THE METABOLISM OF GLUCOSE AS THE MAIN ENERGY SUBSTRATE OF HEPATOCYTES IN DIFFERENT METHODS OF LIVER PRESERVATION
Abstract
Background. Maintaining energy balance in hepatocytes is an important aspect of liver graft preservation. Objective – to conduct a comparative study of the effects of static cold storage and hypothermic oxygenated machine perfusion of liver grafts on the metabolism of glucose as the main energy substrate of hepatocytes. Material and methods. In this prospective case-control study (with marginal liver grafts splitting into two halves) we conducted a comparative analysis of the effects of static cold preservation and hypothermic oxygenated machine perfusion of liver transplants on the metabolism of glucose as the main energy substrate of liver cells using biochemical, morphological and immunohistochemical methods. Results. It has been shown that the use of hypothermic oxygenated machine perfusion is characterized by significantly lower values of the ratio of lactate to glucose in the effluent after 2 and 4 hours of perfusion and significantly lower values of the expression of glucose transporter molecules GLUT1 on hepatocyte membranes in comparison with static cold preservation. Conclusions. The use of hypothermic oxygenated machine perfusion even in marginal grafts allows to restore the respiratory chain in mitochondria and aerobic glycolysis enzymes of liver cells.References
1. Van den Berghe G. The role of the liver in metabolic homeostasis: implications for inborn errors of metabolism. JIMD. 1991;14(4):407-420. https://doi.org/10.1007/BF01797914.
2. Gomez-Lechon MJ, Donato MT, Castell JV, Jover R. Human hepatocytes as a tool for studying toxicity and drug metabolism. Curr. Drug Metab. 2003;4(4):292-312. https://doi.org/10.2174/1389200033489424.
3. Kamiyama Y, Takeda H, Ohshita M, Nambu H, Yamaoka Y. Hepatic metabolic changes following energy deprivation by ammonia in patients and rabbits with jaundice. Surg. Gynecol. Obstet. 1977;145(1):33-40.
4. Watanabe F, Kamiike W, Nishimura T, Hashimoto T, Tagawa K. Decrease in mitochondrial levels of adenine nucleotides and concomitant mitochondrial dysfunction in ischemic rat liver. J. Biochem. 1983;94(2):493-499. https://doi.org/10.1093/oxfordjournals.jbchem.a134380.
5. Harvey PR, Iu S, McKeown CM, Petrunka CN, Ilson RG, Strasberg SM. Adenine nucleotide tissue concentrations and liver allograft viability after cold preservation and warm ischemia. Transplantation. 1988;45(6):1016-1020. https://doi.org/10.1097/00007890-198806000-00004.
6. Belzer FO, Southard JH. Principles of solid-organ preservation by cold storage. Transplantation. 1988;45(4):673-676. https://doi.org/10.1097/00007890-198804000-00001.
7. Koolman J, Roehm KH. Color Atlas of Biochemistry. 2nd ed. Stuttgart, New York: Thieme; 2005. 476 p.
8. Taylor MJ. Biology of cell survival in the cold: The basis for biopreservation of tissues and organs. In: Baust JG, Baust JM, editors. Advances in biopreservation. Boca Raton: Taylor Francis Group; 2006. p. 15-62. https://doi.org/10.1201/9781420004229.ch2.
9. Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell biology of ischemia/reperfusion injury. Int. Rev. Cell. Mol. Biol. 2012;298:229-317. https://doi.org/10.1016/B978-0-12-394309-5.00006-7.
10. Nowak G, Ungerstedt J, Wernerman J, Ungerstedt U, Ericzon BG. Metabolic changes in the liver graft monitored continuously with microdialysis during liver transplantation in a pig model. Liver Transpl. 2002;8(5):424-432. https://doi.org/10.1053/jlts.2002.32943.
11. Cave AC, Ingwall JS, Friedrich J, Liao R, Saupe KW, Apstein CS, Eberli FR. ATP synthesis during low-flow ischemia: influence of increased glycolytic substrate. Circulation. 2000;101(17):2090-2096.
12. Eberli FR, Weinberg EO, Grice WN, Horowitz GL, Apstein CS. Protective effect of increased glycolytic substrate against systolic and diastolic dysfunction and increased coronary resistance from prolonged global underperfusion and reperfusion in isolated rabbit hearts perfused with erythrocyte suspensions. Circ Res. 1991;68(2):466-481.
