Contribution of mitochondrial therapy to processes of regeneration and self-organization of the cell system of the resected liver in rats

Автор: Kit Oleg I., Shikhlyarova Alla I., Frantsiyants Elena M., Neskubina Irina V., Kaplieva Irina V., Bandovkina Valeriya A., Engibaryan Marina A., Przhdetskiy Yuriy V., Trepitaki Lidia K., Pogorelova Yulia A., Zhukova Galina V., Popov Ivan A., Cheryarina Natalia D., Shlyk Sergey V., Kotieva Inga M., Kuchkina Lyudmila P., Luganskaya Roza G., Kovalenko Vera A.

Журнал: Cardiometry @cardiometry

Статья в выпуске: 24, 2022 года.

Бесплатный доступ

Topicality. Studies of the processes of the regeneration in the liver are not new, but however the development of the technologies of bio-therapy is capable of shifting the conventional approaches to the regeneration of the lost tissues. Mitochondrial therapy (MCT) occupies one of the highly important places in the list of bio-technologies by offering some unique mechanisms of the restoration of the organs. The liver having its specific tissue property of the regeneration demonstrates upon completion of hepatoectomy mitochondrial insufficiency and inhibition of the regenerative processes. Therefore it is required to evaluate the efficacy of mitochondrial stimulation in an experimental model in vivo with the proper morphological confirmation of the productivity and acceleration of the regenerative function of the liver that has become decisive for our research study work. Materials and methods. We have resected in 30 albino outbred male rats the left lobe of the liver, which is the maximum tolerable volume, amounting to 70% of the total mass of this organ, and upon of expiration of 24 hours we have transplanted to them intraperitoneally mitochondria harvested from a donor rat. Mitochondria have been isolated with the use of the differential centrifugation with high-speed refrigerated centrifuge Avanti J-E, BECMAN COULTER, USA. The morphological ORIGINAL RESEARCH examination of the liver sections has been conducted after their embedding in paraffin wax and staining with hematoxylin-eosin using microscopic testing of the liver sections with Axiovert (Carl 44 Zeiss, Germany) and applying the visualization software Axiovision 4 (Carl Zeiss, Germany). Results and discussion. It has been established that within the same period of time the quantitative data on the mass of the liver and its stump after MCT have exceeded the respective reference data by a factor of 1,6 (р˂0,05). The efficacy of the MCT application with respect to the regenerative function of the liver has been confirmed by the quality of the hepatic self-organization and replenishment of the key structures. A considerable supply of the most important cell elements of the connective tissue to the capsulated zone of the stump of the liver, an activation of neo-angiogenesis, hyperplasia and hypertrophy of hepatocytes with the repetitive order of the arrangement of the lobe structure of full value are manifestations of the acceleration of the regeneration. Conclusion. The high energy potential of fresh mitochondria makes possible to realize the trigger mechanisms of the bio-synthetic processes addressing an immediate restoration of the damaged or disordered liver tissues that can hold the greatest promise in emergency surgery and the activation of slowly progressive processes.

Еще

Regeneration, liver morphology, mitochondria, resection of liver lobe, hepatocytes, mitochondrial therapy

Короткий адрес: https://sciup.org/148326587

IDR: 148326587   |   DOI: 10.18137/cardiometry.2022.24.99105

Список литературы Contribution of mitochondrial therapy to processes of regeneration and self-organization of the cell system of the resected liver in rats

  • Gadd VL., Aleksieva N., Forbes SJ. Epithelial plasticity during liver injury and regeneration. Cell Stem Cell. 2020;27:557–573. doi: 10.1016/j.stem.2020.08.016.
  • Pu W., Zhou B. Hepatocyte generation in liver homeostasis, repair, and regeneration. Cell Regen. 2022;11(1):2. doi: 10.1186/s13619-021-00101-8.
  • Yu F. X., Zhao B., Guan K. L. Hippo pathway in organ size control, tissue homeostasis, and cancer. Cell. 2015;163(4):811–828. doi: 10.1016/j.cell.2015.10.044.
  • Rudnick D. A., Davidson N. O. Functional relationships between lipid metabolism and liver regeneration. International Journal Hepatology. 2012;2012, article 549241:8. doi: 10.1155/2012/549241.
  • Trefts E., Gannon M., Wasserman DH. The liver. Curr Biol. 2017;27(21):R1147-R1151. doi: 10.1016/j.cub.2017.09.019.
  • Sies H., Jones DP. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol. 2020;21(7):363-383. doi: 10.1038/s41580-020-0230-3.
  • Huang W., et al. A narrative review of liver regeneration – from models to molecular basis. Ann Transl Med. 2021;9(22):1705. doi: 10.21037/atm-21-5234.
  • Huang J., Rudnick DA. Elucidating the metabolic regulation of liver regeneration. Am J Pathol. 2014;184(2):309-21. doi: 10.1016/j.ajpath.2013.04.034.
  • Zhu R., Wang Y., Zhang L., Guo Q. Oxidative stress and liver disease. Hepatol Res. 2012;42(8):741-9. doi: 10.1111/j.1872-034X.2012.00996.x.
  • Fazel Modares N., Polz R., Haghighi F., Lamertz L., Behnke K., Zhuang Y., et al. IL‐6 trans‐signaling controls liver regeneration after partial hepatectomy. Hepatology. 2019;70:2075–91. doi: 10.1002/hep.30774.
  • Chae MS, Moon KU, Chung HS, Park CS, Lee J, Choi JH, et al. Serum interleukin‐6 and tumor necrosis factor‐α are associated with early graft regeneration after living donor liver transplantation. PLoS ONE. 2018;13:1 doi:10.1371/journal.pone.0195262.
  • Ishimaru M., et al. Purinergic signaling via P2Y receptors up‐mediates IL‐6 production by liver macrophages/Kupffer cells. J Toxicol Sci. 2014;39:413–23. doi: 10.2131/jts.39.413.
  • Frantsiyants EM, et al. Content of apoptosis factors and self-organization processes in the mitochondria of heart cells in female mice C57BL/6 under growth of melanoma B16/F10 linked with comorbid pathology. Cardiometry. 2021:18:121-130. doi: 10.18137/cardiometry.2021.18.121130.
  • Frantsiyants EM, et al. The functional state of mitochondria of cardiomyocytes in a malignant process against the background of comorbid pathology in the experiment. South Russian Journal of Oncology. 2021;2(3):13-22. doi: 10.37748/2686-9039-2021-2-3-2.[in Russian]
  • Wang P., Jia J., Zhang D. Purinergic signaling in liver diseases: pathological functions and therapeutic opportunities. J Hepatol Rep. 2020;2:1–15. doi: 10.1016/j.jhepr.2020.100165.
  • Alexandrino H., Rolo A., Teodoro JS., Donato H., Martins R., Serôdio M., et al. Bioenergetic adaptations of the human liver in the ALPPS procedure—how liver regeneration correlates with mitochondrial energy status. HPB (Oxford). 2017;19:1091–103. doi: 10.1016/j.hpb.2017.08.005.
  • Alexandrino H., et al. Mitochondrial bioenergetics and posthepatectomy liver dysfunction. Eur J Clin Invest. 2016;46(7):627-35. doi: 10.1111/eci.12639.
  • Kit O.I., et al. Mitochondrial therapy: direct visual assessment of the possibility of preventing myocardial infarction under chronic neurogenic pain and B16 melanoma growth in the experiment. Cardiometry. 2022; 22:38-49. doi: 10.18137/cardiometry.2022.22.3849.
  • Kit O.I., et al. Biological effects of mitochondrial therapy: preventing development of myocardial infarction and blocking metastatic aggression of B16/ F10 melanoma. Cardiometry. 2022; 22:50-55. doi: 10.18137/cardiometry.2022.22.3849.
  • Egorova M.V., Afanasiev S.A. Isolation of mitochondria from cells and tissues of animals and humans: Modern methodological techniques. Siberian Medical Journal. 2011;26(1-1):22-28. [in Russian]
Еще
Статья научная