Influence of hyperthyroidism on hepatic antioxidants and cytokines Levels: An Experimental Study
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Objective: Thyroid diseases greatly affect the liver. Hyperthyroidism can affect the function of the liver. This study aimed to investigate the possible change of antioxidant and pro-inflammatory cytokines levels in liver tissue in hyperthyroid rats.
Material and Methods: This study was carried out with 2 experimental groups. Hyperthyroid group was fed with 4 mg/kg L-thyroxine added standard fodder. Control group was fed with standard rat fodder. Liver selenium (Se) levels were measured by inductively coupled plasma optical emission spectrophotometer (ICP-OES). The antioxidant markers such as Selenoprotein P (SelP), and glutathione peroxidase (GPx), and the pro-inflammatory cytokines such as Interleukin (IL)-18, and Tumor necrosis factor-α (TNF-α) levels were studied in liver tissues by ELISA. All markers levels of liver samples were measured in tissue homogenates.
Results: Se, SelP, and GPx levels of the hyperthyroidism group were lower than the control group. (p=0.038, p=0.046, p=0.008 respectively). There was a significant increase in IL-18 and TNF-α levels in hyperthyroidism group when compared to control group (p=0.002, p=0.023 respectively). There was positive correlation between FT3 and FT4, IL-18 and TNF-α (r=0.761, r=0.843, and r=0.826 respectively), but there was negative correlation between FT3 and Se, SelP, and GPx (r=-0.833, r=-0.754, and r=-0.778 respectively).
Conclusion: Our findings showed that antioxidant marker levels were decreased, and pro-inflammatory cytokine levels were increased in liver tissues of hyperthyroid rats. These findings suggest that impaired antioxidant and pro-inflammatory status may play a role in liver pathogenesis due to hyperthyroidism.
Gomaa AM, Abd El-Aziz EA. Omega-3 fatty acids decreases oxidative stress, tumor necrosis factor-alpha, and interleukin-1 beta in hyperthyroidism-induced hepatic dysfunction rat model. Pathophysiology. 2016;23(4):295-301.
Hazzaa S, Badr E, Abdou A. The Link Between Oxidative Stress Response and Tumor Necrosis Factor-Alpha (TNF-alpha) in Hepatic Tissue of Rats With Induced Thyroid Dysfunction. J. Afr. Ass. Physiol. Sci. 2013; 1 (1): 47 – 54.
Assaei R, Zal F, Mostafavi-Pour Z, Dabbaghmanesh MH, et al. Hepatoprotective effect of satureja khuzestanica essential oil and vitamin e in experimental hyperthyroid rats: evidence for role of antioxidant effect. Iran J Med Sci. 2014;39(5):459-66.
Gianoukakis AG, Khadavi N, Smith TJ. Cytokines, Graves' disease, and thyroid-associated ophthalmopathy. Thyroid. 2008; 18(9):953-8.
Rozing MP, Westendorp RG, Maier AB, Wijsman CA, Frölich M, de Craen AJ, van Heemst D. Serum triiodothyronine levels and inflammatory cytokine production capacity. Age (Dordr). 2012;34(1):195-201.
Fernández V, Tapia G, Varela P, Romanque P, Cartier-Ugarte D, Videla LA Thyroid hormone-induced oxidative stress in rodents and humans: a comparative view and relation to redox regulation of gene expression. Comp Biochem Physiol C Toxicol Pharmacol. 2006 Mar-Apr;142(3-4):231-9.
Messarah M, Boumendjel A, Chouabia A, et al. Influence of thyroid dysfunction on liver lipid peroxidation and antioxidant status in experimental rats. Experimental and Toxicologic Pathology. 2010;62(3):301–310.
Lin TY, Shekar AO, Li N, Yeh MW, Saab S, Wilson M, Leung AM. Incidence of abnormal liver biochemical tests in hyperthyroidism. Clin Endocrinol (Oxf). 2017;86(5):755-759.
Özdemir S, Yücel R, Dariyerli N et al. The effects of experimental hyperthyroidism on hemorheology and plasma fibrinogen concentration. Endocrine 2006; 30: 203-205.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193(1):265-75.
Chi HC, Tsai CY, Tsai MM, Yeh CT, Lin KH. Molecular functions and clinical impact of thyroid hormone-triggered autophagy in liver-related diseases. J Biomed Sci. 2019 Mar 8;26(1):24.
Tapia G, Fernández V, Varela P, Cornejo P, Guerrero J, Videla LA. Thyroid hormone-induced oxidative stress triggers nuclear factor-kappaB activation and cytokine gene expression in rat liver. Free Radic Biol Med. 2003;35(3):257-65.
Meligy FY, Ola A. Hussein OA, Mubarak HAE, Abdel MM. The possible protective role of omega 3 on liver of L thyroxine treated male albino rats. Histological and immunhistochemical study. Journal of Medical Histology. 2018; 8(2):131-144.
Subudhi U and Chainy GB. Expression of hepatic antioxidant genes in l-thyroxine-induced hyperthyroid rats: regulation by vitamin E and curcumin. Chem Biol Interact 2010; 183: 304-
Subudhi U, Das K, Paital B, Bhanja S and Chainy GB. Alleviation of enhanced oxidative stress and oxygen consumption of L-thyroxine induced hyperthyroid rat liver mitochondria by vitamin E and curcumin. Chem Biol Interact. 2008; 173: 105-114.
Luo H, Li X, Xiao S, Zhang X. Effect of Shenmaisanjie capsules on hyperthyroidism-induced liver damage in rat. Int J Clin Exp Med. 2017;10(8):11903-11911.
Venditti P, De Rosa R, Di Meo S. Effect of thyroid state on H2O2 production by rat liver mitochondria. Mol Cell Endocrinol. 2003;205:185-92.
Ferna´ndez V, Cornejo P, Tapia G and Videla L. Influence of hyperthyroidism on the activity of liver nitric oxide synthase in the rat. Nitric Oxide. 1997;1(6):463-468.
Boisier X, Schön M, Sepúlveda A, Basualdo A, et al. Derangement of Kupffer cell functioning and hepatotoxicity in hyperthyroid rats subjected to acute iron overload. Redox Rep. 1999;4(5):243-50.
Venditti P, Balestrieri M, Di Meo S, De Leo T. Effect of thyroid state on lipid peroxidation, antioxidant defences, and susceptibility to oxidative stress in rat tissues. J. Endocrinol.1997; 155: 151–157.
Asayama K, Dobashi K, Hayashibe, Megata Y, Kato K. Lipid peroxidation and free radical scavengers in thyroid dysfunction in the rat: a possible mechanism of injury to heart and skeletal muscle in hyperthyroidism. Endocrinology. 1987; 121: 2112-2118.
Malik R, Hodgson H. The relationship between the thyroid gland and the liver. Q J Med. 2002; 95:559–569.
Mehdi Y, Hornick JL, Istasse L, Dufrasne I. Selenium in the environment, metabolism and involvement in body functions. Molecules. 2013;18(3):3292-3311.
Mostert V. Selenoprotein P: Properties, functions, and regulation. Arch. Biochem. Biophys. 2000;376, 433–438.
Mannaa FA, Abdel-Wahhab KG. Physiological potential of cytokines and liver damages. Hepatoma Res. 2016;2:131-43.
Sekiyama KD, Yoshiba M, Thomson AW. Circulating proinflammatory cytokines (IL-1 beta, TNF-alpha, and IL-6) and IL-1 receptor antagonist (IL-1Ra) in fulminant hepatic failure and acute hepatitis. Clin Exp Immunol. 1994; 98(1): 71–77.
Prystupa A, Kiciński P, Sak J et al. Proinflammatory Cytokines (IL-1α, IL-6) and Hepatocyte Growth Factor in Patients with Alcoholic Liver Cirrhosis. Gastroenterol Res Pract. 2015; 2015: 532615.
Finotto S, Siebler J, Hausding M, Schipp M, Wirtz S et al. Severe hepatic injury in interleukin 18 (IL-18) transgenic mice: a key role for IL-18 in regulating hepatocyte apoptosis in vivo. Gut. 2004;53(3):392-400.
Wheelhouse NM, Chan1 Y-S, Gillies SE, Caldwell H, et al. TNF-a induced DNA damage in primary murine hepatocytes. International Journal of Molecular Medicine. 2003;12: 889-894.