Submicroscopic changes in the liver of young rats with hyperhomocysteinemia

  • Yu.V. Halahan National Pirogov Memorial Medical University, Vinnytsya, Ukraine
Keywords: hyperhomocysteinemia, hepatocytes, mitochondria, macrophages, sinusoidal capillaries.

Abstract

To date, it has been established that hyperhomocysteinemia plays a significant role in the development and progression of many diseases. The accumulation of homocysteine occurs due to a violation of the relationship between its production and excretion from the body. The liver plays an important role in the metabolism of homocysteine, because it undergoes most of the reactions of its transmethylation, and, therefore, it is the first to be adversely affected. The aim of the study is to identify the features of electron microscopic changes in the liver structure of young rats with hyperhomocysteinemia. The experimental study was performed on 22 white nonlinear young (1-2 months) male rats, which were divided into a control group and an experimental group. A model of persistent hyperhomocysteinemia was created by administering to rats the experimental group of thiolactone homocysteine at a dose of 200 mg/kg body weight intragastrically for 60 days. The study of ultrastructural changes in the liver of rats was performed using an electron microscope PEM-125K. It was found that the introduction of thiolactone homocysteine at a dose of 200 mg/kg in rats led to the development of degenerative changes in hepatocytes. Changes in the structure of liver cells manifested themselves in the form of edema of the cytoplasm and mitochondria, destruction of mitochondrial cristae, dilation of the tubules of the granular endoplasmic reticulum and tanks of the Golgi complex. The activity of fat-accumulating liver cells and stellate macrophages is characteristically. In the lumens of the sinusoidal capillaries found sweeter shaped blood elements, the cytoplasm of endothelial cells had signs of edema. Thus, in experimental hyperhomocysteinemia revealed changes at the ultrastructural level in all structural components of the liver of young rats. The identified changes are compensatory-adaptive in nature and are reversible.

Downloads

Download data is not yet available.

References

[1] Ahn, C. W., Jun, D. S., Na, J. D., Choi, Y. J., & Kim, Y. C. (2016). Alleviation of hepatic fat accumulation by betaine involves reduction of homocysteine methyltransferase (BHMT). Biochem. Biophys. Res. Commun., 477(3), 440-447. doi: 10.1016/j.bbrc.2016.06.080
[2] 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. doi: 10.3390/nu9040346
[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. doi: 10.3164/jcbn.15-54
[4] Faversani, J. L., Hammerschmidt, T. G., Sitta, A., Deon, M., Wajner, M., & Vargas, C. R. (2017). Oxidative Stress in Homocysteinuria Due to Cystathione β-synthase Deficiency: Findings in Patients and in Animal Model. Cell Mol. Neurobiol., 37(8), 1477-1485. doi: 10.1007/s10571-017-0478-0
[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] Horalskyi, L. P., Khomych, V. T., & Kononskyi, O. I. (2011). Fundamentals of histological technique and morphofunctional research methods in normal and pathology. Zhytomyr: Polissya.
[7] Jeon, J. S., Oh, J. J., Kwak, H. C., Yun, H. Y., Kim, H. C., Kim, Y. M., … Kim, S. K. (2018). Age-Related Changes in Sulfur Amino Acid Metabolism in Male C57BL/6 Mice. Biomol. Ther. (Seoul)., 26(2), 167-174. doi: 10.4062/biomolther.2017.054
[8] Lai, W. K., & Kan, M. Y. (2015). Homocysteine-induced endothelial dysfunction. Ann. Nutr. Metab., 67(1), 1-12. doi: 10.1159/000437098
[9] Lutsiuk, M. B., Zaichko, N. V., Hryhorieva, G. S., Konakhovych, M. A., Artemchuk, M. A., Pentiuk, N. O., & Postovitenko, K. P. (2013). Hyperhomocysteinemia syndrome: causes, methods of prevention and treatment. Rational pharmacotherapy, 29(4), 55-60.
[10] Medvedev, D. V., & Zviahyna, V. I. (2016). Study of biochemical mechanisms of development of hepatocyte mitochondrial dysfunction in experimental hyperhomocysteinemia in rats. Nutrition issues, 85(1), 29-35.
[11] 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.
[12] Novohrodskaia, Ya. I., Kravchuk, R. I., Ostrovskaia, O. B., & Kurbat, M. N. (2019). Morphological changes in the liver of rats with hyperhomocysteinemia. Hepatology and Gastroenterology, 3(1), 93-98.
[13] Orlovskyi, V. F., & Kuchma, N. G. (2015). Effect of correction of hyperhomocysteinemia on functional liver tests and lipid profile in patients with nonalcoholic fatty liver disease in combination with diabetes mellitus. International Journal of Endocrinology, 5(69), 31-34.
[14] Pacana, T., Cazanave, S., Verdianelli, A., Patel, V., Min, H. K., Mirshahi, F., … Sanyal, A. S. (2015). Dysregulated Hepatic Methionine Metabolism Drives Homocysteine Elevation in Diet-Induced Nonalcoholic Fatty Liver Disease. PLoS One, 10(8): e0136822. doi: 10.1371/journal.pone.0136822
[15] Pentiuk, O. O., Lutsiuk, M. B., & Artemchuk, M. A. (2007). Preclinical studies of hyperhomocysteinemic action of potential drugs. К.: State Pharmacological Center of the Ministry of Health of Ukraine.
[16] Skovierova, H., Vidomanova, E., Mahmood, S., Sopkova, J., Drgova, A., Cervenova, T., … Lehotsky, J. (2016). The molecular and cellular effect of homocysteine metabolism imbalance on human health. Int. J. Mol. Sci., 17(10), 1733. doi: 10.3390/ijms17101733
[17] Vlasenko, A. V. (2013). The effect of hyperhomocysteinemia on the development of non-alcoholic fatty liver disease in diabetes mellitus. International Endocrinological Journal, 1(49), 10-14.
[18] Zaichko, N. V. (2010). Plasma levels of homocysteine, cysteine, and hydrogen sulfide in patients with lower extremity deep vein thrombosis: association with C677T polymorphism in the methylenetetrahydrofolate reductase gene. Experimental and Clinical Physiology and Biochemistry, 4, 35-41.
[19] Zaichko, N. V., Lutsiuk, M. B., & Hryhorieva, G. O. (2012). Hyperhomocysteinemia: medical, social and pharmacological aspects. Pharmaceutical Courier, 9, 30-35.
[20] Zviahyntseva, T. D., & Glushchenko, S. V. (2018). The role of mitochondrial dysfunction in the development of non-alcoholic fatty liver disease. Experimental and Clinical Gastroenterology, 150(2), 37-43.
[21] Zviahyntseva, T. D., Chernobai, A. I., & Glushchenko, S. V. (2014). The role of ademetionine in the development and progression of chronic liver diseases. Ukrainian Medical Journal, 3(101), 56-59.
Published
2020-02-28
How to Cite
Halahan, Y. (2020). Submicroscopic changes in the liver of young rats with hyperhomocysteinemia. Reports of Morphology, 26(1), 19-23. https://doi.org/10.31393/morphology-journal-2020-26(1)-03