Effect of perfluoroorganic compound emulsion and poloxamer 188 on liver regeneration and the severity of systemic inflammatory response in an experimental model of sepsis
https://doi.org/10.16931/1995-5464.2025-1-48-59
Abstract
Aim. To investigate the effect of perfluoroorganic compounds and poloxamer 188 on liver regeneration and the severity of systemic inflammatory response in an experimental model of sepsis.
Materials and methods. Sepsis was induced in 52 male Wistar rats. Rats in experimental group 1 (n = 16) received a single intravenous injection of Oxiftem, rats in experimental group 2 (n = 15) were injected with Myotiv, and rats in the control group (n = 21) received a 0.9% NaCl solution. An intact group of rats (n = 11) was not subjected to sepsis modeling and received no treatment. Daily observations were conducted for 14 days. On the 15th day, rats were euthanized under light ether anesthesia. Biochemical serum parameters and the results of histological examination of liver tissue with immunohistochemical assessment of CD68 expression were studied.
Results. No abnormalities were observed in the liver parenchyma of the intact group of rats. In the liver of the control group during sepsis, structural alterations of hepatic plates, perinuclear edema of hepatocytes, fatty degeneration of the liver, and congestion of portal tract vessels were noted, indicating morphological manifestations of liver necrosis, as well as proliferation of bile ducts, which is a histological consequence of cholestasis. In the experimental group, preservation of hepatic plate structure, an increase in the total number of nuclei, and binucleated hepatocytes were observed; sinusoids were not dilated. Hepatocyte proliferation and an increase in the number of binucleated liver cells indicated a regenerative response to systemic inflammatory damage and metabolic demand. A reduction in CD68-positive cell content in the liver following administration of both perfluoroorganic compounds and poloxamer 188 may be attributed to the suppression of macrophage activity and phagocytosis. This indicates a blockade of the immune functions of Kupffer cells in the experimental model of sepsis.
Conclusion. The application of perfluoroorganic compounds and poloxamer 188 enhances liver regeneration and reduces the amplitude of systemic inflammatory response reactions in an experimental model of sepsis.
About the Authors
V. Yu. ZiamkoBelarus
Viktoryia Yu. Ziamko – Cand. of Sci. (Med.), Associate Professor, Department of Anesthesiology and Resuscitation with a Course for Advanced Training and Retraining, Vitebsk State Order of Peoples’ Friendship Medical University.
27, Frunze Ave., Vitebsk, 210009
A. M. Dzyadzko
Belarus
Alexander M. Dzyadzko – Doct. of Sci. (Med.), Professor, Head of the Anesthesiology, Resuscitation and Intensive Care Unit, Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology.
8, Semashko str., Minsk, 220045
S. Yu. Pushkin
Russian Federation
Sergey Yu. Pushkin – Director, Medical Emulsions LLC.
31/21, Sovetskaya str., Serpukhov, 142200
E. V. Arshintseva
Russian Federation
Elena V. Arshintseva – Technologist, Medical Emulsions LLC.
31/21, Sovetskaya str., Serpukhov, 142200
O. O. Rummo
Belarus
Oleg O. Rummo – Doct. of Sci. (Med.), Professor, Academician of the National Academy of Sciences of Belarus, Director of the State Institution “Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology”.
8, Semashko str., Minsk, 220045
References
1. Liu V., Escobar G.J., Greene J.D., Soule J., Whippy A., Angus D.C., Iwashyna T.J. Hospital deaths in patients with sepsis from 2 independent cohorts. JAMA. 2014; 312 (1): 90–92. https://doi.org/10.1001/jama.2014.5804
2. Woźnica E.A., Inglot M., Woźnica R.K., Łysenko L. Liver dysfunction in sepsis. Adv. Clin. Exp. Med. 2018; 27 (4): 547–551. https://doi.org/10.17219/acem/68363
3. Singer M., Deutschman C.S., Seymour C.W., Shankar-Hari M., Annane D., Bauer M., Bellomo R., Bernard G.R., Chiche J.D., Coopersmith C.M., Hotchkiss R.S., Levy M.M., Marshall J.C., Martin G.S., Opal S.M., Rubenfeld G.D., van der Poll T., Vincent J.L., Angus D.C. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016; 315 (8): 801–810. https://10.1001/jama.2016.0287.
4. Bauer M., Coldewey S.M., Leitner M., Löffler B., Weis S., Wetzker R. Deterioration of organ function as a hallmark in sepsis: the cellular perspective. Front. Immunol. 2018; 9: 1460. https://doi.org/10.3389/fimmu.2018.01460
5. Srivastava V., Singh S. Organ support in sepsis: a panoramic view from infection to death. Med. J. Armed Forces India. 2024; 80 (1): 4–9. https://doi.org/10.1016/j.mjafi.2023.10.010
6. Huang Y., Zang K., Shang F., Guo S., Gao L., Zhang X. HMGB1 mediates acute liver injury in sepsis through pyroptosis of liver macrophages. Int. J. Burns Trauma. 2020; 10 (3): 60–67.
7. Yan J., Li S., Li S. The role of the liver in sepsis. Int. Rev. Immunol. 2014; 33 (6): 498–510. https://doi.org/10.3109/08830185.2014.889129
8. Koyama Y., Brenner D.A. Liver inflammation and fibrosis. J. Clin. Invest. 2017; 127 (1): 55–64. https://doi.org/10.1172/JCI88881
9. Beyer D., Hoff J., Sommerfeld O., Zipprich A., Gaßler N., Press A.T. The liver in sepsis: molecular mechanism of liver failure and their potential for clinical translation. Mol. Med. 2022; 28 (1): 84. https://doi.org/10.1186/s10020-022-00510-8
10. Dzyadzko A.M., Shcherba A.E., Rummo O.O., Katin M.L., Minov A.F., Korotkov S.V., Chugunova O.A., Santotskii E.O., Efimov D.Y., Gurova M.Y. Paradox: does liver insufficiency protect the patient? A hypothesis. Transplantologiya. The Russian Journal of Transplantation. 2017; 9 (1): 52–70. https://doi.org/10.23873/2074-0506-2017-9-1-52-70 (In Russian)
11. Ziamko V.Yu., Dzyadzko A.M., Shcherba A.E., Pushkin S.Yu., Arshintseva E.V., Grushin V.N. Influence of perfluoroorganic emulsion on morphometric parameters of the liver in a systemic inflammatory response (experimental study). Messenger of Anesthesiology and Resuscitation. 2023; 20 (6): 43–51. https://doi.org/10.24884/2078-5658-2022-20-6-43-51 (In Russian)
12. Rybakova A.V., Makarova M.N., Kukharenko A.E., Vichare A.S., Rueffer F.R. Current requirements for and approaches to dosing in animal studies. The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. 2018; 8 (4): 207–217. https://doi.org/10.30895/1991-2919-2018-8-4-207-217 (In Russian)
13. 2-step plus Poly-HRP Anti Mouse/Rabbit IgG Detection System (with DAB solution). Elabscience; 2024 [updated 19 October 2022; Cited June 3, 2024]. Access mode: https://www.elabscience.com/p-2_step_plus_poly_hrp_anti_mouse_rabbit_igg_detection_system_with_dab_solution_-356126.html
14. Paukov V.S. Patologicheskaya anatomiya: uchebnik [Pathological anatomy. Textbook]. Moscow: GEOTAR-Media, 2021. 736 p. (In Russian)
15. Michalopoulos G.K., Bhushan B. Liver regeneration: biological and pathological mechanisms and implications. Nat. Rev. Gastroenterol. Hepatol. 2021; 18 (1): 40–55. https://doi.org/10.1038/s41575-020-0342-4
16. Michalopoulos G.K. Liver regeneration. J. Cell Physiol. 2007; 213 (2): 286–300. https://doi.org/10.1002/jcp.21172
17. Michalopoulos G.K. Hepatostat: liver regeneration and normal liver tissue maintenance. Hepatology. 2017; 65 (4): 1384–1392. https://doi.org/10.1002/hep.28988
18. Miyaoka Y., Ebato K., Kato H., Arakawa S., Shimizu S., Miyajima A. Hypertrophy and unconventional cell division of hepatocytes underlie liver regeneration. Curr. Biol. 2012; 22 (13): 1166–1175. https://doi.org/10.1016/j.cub.2012.05.016.
19. Dalgatov G.D., Zubritsky V.F., Saburina I.N., Repin V.S., Deev R.V., Zaitseva I.V., Minok M.N., Dalgatova M.A. Cell and roentgen endovascular technologies in combination with regional perfusion with perfluorocarbon emulsions in treatment of chronic diffuse liver diseases. Genes and Cells. 2009; 4 (2): 76–83. (In Russian)
20. Lee Y.A., Wallace M.C., Friedman S.L. Pathobiology of liver fibrosis: a translational success story. Gut. 2015; 64 (5): 830–841. https://doi.org/10.1136/gutjnl-2014-30684
21. Kiseleva Y.V., Zharikov Y.O., Maslennikov R.V., Pavlov C.S., Nikolenko V.N. Molecular factors associated with regression of liver fibrosis of alcoholic etiology. Terapevticheskii Arkhiv. 2021; 93 (2): 204–208. https://doi.org/10.26442/00403660.2021.02.200617 (In Russian)
22. Aydın M.M., Akçalı K.C. Liver fibrosis. Turk. J. Gastroenterol. 2018; 29 (1): 14–21. https://doi.org/10.5152/tjg.2018.17330
23. Zhukova A.G., Sazontova T.G., Arkadyeva I.V., Moroz V.V. The modulating effect of Perfluorane on the ratio of pro- and antioxidative systems in different organs. General Reanimatology. 2006; 1 (3): 7–50. https://doi.org/10.15360/1813-9779-2006-1-47-50 (In Russian)
24. Zyuzya E.V., Volchkova Yu.S., Kalutsky P.V., Ivanov A.V., Pashin E.N. The special features of planimetric parameters of the skin reparative regeneration in simulating an infected wound under the influence of the constant magnetic field and in local introduction of emulsion “Perftoran” and antibacterial drug “Cefotaximum”. Humans and their health. 2013; 1: 11–14. (In Russian)
25. Shevtsov V.I., Martel I.I., Dolganova T.I., Mitin M.M. Perftoran in the treatment of open fractures using the Ilizarov method. Fundamental research. Pharmacology. 2004; 5: 203–205. (In Russian)
26. Kasyanova T.R., Levitan B.N., Titarenko Yu.B. The endothelial dysfunction markers at patients of chronic liver diseases. Kuban Scientific Medical Bulletin. 2012; 3 (132): 70–74. (In Russian)
27. Zubkov I.V., Mashkovtsev O.V., Kosykh A.A., Rasputin G.G. Perfluorocarbon emulsions strenthen the resorption of conjunctuve tissue of the liver after partial hepatectomy in experimental animals with chronic hepatitis. Medical Newsletter of Vyatka. 2003; 1: 35–38. (In Russian)
Supplementary files
Review
For citations:
Ziamko V.Yu., Dzyadzko A.M., Pushkin S.Yu., Arshintseva E.V., Rummo O.O. Effect of perfluoroorganic compound emulsion and poloxamer 188 on liver regeneration and the severity of systemic inflammatory response in an experimental model of sepsis. Annaly khirurgicheskoy gepatologii = Annals of HPB Surgery. 2025;30(1):48-59. (In Russ.) https://doi.org/10.16931/1995-5464.2025-1-48-59