The effect of hyperhomocysteinemia on the patterns of electron microscopic changes in the liver of adult rats

  • Yu. V. Halahan National Pirogov Memorial Medical University, Vinnytsya, Ukraine
  • O. Ye. Maievskyi Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
  • Yu. Yo. Guminskyi National Pirogov Memorial Medical University, Vinnytsya, Ukraine
  • A. P. Korol National Pirogov Memorial Medical University, Vinnytsya, Ukraine
Keywords: adult rats, liver, hyperhomocysteinemia, Kupffer cells, Ito cells.

Abstract

One of the important tasks of modern science is to find biochemical markers that would be able to reflect the risks of development and the nature of the course of various diseases, as well as to predict their possible consequences. In recent years, a significant number of compounds that can affect the biochemical profile of the organism have been identified. Homocysteine – a product of methionine metabolism, belongs to one of these markers, and the effects of its influece on the structure and function of various organs are being actively studied by modern researchers. The aim of the study is to find the patterns of electron microscopic changes in the liver structure of adult rats with hyperhomocysteinemia. The experimental study was performed on 22 white nonlinear mature male rats, which were divided into a control group and an experimental group. A model of persistent hyperhomocysteinemia was created by administering to rats of experimental group 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. In adult rats with experimental hyperhomocysteinemia at the ultrastructural level, dystrophic and destructive changes in hepatocytes, endotheliocytes in the walls of sinusoids and Kupffer cells were found. These changes were more pronounced than in young rats with experimental hyperhomocysteinemia. Revealed structural changes in decompensation (depletion) of mitochondria – fewer number of cristae and enlightened matrix. In contrast to young rats, adult rats with hyperhomocysteinemia in the perisinusoidal spaces showed elongated Ito cells, a significant proportion of the cytoplasm is occupied by the Golgi complex and granular endoplasmic reticulum tanks, indicating protein synthesis for export. In Ito cells, the content of fat droplets, which are located on opposite poles of cells, is reduced. This morphological picture manifests the transformation of Ito cells into fibroblasts.

Downloads

Download data is not yet available.

References

[1] Arutiunian, A. V., Pustyhyna, A. V., Myliutyna, Yu. P., Zalozniaia, I. V., & Kozyna, A. S. (2015). Molecular markers of oxidative stress in offspring with experimental hyperhomocysteinemia. Molecular medicine, (5), 41-46.
[2] Azad, M. A. K., Huang, P., Liu, G., Ren, W., Tekebrh, T., Yan, W., … & Yin, Y. (2018). Hyperhomocysteinemia and cardiovascular disease in animal model. Amino Acids, 50(1), 3-9. doi: 10.1007/s00726-017-2503-5
[3] Dai, H., Wang, W., Tang, X., Chen, R., Chen, Z., Lu, Y., & Yuan, H. (2016). Association between homocysteine and non-alcoholic fatty liver disease in Chinese adults: a cross-sectional study. Nutr J, 15(1), 102. doi: 10.1186/s12937-016-0221-6
[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] Hirase, T., & Node, K. (2012). Endothelial dysfunction as a cellular mechanism for vascular failure. Am J Physiol Heart Circ Physiol, 302(3), 499-505. https://doi.org/10.1152/ajpheart.00325.2011
[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] Hsu, C. C., Cheng, C. H., Hsu, C. L., Lee, W. J., Huang, S. C., & Huang, Y. C. (2015). Role of vitamin B6 status on antioxidant defenses, glutathione and related enzyme activities in mice with homocysteine-induced oxidative stress. Food Nutr Res, 59: 25702. doi: 10.3402/fnr.v59.25702
[8] Huo, Y., Wu, X., Ding, J., Geng, Y., Qiao, W., Ge, A., … & Fan, W. (2018). Vascular Remodeling, Oxidative Stress and Disrupted PPARγ Exspression in Rats of Long-Term Hyperhomocysteinemia with Metabolic Disturbance. PPAR Res, doi: 10.1155/2018/6738703
[9] Jacobs, R. L., Jiang, H., Kennelly, J. P., Orlicky, D. J., Allen, R. H., Stabler, S. P., … & Maclean, K. N. (2017). Cystathione beta-synthase deficiency alters hepatic phospholipid and choline metabolism: post-translation repression of phosphatidylethanolamine N-methyltransferase is a consequence rather than a cause of liver injury in homocysteinuria. Mol Genet Metab, 120(4), 325-336. doi: 10.1016/j.ymgme.2017.02.010
[10] Kovalenko, V. M., Andrushko, I. I., & Talaieva, T. V. (2011). Association of hyperhomocysteinemia with metabolic risk factors in patients with coronary heart disease. Ukrainian Journal of Cardiology, (6), 66-70.
[11] Kychyhyna, O. N., Holubeva, T. I., Troshyna, I. A., & Romanova, N. V. (2015). Pathogenetic significance of hyperhomocysteinemia in non-alcoholic fatty liver disease. Medical science and education of the Urals, 3(38), 177-182.
[12] 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.
[13] Melnyk, A. V., & Zaichko, N. V. (2017). Gender features of the influence of hyperhomocysteinemia on the metabolism of sulfur-containing amino acids and hydrogen sulfide in the liver. Medical and clinical chemistry, 1 (19), 95-101.
[14] Nekrut, D. O. (2016). The effect of hyperhomocysteinemia on the formation of nonalcoholic fatty liver disease in rats. Bulletin of morphology, 22(1), 40-45.
[15] 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.
[16] 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
[17] 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.
[18] Tsybykov, N. N., Tereshkov, P. P., Sepp, A. V., & Yzmestev, S. V. (2015). The mechanism of hypercoagulation in experimental hyperhomocysteinemia. Thrombosis, hemostasis, rheology, 4(64), 27-30.
[19] Yang, A., Jiao, Y., Yang, S., Deng, M., Yang, X., Mao, C., … & Jiang, Y. (2018). Homocysteine activates autophagy by inhibition of CFTR expression via interaction between DNA methylation and H3K27me3 in mouse liver. Cell Death Dis, 92(2), 169-182. doi: 10.1038/s41419-017-0216-z
[20] Zaichko, N. V., Lutsiuk, M. B., & Hryhorieva, G. O. (2012). Hyperhomocysteinemia: medical, social and pharmacological aspects. Pharmaceutical courier, 9, 30-35.
[21] Zobova, D. A., & Kozlov, S. A. (2016). The role of homocysteine in the pathogenesis of certain diseases. Medical sciences, 3(39), 132-144.
Published
2020-07-10
How to Cite
Halahan, Y. V., Maievskyi, O. Y., Guminskyi, Y. Y., & Korol, A. P. (2020). The effect of hyperhomocysteinemia on the patterns of electron microscopic changes in the liver of adult rats. Biomedical and Biosocial Anthropology, (36), 16-21. https://doi.org/10.31393/bba36-2019-03