online ISSN 2415-3176
print ISSN 1609-6371
logoЕкспериментальна та клінічна фізіологія і біохімія
Ж. 2023, 96(1): 12–17
https://doi.org/10.25040/ecpb2023.01-02.012

Експериментальна медицина


Metabolic changes in the extracellular matrix of rat liver under the conditions of chronic alcoholic hepatitis modeling

A. O. Mykytenko
Анотація

Summary.
The pathogenesis of chronic alcoholic hepatitis is multifactorial. Despite decades of research, there is still a clinical void in the highly effective treatment of alcoholic hepatitis, therefore the search for pathogenetic means of therapy should be directed at establishing new links in the pathogenesis of chronic alcoholic hepatitis. The purpose of this work was to study the biochemical markers of the metabolism of the extracellular matrix (ECM) of rat liver under the conditions of chronic alcoholic hepatitis modeling.
Methods: experiments were performed on 30 white male Wistar rats, weighing 180-220 g. The animals were divided into 2 groups: І – control (n=6); ІІ group – chronic alcoholic hepatitis (n=24) group modelled by the method of forced intermittent alcoholization. Animals were removed from the experiment on days 35, 42, 49 and 56 by bloodletting under thiopental anesthesia.
In the homogenate of rat liver, the total concentration of glycosaminoglycans and their fractions (heparin-heparan, keratan-dermatan and chondroitin), the concentration of free oxyproline and sialic acids were determined.
Results: We found that the proteoglycans of the liver ECM undergo the greatest depolymerization on the 35th day. On the 56th day of the experiment, the total concentration of glycosaminoglycans decreased below control values due to a decrease in the concentration of the heparin-heparan fraction of glycosaminoglycans against the background of an increase in the content of chondroitin and keratan-dermatan fractions of glycosaminoglycans. The highest intensity of collagenolysis was observed on the 42nd day, as evidenced by the highest content of free oxyproline in the liver. Glycoproteins underwent the greatest catabolism on the 56th day, which was evidenced by an increase in sialic acids.
Conclusion: Under the conditions of chronic alcoholic hepatitis development, there is a violation of remodeling of the extracellular matrix of the liver, which is accompanied by increased collagenolysis and desialylation of glycoproteins.

Article received: 14.03.2023

Ключові слова: alcoholic hepatitis, glycosaminoglycans, sialic acids, oxyproline, heparin, dermatan sulfate, chondroitin sulfate

Повний текст: PDF (Ukr)

Список літератури
  1. 1. Sehrawat TS, Liu M, Shah VH. The knowns and unknowns of treatment for alcoholic hepatitis. Lancet Gastroenterol Hepatol. 2020 May;5 (5): 494-506. doi.org/10.1016/S2468-1253(19)30326-7
  2. 2. Clemente-Sánchez A, Oliveira-Mello A, Bataller R. Moderate Alcoholic Hepatitis. Clin Liver Dis. 2021 Aug; 25 (3): 537-555.doi.org/10.1016/j.cld.2021.03.001
  3. 3. Hosseini N, Shor J, Szabo G. Alcoholic Hepatitis: A Review. Alcohol Alcohol. 2019 Jul 1;54(4):408-416. doi.org/10.1093/alcalc/agz036
  4. 4. Hyun J, Han J, Lee C, Yoon M, Jung Y. Pathophysiological Aspects of Alcohol Metabolism in the Liver. Int J Mol Sci. 2021 May 27; 22 (11): 5717.doi.org/10.3390/ijms22115717
  5. 5. Liu M, Xu y, Han X, yin L, Xu L, Qi y, Zhao y, Liu k, Peng J. Dioscin alleviates alcoholic liver fibrosis by attenuating hepatic stellate cell activation via the TLR4/MyD88/NF-κB signaling pathway. Sci Rep. 2015 Dec 10;5:18038.doi.org/10.1038/srep18038
  6. 6. Rachakonda V, Bataller R, Duarte-Rojo A. Recent advances in alcoholic hepatitis.F1000Res. 2020 Feb 10;9:F1000 Faculty Rev-97.doi.org/10.12688/f1000research.20394.1
  7. 7. Stepanov YuM, Didenko VI, Dynnik OB, Konenko IS, Oshmianskaia NYu, Galinsky AA. Association of morphological changes in the liver parenchyma and its rigidity under the conditions of the experimental modeling of alcoholic and toxic hepatitis. Journal of the NAMSU. 2017; 23 (3-4): 196-204.
  8. 8. Mykytenko A.O., Akimov O.ye., yeroshenko G.A., neporada k.S. Influence of transcription factor κb on remodeling of extracellular matrix of rat liver under conditions of chronic alcohol intoxication. World of Medicine and Biology. 2022; 80(2): 214-217.doi.org/10.26724/2079-8334-2022-2-80-214-217
  9. 9. Nadanaka S, Hashiguchi t, kitagawa H. Aberrant glycosaminoglycan biosynthesis by tumor suppressor EXTL2 deficiency promotes liver inflammation and tumorigenesis through Toll-like 4 receptor signaling. FASEB J. 2020 Jun;34(6):8385-8401.doi.org/10.1096/fj.201902076R
  10. 10. Mormone E, George J, nieto n. Molecular pathogenesis of hepatic fibrosis and current therapeutic approaches. Chem Biol Interact. 2011 Sep 30;193(3):225-31.doi.org/10.1016/j.cbi.2011.07.001
  11. 11. Chrostek L, Cylwik B, Panasiuk A, Brodowska-Adamusiak D, Gruszewska E. Lipid-bound sialic acid (LSA) in liver diseases of different etiologies. Ann Hepatol. 2011 Apr-Jun;10(2):150-4.doi.org/10.1016/S1665-2681(19)31563-7
  12. 12. McVicker BL, thiele GM, tuma DJ, Casey CA. Hepatocyte-mediated cytotoxicity and host defense mechanisms in the alcohol-injured liver. Hepatol Int. 2014 Sep;8 Suppl 2:432-8.doi.org/10.1007/s12072-013-9511-7
  13. 13. Chrostek L, Cylwik B. Zaburzenia glikozylacji białek w chorobach watroby [The alteration of proteins glycosylation in liver diseases]. Pol Merkur Lekarski. 2011 Jul;31(181):60-4. [Polish].
  14. 14. Blomme B, Van Steenkiste C, Callewaert n, Van Vlierberghe H. Alteration of protein glycosylation in liver diseases. J Hepatol. 2009 Mar;50(3):592-603.doi.org/10.1016/j.jhep.2008.12.010


Програмування - Roman.im | QR-Code Generator