Changes in the histostructure of the lungs of old rats under conditions of persistent hyperhomocysteinemia

  • I. A. Samborska National Pirogov Memorial Medical University, Vinnytsya, Ukraine
Keywords: hyperhomocysteinemia, atelectasis, emphysema, sclerosis.


To date, homocysteine has been found to be an important biomarker of bronchopulmonary pathology, including COPD. The increase in its concentration in the blood plasma causes the start of free radical processes and the production of reactive oxygen species, which activate lipid peroxidation in lung tissue. In addition, the activation of endoplasmic reticulum stress with increasing homocysteine levels is the main reason for triggering apoptosis of alveolocytes. The aim of the research is to study the features of lungs histostructure in old rats under conditions of hyperhomocysteinemia. The experimental study was performed on 20 white nonlinear old (24-26 months) male rats. During the experiment, the animals were divided into two groups – control and experimental. Simulation of the state of persistent hyperhomocysteinemia was achieved by administering to rats of experimental group thiolactone homocysteine at a dose of 200 mg/kg body weight intragastrally for 60 days. Histological specimens were studied using an SEO CCAN light microscope and photo-documented using a Vision CCD Camera with an image output system from histological specimens. In elderly animals under conditions of experimental hyperhomocysteinemia develop severe destructive-degenerative changes in the lungs. Significant remodeling of the vascular bed, bronchi, inflammatory manifestations, enlargement of dis- and atelectasis and emphysematically altered alveoli of the respiratory lungs, violation of the alveolar walls, with the release of blood cells into the alveolar space and the formation of small diapedetic hemorrhages. The development of perivascular, peribronchial and interstitial sclerosis is characteristic.


[1] 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
[2] Bahrii, M. M., Dibrova, V. A., Popadynets, O. H. & Hryshchuk, M. I. (2016). Методики морфологічних досліджень [Methods of morphological research]. Вінниця: Нова Книга – Vinnytsia: New Book.
[3] Behera, J., Tyagi, S. C., & Tyagi, N. (2019). Hyperhomocysteinemia induced endothelial progenitor cells dysfunction through hypermethylation of CBS promoter. Biochem Biophys Res Commun, 510(1), 135-141. doi: 10.1016/j.bbrc.2019.01.066
[4] Burdenny`j, A. M., Loginov, V. I., Zavary`kina, T. M., Braga, E`. A., & Kubatiev, A. A. (2017). Молекулярно-генетические нарушения генов фолатного и гомоцистеинового обмена в патогенезе ряда многофакторных заболеваний [Molecular genetic disorders of folate and homocysteine metabolism genes in the pathogenesis of a number of multifactorial diseases]. Генетика – Genetics, 53(5), 526-540.
[5] Chen, Y., Zhang, H., Liu, E., Xu, C., & Zhang, Y. (2016). Homocysteine regulates endothelin type B receptors in vascular smooth muscle cells. Vascul Pharmacol, (87), 100-109. doi: 10.1016/j.vph.2016.08.011
[6] Dobrelia, N. V., Boitsova, L. V. & Danova, I. V. (2015). Правова база для проведення етичної експертизи доклінічних досліджень лікарських засобів з використанням лабораторних тварин [Legal basis for ethical examination of preclinical studies of drugs using laboratory animals]. Фармакологія та лікарська токсикологія – Pharmacology and drug toxicology, (2), 95-100.
[7] 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
[8] He, Y., Liu, S., Zhang, Z., Liao, C., Lin, F., Yao, W., … & Chen, Y. (2017). Imbalance of endogenous hydrogen sulfide and homocysteine in chronic obstructive pulmonary disease combined with cardiovascular disease. Front Pharmacol, (8), 624. doi: 10.3389/fphar.2017.00624
[9] Hiraoka, M., & Kagawa, Y. (2017). Genetic polymorphisms and folate status. Congenit Anom (Kyoto), 57(5), 142-149. doi: 10.1111/cga.12232
[10] Horalskyi, L. P., Khomych, V. T., & Kononskyi, O. I. (2011). Основи гістологічної техніки і морфофункціональні методи досліджень у нормі та при патології [Fundamentals of histological technique and morphofunctional research methods in normal and pathology]. Житомир: Полісся – Zhytomyr: Polissya.
[11] Jakubowski, H. (2019). Homocysteine modification in protein structure / function and human disease. Physiol Rev, 99(1), 555-604. doi: 10.1152/physrev.00003.2018
[12] Khan, N. A., Saini, H., Mawari, G., Kumar, S., Hira, H. S., & Daga, M. K. (2016). The effect of folic acid supplementation on hyperhomocysteinemia and pulmonary function parameters in chronic obstructive pulmonary disease: a pilot study. J Clin Diagn Res, 10(11), 17-21. doi: 10.7860/JCDR/2016/21322.8927
[13] Kim, J., Kim, H., Roh, H., & Kwon, Y. (2018). Causes of hyperhomocysteinemia and its pathological significance. Arch Pharm Res, 41(4), 372-383. doi: 10.1007/s12272-018-1016-4
[14] Liu, Z., Wang, H., Guan, L., & Zhao, B. (2015). Regulatory effects of hydrogen sulfide on alveolar epithelial cell endoplasmic reticulum stress in rats with acute lung injury. World J Emerg Med, 6(1), 67-73. doi: 10.5847/wjem.j.1920-8642.2015.01.012
[15] Lutsiuk, M. B., Zaichko, N. V., Hryhorieva, H. S., Konakhovych, M. A., Artemchuk, M. A., Pentiuk, N. O., … & Postovitenko, K. P. (2013). Синдром гіпергомоцистеїнемії: причини виникнення, способи профілактики та лікування [Hyperhomocysteinemia syndrome: causes, methods of prevention and treatment]. Рациональная фармакотерапия – Rational pharmacotherapy, 29(4), 55-60.
[16] Medvedev, D. V., Zvyagina, V. I., & Fomina, M. A. (2014). Способ моделирования тяжелой формы гипергомоцистеинемии у крыс [Method for modeling severe hyperhomocysteinemia in rats]. Российский медико-биологический вестник имени академика И. П. Павлова – Russian medical and biological bulletin named after academician I.P. Pavlov, (4), 42-46.
[17] Moretti, R. (2019). Homocysteine: new aspects of an ancient enigma. Cardiology, 144(1-2), 36-39. doi: 10.1159/000501997
[18] Nakano, H., Inoue, S., Igarashi, A., Tokairin, Y., Yamauchi, K., Kimura, T., … & Shibata, Y. (2021). Effect of hyperhomocysteinemia on a murine model of smoke-indiced pulmonary emphysema. Research Square. https: doi: 10.21203/rs.3rs-249722/v1
[19] Silla, Y., Varshney, S., Ray, A., Basak, T., Zinelly, A., Sabaresh, V., … & Sengupta, S. (2019). Hydrolysis of homocysteine thiolactone results in the formation of protein-cys-S-S-homocysteinylation. Proteins, 87(8), 625-634. doi: 10.1002/prot.25681
[20] Yang, J., Li, H., Deng, H., & Wang, Z. (2018). Association of one-carbon metabolism-related vitamins (folate, B6, B12) homocysteine and methionine with the risk of lung cancer: systematic review and meta-analysis. Front Oncol, (8), 493. doi: 10.3389/fonc.2018.00493
[21] Zaichko, N. V., Lutsiuk, M. B., & Hryhorieva, H. O. (2012). Гіпергомоцистеїнемія: медико-соціальні та фармакологічні аспекти [Hyperhomocysteinemia: medical, social and pharmacological aspects]. Фармацевтичний кур’єр – Pharmaceutical courier, (9), 30-35.
How to Cite
Samborska , I. A. (2020). Changes in the histostructure of the lungs of old rats under conditions of persistent hyperhomocysteinemia. Biomedical and Biosocial Anthropology, (41), 41-45.