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels in rats with experimental hypothyroidism. In the study, 48, 39-day-old, male Wistar albino rats were randomly divided into 3 groups containing 16 rats in each as control, hypothyroid and levothyroxine (L-T4) treated hypothyroid group. The rats in the control group were injected with 1 mL of saline and the rats in the hypothyroid group were injected via intraperitoneal (i.p.) route with 6-n-propyl thiouracil (PTU) at a dose of 10 mg/kg/day for 28 days. In the levothyroxine treated group, after induction of hypothyroidism 5 µg of levothyroxine diluted in 1 mL of sodium chloride (NaCl) administered via i.p. route for 15 days. At the end of the study, serum and liver samples were taken from the rats. In hypothyroidism group, serum fT3, fT4 and TAK levels as well as SOD (P<0.001) activity decreased statistically compared to the control group while serum TSH, TOC, OSI (P<0.001), liver MDA (P<0.01), TNF-α and IL-6 (P<0.001) levels increased significantly. The decreased serum fT3, fT4, TAC levels and SOD (P<0.001) activity in the hypothyroidism group increased with levothyroxine administration whereas the increased serum TSH, TOC, OSI and tissue MDA (P<0.01), TNF-α and IL-6 (P<0.001) levels were found to be decreased and approached to control levels. In conclusion, it has been shown that levothyroxine administration is effective against PTU-induced hypothyroidism in rats, inhibits lipid peroxidation and increases antioxidant status, minimizes the levels of inflammatory markers and protects against PTU-induced liver damage in rats. Because, the potential therapeutic use of levothyroxine in the treatment of hypothyroidism is thought to be appropriate.

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Autor/innen-Biografie
M Şentürk, University of Erciyes, Faculty of Veterinary Medicine, Department of Biochemistry,Kayseri-TURKEY

University of Erciyes, Faculty of Veterinary Medicine, Department of Biochemistry,
Kayseri-TURKEY

Literaturhinweise
Abdel-Wahhab KG, Mourad HH, Mannaa FA, Morsy FA, Hassan LK, Taher RF (2019) Role of ashwagandha methanolic extract in the regulation of thyroid profile in hypothyroidism modeled rats. Mol Biol Rep 46: 3637-3649.
Aksoy DY, Cinar N, Harmanci A, Karakaya J, Yildiz BO, Usman A, Bayraktar M (2013) Serum resistin and high sensitive CRP levels in patients with subclinical hypothyroidism before and after L-thyroxine therapy. Med Sci Monit 19: 210–215
Ates I, Altay M, Yilmaz FM, Topcuoglu C, Yilmaz N, Berker D, Guler S. (2016) The impact of levothyroxine sodium treatment on oxidative stress in Hashimoto's thyroiditis. Eur J Endocrinol 174: 727-34.
Aydın L, Mogulkoc R, Baltaci AK (2010) Influences of hypertonic and hypovolemic treatments on vasopressin response in propylthiouracil (PTU) induced hypothyroid rat and effect on supplementation with L-thyroxine. Acta Biol Hung 61: 1-9.
Baghcheghi Y, Salmani H, Beheshti F, Hosseini M (2017) Contribution of brain tissue oxidative damage in hypothyroidism-associated learning and memory impairments. Adv Biomed Res 6: 1-11.
Baser H, Can U, Baser S, Yerlikaya FH, Aslan U, Hidayetoglu BT (2014) Assesment of oxidative status and its association with thyroid autoantibodies in patients with euthyroid autoimmune thyroiditis. Endocrine 48: 916–923.
Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87: 245-313.
Beheshti F, Hosseini M, Shafei MN, Soukhtanloo M, Ghasemi S, Vafaee F, Zarepoor L (2017) The effects of Nigella sativa extract on hypothyroidism-associated learning and memory impairment during neonatal and juvenile growth in rats. Nutr Neurosci 20: 49-59.
Burek CL, Rose NR (2008) Autoimmune thyroiditis and ROS. Autoimmun Rev 7: 530-537.
Carmeli E, Bachar A, Barchad S, Morad M, Merrick J (2008) Antioxidant status in the serum of persons with intellectual disability and hypothyroidism: a pilot study. Res Dev Disabil 29: 431-438.
Chaalal A, Poirier R, Blum D, Gillet B, Le Blanc P, Basquin M, Buée L, Laroche S, Enderlin V (2014) PTU-induced hypothyroidism in rats leads to several early neuropathological signs of alzheimer's disease in the hippocampus and spatial memory impairments. Hippocampus 24: 1381-1393.
Costantini F, Pierdomenico SD, De Cesare D, De Remigis P, Bucciarelli T, Bittolo-Bon G, Cazzolato G, Nubile G, Guagnano MT, Sensi S, Cuccurullo F, Mezzetti A (1998) Effect of thyroid function on LDL oxidation. Arterioscler Thromb Vasc Biol 18: 732-737.
Dariyerli N, Toplan S, Akyolcu MC, Hatemi H, Yiğit G (2004) Erythrocyte osmotic fragility and oxidative stress in experimental hypothyroidism. Endocrine 25: 1-5.
Derhem B (2019) Birinci basamakta tiroiddisfonksiyonuna yaklaşım ve tarama. Anadolu Güncel Tıp Derg 1: 72-76.
Devadas S, Zaritskaya L, Rhee SG, Oberley L, Williams MS (2002) Discrete generation of superoxide and hydrogen peroxide by T cell receptor stimulation: selective regulation of mitogen-activated protein kinase activation and fas ligand expression. J Exp Med 195: 59-70.
Díez JJ, Hernanz A, Medina S, Bayón C, Iglesias P (2002) Serum concentrations of tumour necrosis factor-alpha (TNF-alpha) and soluble TNF-alpha receptor p55 in patients with hypothyroidism and hyperthyroidism before and after normalization of thyroid function. Clin Endocrinol (Oxf) 57: 515-521.
Dizdarevic-Bostandic A, Burekovic A, Velija-Asimi Z, Godinjak A (2013) Inflammatory markers in patients with hypothyroidism and diabetes mellitus type 1. Med Arch 67: 160-161.
Emerson CH (2018) Levothyroxine replacement for primary hypothyroidism can be given between meals with similar effectiveness at various times of the day. Clinical Thyroidology 30: 456-459.
Erdamar H, Demirci H, Yaman H, Erbil MK, Yakar T, Sancak B, Elbeg S, Biberoğlu G, Yetkin I (2008) The effect of hypothyroidism, hyperthyroidism, and their treatment on parameters of oxidative stress and antioxidant status. Clin Chem Lab Med 46: 1004-1010.
Faraji Shahrivar F, Badavi M, Dianat M, Mard A, Ahangarpour A, Samarbaf-Zadeh A (2016) Exogenous apelin changes alpha and beta myosin heavy chain mRNA expression and improves cardiac function in PTU-induced hypothyroid rats. Gene 595: 25-30.
Fernandez V, Llesuy S, Solari L, Kipreos K, Videla LA, Boveris A (1988) Chemiluminescent and respiratory responses related to thyroid hormone-induced liver oxidative stress. Free Radical Research Communications 5: 77–84.
Głombik K, Detka J, Budziszewska B (2021) Venlafaxine and L-Thyroxine treatment combination: ımpact on metabolic and synaptic plasticity changes in an animal model of coexisting depression and hypothyroidism. Cells 10: 1-22.
Güngör A, Bilen H, Akbaş EM, Özdemir Ç, Korkmaz L, Bulut N (2013) Levotiroksin sodyum intoksikasyonu: olgu sunumu. Abant Medical J 2: 227-228.
Hajje G, Saliba Y, Itani T, Moubarak M, Aftimos G, Fares N (2014) Hypothyroidism and its rapid correction alter cardiac remodeling. PLoS One 9: 1-11.
Haribabu A, Reddy VS, Pallavi Ch, Bitla AR, Sachan A, Pullaiah P, Suresh V, Rao PV, Suchitra MM (2013) Evaluation of protein oxidation and its association with lipid peroxidation and thyrotropin levels in overt and subclinical hypothyroidism. Endocrine 44: 152-157.
He L, He T, Farrar S, Ji L, Liu T, Ma X (2017) Antioxidants maintain cellular redox homeostasis by elimination of reactive oxygen species. Cell Physiol Biochem 44: 532-553.
Hosny EN, El-Gizawy MM, Sawie HG, Abdel-Wahhab KG, Khadrawy YA (2021) Neuroprotective effect of ashwagandha extract against the neurochemical changes induced in rat model of hypothyroidism. J Diet Suppl 18: 72-91.
https://www.ncbi.nlm.nih.gov/books/NBK551611/ [accessed 21 November 2021]
Jackson SH, Devadas S, Kwon J, Pinto LA, Williams MS (2004) T cells express a phagocyte-type NADPH oxidase that is activated after T cell receptor stimulation. Nat Immunol 5: 818-827.
Jena S, Chainy GB, Dandapat J (2012) Expression of antioxidant genes in renal cortex of PTU-induced hypothyroid rats: effect of vitamin E and curcumin. Mol Biol Rep 39: 1193-1203.
Kalyanaraman B (2013) Teaching the basics of redox biology to medical and graduate students: Oxidants, antioxidants and disease mechanisms. Redox Biol 1: 244-257.
Kılınç F, Aydın BB, Pekkolay Z, Çelik ME, Tuzcu AK (2015) Levotiroksinin toksikasyonu: olgu sunumu. Dicle Tıp Dergisi 42: 265-267.
Martinez B, del Hoyo P, Martin MA, Arenas J, Perez-Castillo A, Santos A (2001) Thyroid hormone regulates oxidative phosphorylation in the cerebral cortex and striatum of neonatal rats. J Neurochem 78: 1054-63.
McCord JM, Keele BB Jr, Fridovich I (1971) An enzyme-based theory of obligate anaerobiosis: the physiological function of superoxide dismutase. Proc Natl Acad Sci U S A 68: 1024-1027.
Monnereau A, Glaser SL, Schupp CW, Smedby KE, de Sanjosé S, Kane E, Melbye M, Forétova L, Maynadié M, Staines A, Becker N, Nieters A, Brennan P, Boffetta P, Cocco P, Glimelius I, Clavel J, Hjalgrim H, Chang ET (2013) Exposure to UV radiation and risk of Hodgkin lymphoma: a pooled analysis. Blood 122: 3492–3499.
Moriyama K, Tagami T, Usui T, Naruse M, Nambu T, Hataya Y, Kanamoto N, Li YS, Yasoda A, Arai H, Nakao K (2007) Antithyroid drugs inhibit thyroid hormone receptor-mediated transcription. J Clin Endocrinol Metab 92: 1066-1072.
Mullur R, Liu YY, Brent GA (2014) Thyroid hormone regulation of metabolism. Physiol Rev 94: 355-382.
Muthu PR, Bobby Z, Sankar P, Vickneshwaran V, Jacob SE (2018) Amla (Emblica officinalis) improves hepatic and renal oxidative stress and the inflammatory response in hypothyroid female wistar rats fed with a high-fat diet. J Basic Clin Physiol Pharmacol 29: 175-184.
Nakamura H, Noh JY, Itoh K, Fukata, S, Miyauchi A, Hamada N (2007) Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by graves' disease. J Clin Endocrinol Metab 92: 2157–2162.
Obradovic M, Gluvic Z, Sudar-Milovanovic E, Panic A, Trebaljevac J, Bajic V, Zarkovic M, Isenovic ER 2016) Nitric oxide as a marker for levo-thyroxine therapy in subclinical hypothyroid patients. Curr Vasc Pharmaco 14: 266-270.
Özyardımcı Ersoy C (2014) Hipotiroidizm tedavisi. Turkiye Klinikleri J Endocrin-Special Topics 7: 37-40.
Paital B (2018) Removing small non-enzymatic molecules for biochemical assay of redox regulatory enzymes; An exemplary comments on “Antioxidant responses in gills and digestive gland of oyster Crassostrea madrasensis (Preston) under lead exposure. Ecotoxicol Environ Saf 154: 337-340.
Pan T, Zhong M, Zhong X, Zhang Y, Zhu D (2013) Levothyroxine replacement therapy with vitamin E supplementation prevents oxidative stres and cognitive deficit in experimental hypothyroidism. Endocrine 43: 434–439.
Panda S, Kar A, Singh M, Singh RK, Ganeshpurkar A (2021) Syringic acid, a novel thyroid hormone receptor-β agonist, ameliorates propylthiouracil-induced thyroid toxicity in rats. J Biochem Mol Toxicol 35: 1-11.
Rizos CV, Elisaf MS, Liberopoulos EN (2011) Effects of thyroid dysfunction on lipid profile. Open Cardiovasc Med J 5: 76-84.
Rousset S, Alves-Guerra MC, Mozo J, Miroux B, Cassard-Doulcier AM, Bouillaud F, Ricquier D (2004) The biology of mitochondrial uncoupling proteins. Diabetes 1: 130-135.
Salama AF, Tousson E, Ibrahim W, Hussein WM (2013) Biochemical and histopathological studies of the PTU-induced hypothyroid rat kidney with reference to the ameliorating role of folic acid. Toxicol Ind Health 29: 600-608.
Salami M, Bandegi AR, Sameni HR, Vafaei AA, Pakdel A (2019) Hippocampal up-regulation of apolipoprotein D in a rat model of maternalhypo-and hyperthyroidism: implication of oxidativestress. Neurochemical Research 44: 2190–2201.
Şahin E, Bektur E, Baycu C, Burukoğlu Dönmez D, Kaygısız B (2019) Hypothyroidism increases expression of sterile inflammation proteins in rat heart tissue. Acta Endocrinol 5: 39-45.
Tahmaz L, Gökalp A, Kibar Y, Koçak I, Yalçin O, Özercan Y (2000) Effect of hypothyroidism on the testes in mature rats and treatment with levothyroxine and zinc. Andrologia 32: 85–89.
Torun AN, Kulaksizoglu S, Kulaksizoglu M, Pamuk BO, Isbilen E, Tutuncu NB (2009) Serum total antioxidant status and lipid peroxidation marker malondialdehyde levels in overt and subclinical hypothyroidism. Clin Endocrinol (Oxf) 70: 469-474.
Tuzcu A, Bahceci M, Gokalp D, Tuzun Y, Gunes K (2005) Subclinical hypothyroidism may be associated with elevated high-sensitive c-reactive protein (low grade inflammation) and fasting hyperinsulinemia. Endocr J 52: 89-94.
Venditti P, Di Meo S (2006) Thyroid hormone-induced oxidative stress. Cell Mol Life Sci 63: 414-434.
Wu CY, Liu B, Wang HL, Ruan DY (2011) Levothyroxine rescues the lead-induced hypothyroidism and impairment of long-term potentiation in hippocampal CA1 region of the developmental rats. Toxicol Appl Pharmacol 256: 191-197.
Ye J, Zhong X, Du Y, Cai C, Pan T (2017) Role of levothyroxine and vitamin E supplementation in the treatment of oxidative stress-induced injury and apoptosis of myocardial cells in hypothyroid rats. J Endocrinol Invest 40: 713-719.
Zhou J, Cheng G, Pang H, Liu Q, Liu Y (2018) The effect of 131I-induced hypothyroidism on the levels of nitricoxide (NO), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), total nitric oxide synthase (NOS) activity, and expression of NOS isoforms in rats, Bosn J Basic Med Sci 18: 305-312.