Original Article

Effects of Levothyroxine and Liothyronine on Cirrhotic Cardiomyopathy in Rats

Abstract

In liver cirrhosis, there is low T3 syndrome associated with a decrease in total triiodothyronine (T3) and free T3 concentrations and cirrhotic cardiomyopathy (CCM) with chronotropic incompetence. Thus, we aimed to investigate the effects of eliminating T3 and thyroxine (T4) deficiencies on cardiac chronotropic dysfunction. Bile duct ligation (BDL) was used to induce cirrhosis in male Wistar rats. The chronotropic responses were studied through the Power Lab system in sham/saline, sham/T3T4, BDL/saline, and BDL/T3T4 groups. The serum T3 and T4, and T3 resin uptake (T3RU) levels were assessed. The atrial T3 receptor expression was investigated through a real-time polymerase chain reaction (Real-time PCR). The chronotropic responses were decreased in the BDL/saline group and raised in the BDL/T3T4 group. The serum T3 levels decreased in the BDL/saline group compared to sham group, but increased in the BDL/T3T4 group compared to the BDL/saline group. The serum T4 level increased in the BDL/saline and decreased in the BDL/T3T4 group. The serum T3RU level decreased in the BDL/saline and increased in the BDL/T3T4 group. The T3 receptor expression in atria increased in the BDL/saline group, nonetheless, it did not change in the BDL/T3T4 group compared to the sham/saline and the BDL/saline groups. T3T4 treatment did not increase the chronotropic response in the control group but the treatment improved the chronotropic hyporesponsiveness, and serum T4 and T3 RU abnormalities in cirrhosis, however, it is not related to the atrial T3 receptor expression.

1. Iwakiri Y. Endothelial dysfunction in the regulation of cirrhosis and portal hypertension. Liver international. 2012;32(2):199-213.
2. Moezi L, Dehpour AR. Cardiovascular abnormalities in obstructive cholestasis: the possible mechanisms. Liver International. 2013;33(1):7-15.
3. Vallance P, Moncada S. Hyperdynamic circulation in cirrhosis: a role for nitric oxide? The Lancet. 1991;337(8744):776-8.
4. Xia J-L, Dai C, Michalopoulos GK, Liu Y. Hepatocyte growth factor attenuates liver fibrosis induced by bile duct ligation. The American journal of pathology. 2006;168(5):1500-12.
5. Schuppan D, Afdhal NH. Liver cirrhosis. The Lancet. 2008;371(9615):838-51.
6. Chayanupatkul M, Liangpunsakul S. Cirrhotic cardiomyopathy: review of pathophysiology and treatment. Hepatology international. 2014;8(3):308-15.
7. Dan G-A. Thyroid hormones and the heart. Heart failure reviews. 2016;21(4):357-9.
8. Punekar P, Sharma AK, Jain A. A study of thyroid dysfunction in cirrhosis of liver and correlation with severity of liver disease. Indian journal of endocrinology and metabolism. 2018;22(5):645.
9. Verma SK, Kumar V, Tiwari P, Joge NKP, Misra R. Thyroid Profile in Patients of Cirrhosis of Liver: A Crosssectional Study. Journal of Clinical & Diagnostic Research. 2017;11(12).
10. Agiasotelli D, Alexopoulou A, Vasilieva L, Dourakis SP. Low free T3 levels are related to early mortality in patients with decompensated cirrhosis and acute-on chronic liver failure. Journal of hepatology. 2014;61(6):1446-7.
11. Levey GS. Catecholamine sensitivity, thyroid hormone and the heart: a reevaluation. Elsevier; 1971.
12. Vargas-Uricoechea H, Bonelo-Perdomo A, Sierra-Torres CH. Effects of thyroid hormones on the heart. Clínica e Investigación en Arteriosclerosis. 2014;26(6):296-309.
13. Doustimotlagh AH, Dehpour AR, Etemad-Moghadam S, Alaeddini M, Kheirandish Y, Golestani A. Nitrergic and opioidergic systems affect radiographic density and histomorphometric indices in bile-duct-ligated cirrhotic rats. Histol Histopathol. 2017;32(7):743-9.
14. Ortiz VD, De Castro AL, Campos C, Fernandes RO, Bonetto JH, Siqueira R, et al. Effects of thyroid hormones on aortic tissue after myocardial infarction in rats. European Journal of Pharmacology. 2016;791:788-93.
15. Mani AR, Ippolito S, Ollosson R, Moore KP. Nitration of cardiac proteins is associated with abnormal cardiac chronotropic responses in rats with biliary cirrhosis. Hepatology. 2006;43(4):847-56.
16. Auer J, Berent R, Weber T, Lassnig E, Eber B. Thyroid function is associated with presence and severity of coronary atherosclerosis. Clinical Cardiology: An International Indexed and Peer‐Reviewed Journal for Advances in the Treatment of Cardiovascular Disease. 2003;26(12):569-73.
17. Kim M, Lee B-C. Therapeutic Effect of Scutellaria baicalensis on L-Thyroxine-Induced Hyperthyroidism Rats. Evidence-Based Complementary and Alternative Medicine. 2019;2019.
18. Auth Jr JC. Effects of exercise upon circulating thyroxine serum and hepatic lipid concentrations, heart, and seminal vesicles in rats and of age and exercise upon circulating thyroxine in humans. 1976.
19. Fazio S, Palmieri EA, Lombardi G, Biondi B. Effects of thyroid hormone on the cardiovascular system. Recent progress in hormone research. 2004;59(1):31-50.
20. Møller S, Henriksen JH. Cirrhotic cardiomyopathy. Journal of hepatology. 2010;53(1):179-90.
21. Houdijk AP, van Lambalgen AA, Thijs LG, van Leeuwen PA. Gut endotoxin restriction improves postoperative hemodynamics in the bile duct-ligated rat. Shock. 1998;9(4):282-8.
22. Vincken S, Reynaert H, Schiettecatte J, Kaufman L, Velkeniers B. Liver cirrhosis and thyroid function: Friend or foe? Acta Clinica Belgica. 2017;72(2):85-90.
23. Chi HC, Chen C-Y, Tsai M-M, Tsai C-Y, Lin K-H. Molecular functions of thyroid hormones and their clinical significance in liver-related diseases. BioMed research international. 2013;2013.
24. Hegedüs L. Thyroid gland volume and thyroid function during and after acute hepatitis infection. Metabolism. 1986;35(6):495-8.
25. Borzio M, Caldara R, Borzio F, Piepoli V, Rampini P, Ferrari C. Thyroid function tests in chronic liver disease: evidence for multiple abnormalities despite clinical euthyroidism. Gut. 1983;24(7):631-6.
26. Dong X, Yang H, Li C, Liu Q, Bai Q, Zhang Z. Triiodothyronine alleviates alcoholic liver disease injury through the negative regulation of the NLRP3 signaling pathway. Experimental and therapeutic medicine. 2018;16(3):1866-72.
27. Chamba A, Neuberger J, Strain A, Hopkins J, Sheppard M, Franklyn J. Expression and function of thyroid hormone receptor variants in normal and chronically diseased human liver. The Journal of Clinical Endocrinology & Metabolism. 1996;81(1):360-7.
28. Kahaly GJ, Dillmann WH. Thyroid hormone action in the heart. Endocrine reviews. 2005;26(5):704-28.
29. Peliciari-Garcia RA, Bargi-Souza P, Young ME, Nunes MT. Repercussions of hypo and hyperthyroidism on the heart circadian clock. Chronobiology international. 2018;35(2):147-59.
30. Bachman ES, Hampton TG, Dhillon H, Amende I, Wang J, Morgan JP, et al. The metabolic and cardiovascular effects of hyperthyroidism are largely independent of β-adrenergic stimulation. Endocrinology. 2004;145(6):2767-74.
31. Lee SS, Marty J, Mantz J, Samain E, Braillon A, Lebrec D. Desensitization of myocardial β‐adrenergic receptors in cirrhotic rats. Hepatology. 1990;12(3):481-5.
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IssueVol 61 No 10 (2023) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/acta.v61i10.15660
Keywords
Chronotropic responses Triiodothyronine Thyroxine T3 resin uptake
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How to Cite
1.
Mohammad Jafari R, Mohammed D, Tavangar SM, Eftekhari G, Shokrian Zeini M, Khodadoostan A, Dehpour AR, Jazaeri F. Effects of Levothyroxine and Liothyronine on Cirrhotic Cardiomyopathy in Rats. Acta Med Iran. 2024;61(10):607-613.