Changes of the oxidant-antioxidant homeostasis and some cytokines in patients with blastomatous jaundice of various severity
Objective. Investigation of state of a free-radical processes, peroxidal oxidation of lipids, аntiradical defense and content of cytokines in the blood serum in patients, suffering blastomatous jaundice.
Маterials and methods. The investigation was conducted in 80 patients, ageing 38- 83 yrs old, who have had blastomatous jaundice preoperatively. All the patients were distributed into three Groups, depending on classification of Е. І. Galperin (2012), for estimation and prognosis of postoperative results. Into the 1-st Group were included 18 (22.5%) patients with jaundice Class А, to the 2-nd Group - 32 (40%) patients with jaundice Class В, and tо the 3-d Group - 30 (37.5%) patients with jaundice Class С. In 68 (85%) patients the Stages III and IV of the disease were diagnosed.
Results. In environment of clinical course of the blastomatous jaundice of all three Classes of severity the content of the middle-molecules peptides and аmmonia in the blood serum of the patients have been enhanced significantly; аntioxidant homeostasis was characterized by enhancement of content of malonic dialdehyde in the blood serum, dienic conjugates, raising activity of cerulloplasmin and lowering - of catalase (р < 0.05); the content of cytokines IL-1β, IL-6 and ІL-8 in the blood serum have been heightened (р < 0.05), while a dynamics of the cytokines ІL-4 and ІL-10 content changes was an adverse one (р < 0.05). Comparison of the median value of the intergroup differences in accordance to Spearman criterion have shown, that the indices of the VEGF level were trustworthily probable in patients, suffering jaundice of Classes A and B (r = -0.90, p = 0.000), of Classes B and C (r = 0.726, p = 0.000), and Classes A and C (r = 0.489, p = 0.041). There was established, that the VEGF level, median value of which have constituted 346 pg/ml, was the only one index, which have had more accuracy, comparing with patients, suffering cancer, or with conditionally healthy persons (the square under the RОС-curve have constituted 0.943, sensitivity - 86.8%, specificity - 82.4%, general accuracy - 82.3%).
Conclusion. Functional disorders of endothelial cells and of a vascular smooth muscle cells, іnduced by a free-radical processes and the antiradical defense system, leads to development of endothelial and vascular dysfunction, which, possibly, іnitiates and induces a vascular hypoactivity and vasodilation, the level of VEGF has more accuracy, comparing with patients, suffering cancer and the conditionally healthy persons.
2. Green J, Better OS. Systemic hypotension and renal failure in obstructive jaundice-mechanistic and therapeutic aspects. J Am Soc Nephrol. 1995 May;5(11):1853-71. PMID: 7620083.
3. Kimmoun A, Ducrocq N, Levy B. Mechanisms of vascular hyporesponsiveness in septic shock. Curr Vasc Pharmacol. 2013 Mar 1;11(2):139-49. PMID: 23506493.
4. Chan A, Diamandis EP, Blasutig IM. Strategies for discovering novel pancreatic cancer biomarkers. J Proteomics. 2013 Apr;81:126-34. doi: 10.1016/j.jprot.2012.09.025.
5. Galperin EI, Momunova ON. Klassifikatsiya tyazhesti mehanicheskoy zheltuhi. Hirurgiya. 2014;(1):5-9. [In Russian].
6. Galperin EI. Klassifikatsiya tyazhesti mehanicheskoy zheltuhi. Annalyi hir gepatol. 2012;(2):26-34. [In Russian].
7. Fedorova TK. Reaktsiya s tiobarbiturovoy kislotoy dlya opredeleniya malonovogo dialdegida v krovi metodom flyuorimetrii. Lab. delo. 1983;(3):25-8 [In Russian].
8. Kosuhin AB. Ekstraktsiya lipidov smesyu geptan-izoprapanol dlya opredeleniya dienovyih konyugatov. Lab Delo. 1987;(5):335-7 [In Russian].
9. Dubinina EE. Metodyi opredelenie aktivnosti katalazyi. Lab delo. 1988;8:16-9. [In Russian].
10. Moshkov KA. Opredelenie fermentativnoy aktivnosti i immunoreaktivnosti tseruloplazmina v syivorotke krovi cheloveka. Lab delo. 1985;(7):390-5 [In Russian].
11. Archakov AI. Okislenie chuzherodnyih soedineniy. Vestnik AMN SSSR. 1988;(1):14-23 [In Russian].
12. Copple BL, Jaeschke H, Klaassen CD. Oxidative stress and the pathogenesis of cholestasis. Seminars in Liver Disease. 2010 May;30(2):195-204. doi: 10.1055/s-0030-1253228.
13. Yung LM, Leung FP, Yao X, Chen Z-Y, Huang Y. Reactive oxygen species in vascular wall. Cardiovascular and Hematological Disorders-Drug Targets. 2006 March; 6(1):1-19. doi: 10.2174/187152906776092659.
14. Barón V, Muriel P. Role of glutathione, lipid peroxidation and antioxidants on acute bile duct obstruction in the rat. Biochim Biophys Acta. 1999 Oct 18;1472(1-2):173-80. doi: 10.1016/s0304-4165(99)00118-x.
15. Galicia-Moreno M, Favari L, Muriel P. Antifibrotic and antioxidant effects of N-acetylcysteine in an experimental cholestatic model. Eur J Gastroenterol Hepatol. 2012 Feb; 24(2): 179-85. doi: 10.1097/MEG.0b013e32834f3123.
16. Capone F, Guerriero E, Sorice A, Colonna G, Ciliberto G, Costantini S. Serum Cytokinome Profile Evaluation: A Tool to Define New Diagnostic and Prognostic Markers of Cancer Using Multiplexed Bead-Based Immunoassays. Mediators Inflamm. [Internet]. 2016;2016:3064643. Available from: https://www.hindawi.com/journals/mi/2016/3064643/. doi: 10.1155/2016/3064643.
17. Katz, SC, Ryan, K, Ahmed N, Plitas G, Chaudhry, UI, Kingham TP, et al. Obstructive jaundice expands intrahepatic regulatory T cells, which impair liver T lymphocyte function but modulate liver cholestasis and fibrosis. J Immunol. 2011 Aug 1;187(3):1150-6. doi: 10.4049/jimmunol.1004077.
18. Hu X, Ivashkiv LB. Cross-regulation of signaling pathways by interferon-γ: implications for immune responses and autoimmune diseases. Immunity. 2009 Oct 16;31(4):539-50. doi: 10.1016/j.immuni.2009.09.002.
19. Mlecnik B, Bindea G, Kirilovsky A, Angell HK, Obenauf AC, Tosolini M, et al. The tumor microenvironment and Immunoscore are critical determinants of dissemination to distant metastasis. Science Translational Medicine. 2016 Feb 24; 8(327):327ra26. doi:10.1126/scitranslmed.aad6352.327ra26.
20. Church SE, Galon J. Tumor microenvironment and immunotherapy: the whole picture is better than a glimpse. Immunity. 2015;43(4):631-633. doi: 10.1016/j.immuni.2015.10.004.
21. Elenkov IJ, Iezzoni DG, Daly A, Harris AG, Chrousos GP. Cytokine dysregulation, inflammation and well-being. Neuroimmunomodulation. 2005;12(5):255-69. doi: 10.1159/000087104.
22.Waite JC, Skokos D. Th17 response and inflammatory autoimmune diseases. Int J Inflam. 2012;2012:819467. doi: 10.1155/2012/819467.
23. Costantini S, Capone, Guerriero E, Castello G. An approach for understanding the inflammation and cancer relationship. Immunology Letters. 2009Sept 22;126(1-2):91-2. doi: 10.1016/j.imlet.2009.08.006.
24. Victor WM, van Hinsbergh VWM. Endothelium—role in regulation of coagulation and inflammation. Semin Immunopathol. 2012 Jan;34(1):93-106. doi: 10.1007/s00281-011-0285-5.
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