Comparative analysis of the effects of various detoxification solutions on the structure of the kidneys in experimental burn disease in rats
The use of existing infusion solutions, as well as the development, scientific substantiation and implementation of the latest nephroprotective detoxification solutions, remain an urgent problem for combustiologists. The aim of this work is to compare the effects of various detoxification solutions (0.9 % NaCl solution and complex colloid-hyperosmolar solutions – lactoprotein with sorbitol and the newly developed HAES-LX-5 % solution) on the kidney structure in experimental burn disease in rats. The experimental rats were divided into seven groups (fifteen animals each): the first group was intact rats; the second, third and fourth groups were rats without reproduction of experimental burn disease, which had a separate intravenous infusion of 0.9 % NaCl solution, lactoprotein with sorbitol and HAES-LX-5 % at a dose of 10 ml/kg; the fifth, sixth and seventh groups were rats with experimental burn disease (by causing burn injury of the skin with an area of 21-23 % of the body surface), which under the same scheme had an intravenous infusion of the investigated solutions. All studies and the removal of rats from the experiment were performed under deep thiopental intraperitoneal anesthesia. Histological preparations of the renal cortex of the rat were stained with hematoxylin-eosin and examined on an Olympus BX51 microscope. Using ultramicrotome LKB-3 (Sweden) obtained semi-thin sections which were stained with toluidine blue and methylene blue – Azur II; and ultrathin sections were counterstained with uranyl acetate and lead citrate according to Reynolds and examined using a PEM-125K electron microscope. Morphometric measurements (estimation of the area of the vascular glomeruli, the area of the urinary lumen of the capsule of the renal corpuscles; the area of the renal tubules of the nephrons and the area of their lumens, the area of the renal corpuscles, the area of cytoplasm and nuclei of epithelial cells of tubules, and also their nuclear-cytoplasmic ratio) was carried out using the VideoTest-5.0, KAARA Image Base and Microsoft Excel on a personal computer. Statistical analysis of the obtained quantitative indicators was performed using the ІВМ SPSS v. 22.0. for Windows. Functionally different cells of nephrons have been found to die by necrosis, apoptosis and anoikis when infused with detoxification solutions during the development of burn disease; in epithelial cells of nephron tubules, mitophagy and mitoptosis occur. Mitoptosis in epithelial cells of rat tubules of nephrons with experimental burn skin injury is carried out in two ways related to: 1) destruction of the outer mitochondrial membrane; 2) preservation of the outer mitochondrial membrane and involvement of autophagic (mitophagic) mechanisms to release the cell from degraded mitochondrial material. In the first case, the mitochondria first condense, after which its matrix swells and the fragmentation of the cristae occurs due to the destruction of the junction of the cristae. Finally, the outer mitochondrial membrane breaks and the remnants of the cristae (in the form of vesicles) go into the cytoplasm. In the second case, the mitochondria condense, vesicular fragmentation of the cristae occurs, but the rupture of the outer mitochondrial membrane does not occur and the mitochondria are absorbed by the autophagosome (or transformed into the autophagosome). Next is the merger of autophagosomes with lysosomes and the formation of autophagolysosomes, which, under the conditions of effective digestion of the contents, are transformed into vacuoles. The latter are emptied by exocytosis and ensure the release of cells from degraded material. Only lactoprotein with sorbitol has a membrane-plastic effect on the strengthening (enhancement of structuring) of the mitochondrial membrane in part of the mitochondria of epithelial cells of nephron tubules, which is ultrastructurally manifested by an increase in the electron density and thickness of all components of the mitochondria. The maximum membrane effect of lactoprotein with sorbitol against mitochondria manifests itself fourteen days after the experimental burn skin injury and gradually (after twenty-one and thirty days) disappears, which is correlated with an improvement in the overall clinical condition and an improvement in the structural changes in the kidney of animals with burn disease. There is every reason to believe that increased structuration of mitochondria is a preventer of the spread of mitoptosis and mitophagy, the excess of which can lead to cell death.
 Bhatia-Kiššová, I., & Camougrand, N. (2010). Mitophagy in yeast: actors and physiological roles. FEMS yeast research, 10(8), 1023-1034. doi: 10.1111/j.1567-1364.2010.00659
 Cherkasov, E. V., Gunas, I. V., Chereshnyuk, I. L., & Lysenko, D. A. (2012). Features of thymus cells cycle in rats after burn lesion of a skin. Ukrainian morphologycal almanac, 2(3), 109-113.
 Davidson, I. J. (2006). Renal impact of fluid management with colloids: a comparative review. European journal of anaesthesiology, 23(9), 721-738. doi: 10.1017/S0265021506000639
 Dzevulska, I. V., Cherkasov, E. V., Kovalchuk, O. I., Majewskyi, Y. G., Pastukhova, V. A., & Kyselova, T. M. (2018). Influence of lactoproteinum solution with sorbitol on DNA content of cells of endocrine glands on the background of skin burn in rats. World of Medicine and Biology, 2(64), 33-39. doi: 10.26724/2079-8334-2018-2-64-33-39
 Gavryluk, A. O., Galunko, G. M., Chereshniuk, I. L., Tikholaz, V. O., Cherkasov, E. V., Dzevulska, І. V., & Kovalchuk, О. І. (2018). Indicators cell cycle and DNA fragmentation in cells of small intestine mucosa 14, 21 and 30 days after skin burns on the background of preliminary infusion of solution lactoprotein with sorbitol or HAES-LX 5%. World of Medicine and Biology, 1(63), 104-108. doi: 10.26724/2079-8334-2017-4-62-104-108
 Groeneveld, A. J., Navickis, R. J., & Wilkes, M. M. (2011). Update on the comparative safety of colloids: a systematic review of clinical studies. Annals of surgery, 253(3), 470-483. doi: 10.1097/SLA.0b013e318202ff00
 Gunas, I. V., Guminskiy, Y. I., Ocheretnа, N. P., Lysenko, D. A., Kovalchuk, О. І., Dzevulska, І. V., & Cherkasov, E. V. (2018). Indicators cell cycle and DNA fragmentation of spleen cells in early terms after thermal burns of skin at the background of introduction 0.9% NaCl solution. World of Medicine and Biology, 14(63), 116-120. doi: 10.26.724/2079-8334-2018-1-63-116-120
 Haagsma, J. A., Graetz, N., Bolliger, I., Naghavi, M., Higashi, H., Mullany, E. C., ... & Ameh, E. A. (2016). The global burden of injury: incidence, mortality, disability-adjusted life years and time trends from the Global Burden of Disease study 2013. Injury prevention, 22(1), 3-18. doi: 10.1136/injuryprev-2015-041616
 Hartog, C. S., Kohl, M., & Reinhart, K. (2011). A systematic review of third-generation hydroxyethyl starch (HES 130/0.4) in resuscitation: safety not adequately addressed. Anesthesia & Analgesia, 112(3), 635-645. doi: 10.1213/ANE.0b013e31820ad607
 Jangamreddy, J. R., & Los, M. J. (2012). Mitoptosis, a novel mitochondrial death mechanism leading predominantly to activation of autophagy. Hepatitis monthly, 12(8), 6159-6163. doi: 10.5812/hepatmon.6159
 Kancir, A. S. P., Johansen, J. K., Ekeloef, N. P., & Pedersen, E. B. (2015). The effect of 6% hydroxyethyl starch 130/0.4 on renal function, arterial blood pressure, and vasoactive hormones during radical prostatectomy: a randomized controlled trial. Anesthesia & Analgesia, 120(3), 608-618. doi: 10.1213/ANE.0000000000000596
 Kaushal, G. P., & Shah, S. V. (2016). Autophagy in acute kidney injury. Kidney international, 89(4), 779-791. doi: 10.1016/j.kint.2015.11.021
 Keck, M., Herndon, D. H., Kamolz, L. P., Frey, M., & Jeschke, M. G. (2009). Pathophysiology of burns. Wiener Medizinische Wochenschrift, 159(13-14), 327-336. doi: 10.1136/bmj.328.7453.1427
 Kovalchuk, O., Cherkasov, E., Dzevulska, I., Kaminsky, R., Korsak, A., & Sokurenko, L. (2017). Dynamics of morphological changes of rats' adenohypophysis in burn disease. Georgian medical news, (270), 104-108. PMID:28972493
 Kruer, R. M., & Ensor, C. R. (2012). Colloids in the intensive care unit. American Journal of Health-System Pharmacy, 69(19), 1635-1642.
 Lakhtadyr, T. V. (2019). Structural changes of the rat kidney cortical substance in the long-term period after burn injury of the skin under conditions of HAES-LX-5% infusion. Emergency Medicine, (5.100), 79-83. https://doi.org/10.22141/2224-05126.96.36.1999.177023
 Lachtadyr, T. V. (2017). Structural changes of rats’ renal cortex in late period of skin burn injury under the conditions of the infusion by lactoprotein with sorbitol. Biomedical and Biosocial Anthropology, 28, 81-87.
 Lyamzaev, K. G., Nepryakhina, O. K., Saprunova, V. B., Bakeeva, L. E., Pletjushkina, O. Y., Chernyak, B. V., & Skulachev, V. P. (2008). Novel mechanism of elimination of malfunctioning mitochondria (mitoptosis): formation of mitoptotic bodies and extrusion of mitochondrial material from the cell. Biochimica et biophysica acta (BBA)-Bioenergetics, 1777(7-8), 817-825. doi: 10.1016/j.bbabio.2008.03.027
 Mijaljica, D., Prescott, M., & Devenish, R. J. (2010). Mitophagy and mitoptosis in disease processes. In Protein Misfolding and Cellular Stress in Disease and Aging (pp. 93-106). Humana Press, Totowa, NJ. doi: 10.1007/978-1-60761-756-3_6
 Mohanan, M., Rajan, S., Kesavan, R., Mohamed, Z. U., Ramaiyar, S. K., & Kumar, L. (2019). Evaluation of renal function with administration of 6% hydroxyethyl starch and 4% gelatin in major abdominal surgeries: A pilot study. Anesthesia, essays and researches, 13(2), 219-224. doi: 10.4103/aer.AER_25_
 Müller, M., & Reichert, A. S. (2011). Mitophagy, mitochondrial dynamics and the general stress response in yeast. Biochem. Soc. Trans., 39(5), 1514-1519. doi: 10.1042/BST0391514
 Mutter, T. C., Ruth, C. A., & Dart, A. B. (2013). Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidney function. Cochrane Database of Systematic Reviews, (7), CD007594. doi: 10.1002/14651858.CD007594.pub3
 Pickles, S., Vigié, P., & Youle, R. J. (2018). Mitophagy and quality control mechanisms in mitochondrial maintenance. Current Biology, 28(4), R170-R185. doi: 10.1016/j.cub.2018.01.004
 Serghiou, M. A., Niszczak, J., Parry, I., Li-Tsang, C. W. P., Van den Kerckhove, E., Smailes, S., & Edgar, D. (2016). One world one burn rehabilitation standard. Burns, 42(5), 1047-1058. doi: 10.1016/j.burns.2016.04.002
 Smolle, C., Cambiaso-Daniel, J., Forbes, A. A., Wurzer, P., Hundeshagen, G., Branski, L. K., ... & Kamolz, L. P. (2017). Recent trends in burn epidemiology worldwide: A systematic review. Burns, 43(2), 249-257. doi: 10.1016/j.burns.2016.08.013
 Tinari, A., Garofalo, T., Sorice, M., Esposti, M. D., & Malorni, W. (2007). Mitoptosis: different pathways for mitochondrial execution. Autophagy, 3(3), 282-284. doi: 10.4161/auto.3924
 Vigie, P., & Camougrand, N. (2017). Role of mitophagy in the mitochondrial quality control. Medecine sciences: M/S, 33(3), 231-237. doi: 10.1051/medsci/20173303008
 Weiskopf, R. B. (2015). Lack of Nephrotoxicity of Hydroxyethyl Starch 130/0.4 When Used in Surgery. The Journal of the American Society of Anesthesiologists, 123(2), 482-483. doi: 10.1097/ALN.0000000000000719
 Zemirli, N., Morel, E., & Molino, D. (2018). Mitochondrial dynamics in basal and stressful conditions. International journal of molecular sciences, 19(2), 564. doi: 10.3390/ijms19020564
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