Morphological changes of the liver under conditions of hyperhomocysteinemia in the background of hypo- and hyperthyroidism


  • V.M. Nechyporuk National Pirogov Memorial Medical University, Vinnytsia, Ukraine
  • M.M. Korda I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine
  • O.V. Kovalchuk National Pirogov Memorial Medical University, Vinnytsia, Ukraine
Keywords: hyperthyroidism, hypothyroidism, hyperhomocysteinemia, homocysteine, liver.

Abstract

Thyroxine and Triiodothyronine are very important for normal growth, development and organ function. These hormones regulate the basal rate of metabolism of all cells, including hepatocytes, and thus modulate liver function. There is a close connection between hyperhomocysteinemia (HHCy) and the induction of oxidative processes, disruption of nitric oxide production of NO synthase, damage to the endoplasmic reticulum and activation of inflammatory processes in the liver. Disorders of homocysteine metabolism (HC) in thyroid dysfunction are also known. Therefore, it can be assumed that the violation of the structure and functions of the liver will be an important manifestation of the negative impact of HHCy on organs and tissues in hyper- and hypothyroidism. The aim of the study was to establish the reorganization of the structural components of the liver in the conditions of modelized HHCy, hyper- and hypothyroidism and their joint effects. Thiolactone HHCy was modelized by administering to animals an exogenous HC in the form of Thiolactone at a dose of 100 mg/kg body weight once a day for 28 days. Hyperthyroidism was modelized by daily administration of L-thyroxine at a dose of 200 μg/kg for the 21 days, hypothyroidism - daily administration of Thiamazole at a dose of 10 mg/kg for the 21 days. Individual groups of animals were administered L-thyroxine and Thiamazole in parallel with HC. It was found that in the conditions of simulated HHCy, hypo- and hyperthyroidism in the liver of experimental animals there is an incompleteness of hepatocyte beams, changes in hepatocytes of destructive, dystrophic and necrotic nature with signs of steatosis, vascular disorders. Conclusions: both HHCy and hypo- or hyperthyroidism lead to a violation of the structural organization of liver tissue. With the development of thyroid dysfunction on the background of HHCy, the disturbances of the histological structure of hepatocytes significantly increased.

References

[1] Ai, Y., Sun, Z., Peng, C., Liu, L., Xiao, X., & Li, J. (2017). Homocysteine Induces Hepatic Steatosis Involving ER Stress Response in High Methionine Diet-Fed Mice. Nutrients, 9(4), E346. https://doi:10.3390/nu9040346

[2] Campbell, N., Agarwal, K., Alidoost, M., Miskoff, J.A., & Hossain M. (2020). Acute Fulminant Hepatic Failure and Renal Failure Induced by Oral Amiodarone: A Case Report and Literature Review. Cureus, 12(5), e8311. https://doi:10.7759/cureus.8311

[3] Dai, Y., Zhu, J., Meng, D., Yu, C., & Li, Y. (2016). Association of homocysteine level with biopsy-proven non-alcoholic fatty liver disease: a meta-analysis. J. Clin. Biochem. Nutr., 58(1), 76-83. https://doi.org:10.3164/jcbn.15-54

[4] De Leo, S., Lee, S.Y., & Braverman, L.E. (2016). Hyperthyroidism. Lancet (London, England), 388(10047), 906-918. https://doi.org/10.1016/S0140-6736(16)00278-6

[5] Glushchenko, S. V. (2014). Hyperhomocysteinemia as a predictor of the development and progression of fatty liver disease. Problems of Сontinuing Medical Education and Science, 2, 89-92.

[6] Gomez-Peralta, F., Velasco-Martínez, P., Abreu, C., Cepeda, M., & Fernández-Puente, M. (2018). Hepatotoxicity in hyperthyroid patient after consecutive methimazole and propylthiouracil therapies. Endocrinology, diabetes & metabolism case reports, 2018, 17-0173. https://doi.org/10.1530/EDM-17-0173

[7] Goralskiy, L. P., Homich, V. Т., & Kononskiy, О. І. (2011). Fundamentals of histological technique and morphofunctional methods of research in norm and in pathology. Zhitomir: Polissya.

[8] Hu, Y., Liu, J., Dong, X., Xu, Y., Leng, S., & Wang, G. (2016). Clinical Study of Serum Homocysteine and Non-Alcoholic Fatty Liver Disease in Euglycemic Patients. Medical science monitor : international medical journal of experimental and clinical research, 22, 4146-4151. https://doi.org/10.12659/msm.897924

[9] Lai, W. K., & Kan, M. Y. (2015). Homocysteine-induced endothelial dysfunction. Ann. Nutr. Metab., 67(1), 1-12. https://doi:10.1159/000437098

[10] Makarova, N. G., Vasilyeva, L. S., & Garmaeva, D. V. (2010). Structure of liver in experimental hypothyreos. Siberian Medical Journal, 94(3), 70-73.

[11] Martínez, Y., Li, X., Liu, G., Bin, P., Yan, W., Más, D., … & Yin Y. (2017). The role of methionine on metabolism, oxidative stress, and diseases. Amino Acids, 49(12), 2091-2098. doi: 10.1007/s00726-017-2494-2. PMID: 28929442

[12] Mato, J. M., Alonso, C., Noureddin, M., & Lu, S. C. (2019). Biomarkers and subtypes of deranged lipid metabolism in non-alcoholic fatty liver disease. World J. Gastroenterol., 25(24), 3009-3020. https://doi:10.3748/wjg.v25.i24.3009 PMID: 31293337

[13] Nadkharni, N., Masoodi, I., Ahmari, A., Sirwal, T., & Malik, N. (2018). Hyperthyroidism induced reversible hepatotoxicity a case report and brief review. International. Journal of Medical Science and Public Health, 7, 1. https://doi:10.5455/ijmsph.2018.0823817082018

[14] Nechiporuk, V., & Korda, M. (2017). Metabolism of cysteine in experimental hyper- and hypothyroidism in rats. Medical and Clinical Chemistry, 19(4), 32-40. https://doi:10.11603/mcch.2410-681X.2017.v0.i4.8433

[15] Nechiporuk, V., Zaichko, N., Korda, М., Melnyk, A., & Koloshko, O. (2017). Sulphur-containing amino acids metabolism in experimental hyper- and hypothyroidism in rats. Georgian medical news. 96-102.

[16] Nekrut, D. O., Zaichko, N. V., & Korol, A. P. (2017). Effect of hypolipidemic agents on morphological changes in rat liver in nonalcoholic fatty liver disease associated with hyperhomocysteinemia. Biomedical and Biosocial Anthropology, 28, 66-71.

[17] Perła-Kaján, J., & Jakubowski, H. (2019). Dysregulation of Epigenetic Mechanisms of Gene Expression in the Pathologies of Hyperhomocysteinemia. International journal of molecular sciences, 20(13), 3140. https://doi.org/10.3390/ijms20133140

[18] Shetty, S., Rajasekaran, S., & Venkatakrishnan, L. (2014). Grave’s Disease and Primary Biliary Cirrhosis-An Unusual and Challenging Association. Journal of clinical and experimental hepatology, 4(1), 66-67. https://doi.org/10.1016/j.jceh.2013.08.001

[19] Stangl, G. I. (2007). Homocysteine thiolactone-induced hyperhomocysteinemia does not alter concentrations of cholesterol and SREBP-2 target gene mRNAS in rats. Exp. Biol. Med., 232(1), 81-87.
Published
2020-10-12
How to Cite
Nechyporuk, V., Korda, M., & Kovalchuk, O. (2020). Morphological changes of the liver under conditions of hyperhomocysteinemia in the background of hypo- and hyperthyroidism. Reports of Morphology, 26(2), 19-25. https://doi.org/https://doi.org/10.31393/morphology-journal-2020-26(2)-03