PATHOGENETIC SUBSTANTIATION OF APPLICATION OF ANTRAL IN PATIENTS WITH COMORBIDAL COURSE OF NON-ALCOHOLIC STEATHEPATITIS, OBESITY AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE – INFLUENCE ON CONNECTIVE TISSUE COMPONENTS AND BLOOD CONTENT OF HYDROGEN SULFIDE

Khukhlina O. S., Hryniuk O. Ye., Roshchuk O. I., Liakhovych O. D.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Abstract. The work evaluates the effectiveness of Antral and its effect on fibrotic processes in the liver and lungs. The study included 60 patients with non-alcoholic steatohepatitis (NASH), obesity of I degree and chronic obstructive pulmonary disease (COPD) 2-3B, D, of which 32 patients with COPD 2B (group 1) and 28 patients (group 2) COPD 3D received COPD therapy (Symbicort Turbuhaler (budesonide 160 mg/d + formoterol fumarate 4,5 mg/d) (AstraZeneca AB, Sweden) inhaled 2 times per day for 60 days, Berodual (ipratropium/fenoterol (250/500 mg/ ml) (Institute de Angele Italy / Boehringer Ingelheim International GmbH) nebulizer inhalation 2 times per day, azithromycin (Azithro Sandoz, Ukraine Sandoz) 500 mg, 1 time per day for 10 days) and also they received Antral (Farmak, Ukraine) 200 mg, 3 times per day for 60 days as a hepatoprotector. It was found that in NASH patients with comorbid COPD, which arose against the background of obesity, significantly increased collagen synthesis, respectively, in patients of the 1st and 2nd groups in 2,6 and 3,4 times in comparison with the group of apparently healthy persons (AHP) (p<0,05). These processes were accompanied by a deficiency of hydrogen sulfide, respectively, in 1,5 and 2,8 times (p<0,05) compared with the index in the AHP. Antral, when administered as a course for 60 days to NASH patients against the background of obesity with comorbid COPD, probably inhibits the synthesis of type IV collagen and carbohydrate-protein components of the extracellular matrix of the liver and lungs, probably enhances their degradation and helps restore the pool of hydrogen sulfide in blood. Complex therapy of using Antral helps to inhibit liver fibrosis with a probable decrease in the integral FibroTest indicator by 1,2 times (p<0,05).

non-alcoholic steatohepatitis, obesity, chronic obstructive pulmonary disease, fibrosis, antral.

1. Khukhlina OS, Antoniv AA, Mandryk OYe, Hryniuk OYe. Nealkoholna zhyrova khvoroba pechinky ta komorbidni stany: osoblyvosti patohenezu, kliniky, diahnostyky, likuvannia. Chernivtsi; 2017. 188 s. [in Ukrainian].
2. Viglino D, Jullian-Desayes I, Minoves M, Aron-Wisnewsky J, Leroy V, Zarski JP, et al. Nonalcoholic fatty liver disease in chronic obstructive pulmonary disease. Eur Respir Jour. 2017 Jun 8;49(6):1601923. DOI: 10.1183/13993003.01923-2016.
3. Alukal JJ, Thuluvath PJ. Reversal of NASH fibrosis with pharmacotherapy. Hepatol Int. 2019;13(5):534-545. DOI: 10.1007/s12072-019- 09970-3.
4. Weiskirchen R. Cellular and Molecular Mechanisms Underlying the Pathogenesis of Hepatic Fibrosis. Cells. 2020 Apr 29;9(5):1105. DOI: 10.3390/cells9051105.
5. Diadyk OO, Beketova YuI, Mintser OP, Sukhanova OO. Suchasni patomorfolohichni osoblyvosti ta perspektyvni napriamky diahnostyky nealkoholnoho steatohepatytu. Art of medicine. 2018;3(7):39-44. [in Ukrainian].
6. Chakraborty JB, Oakley F, Walsh MJ. Mechanisms and biomarkers of apoptosis in liver disease and fibrosis. Int. J. Hepatol. 2012;2012:648- 915. DOI: 10.1155/2012/648915.
7. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease 2019 report [Internet]. 2019 [updated 2019 March 22]. Available from: https://goldcopd.org/wp-content/ uploads/2018/11/GOLD-2019-v1.7-FINAL-14Nov2018-WMS.pdf.
8. Vanfeteren LE, Spruit MA, Wouters EFM, Franssen FME. Management of chronic obstructive pulmonary disease beyond the lungs. Lancet Respir. Med. 2016;4:911-924.
9. Vanfleteren LE. Does COPD stand for “Comorbidity with Pulmonary Disease”? Eur Respir J. 2015;45:14-17.
10. Koike S, Ogasawara Y. Sulfur atom in its bound state is a unique element involved in physiological functions in mammals. Molecules. 2016;21(12):17-53.
11. Fan HN, Chen NW, Shen WL, Zhao XY, Zhanget Z. Endogenous hydrogen sulfide is associated with angiotensin II type 1 receptor in a rat model of carbon tetrachloride-induced hepatic fibrosis. Molecular Medicine Reports. 2015;12(3):3351-3358. DOI: 10.3892/mmr.2015.3873
12. Nekrut DO, Zaichko NV, Strutynska OB. Riven insulinopodibnogo faktoru rostu-1 ta gidrogensulfidu u shhuriv iznealkogolnoyu zhyrovoyu xvoroboyu pechinky, asocijovanoyu iz gipergomocysteyinemiyeyu. Medychna ta klinichna ximiya. 2017;19(1):40-46. [in Ukrainian].
13. Gerush IV, Ferenchuk OYe. Hydrogen sulfide and mitochondria. Biopolymers and Cell. 2019;35(1):3-15.
14. Kabil O, Motl N, Banerjee R. H2S and its role in redox signaling. Biochimica et Biophysica Acta. 2014;1844(8):1355-1366.
15. Yuan S, Pardue S, Shen X, Alexander JS, Orr AW, Kevil CG. Hydrogen sulfide metabolism regulates endothelial solute barrier function. Redox Biol. 2016;9:157-166. DOI: 10.1016/j.redox.2016.08.004.
16. Bazhanov N, Ansar M, Ivanciuc T, Garofalo R, Casola A. Hydrogen sulfide: a novel player in airway development, pathophysiology of respiratory diseases, and antiviral defenses. Am J Respir Cell Mol Biol. 2017;57:403- 10.
17. Anokhina AA. Nealkoholna zhyrova khvoroba pechinky yak multysystemne metabolitne zakhvoriuvannia: osoblyvosti profilaktyky ta likuvannia. Hepatolohiia. 2018;7(3):35-40. [in Ukrainian].
18. Zvjaginceva TD. Primenenie preparata Antral’ v lechenii nealkogol’nogo steatogepatita: nastojashhee i budushhee. Zdorov`ya Ukrayiny XXI storіchchja. 2015;1(2):68-69.[in Russian].
19. Khukhlina OS, Dudka IV, Dudka TV, Smandych VS, Pavliuk VO. Vplyv tsytoprotektora Antral na oksydantno-antyoksydantnyi homeostaz u khvorykh na khronichnyi pankreatyt. Zdorov`ya Ukrayiny. 2020;16(485):59-60. [in Ukrainian].
20. Khukhlina OS, Dudka IV, Dudka TV, Smandych VS. Klinichna efektyvnist preparatu Antral u khvorykh na khronichnyi pankreatyt. Zdorov`ya Ukrayiny. 2020;3(57):17. [in Ukrainian].
21. Derbak MA, Arkhii EI, Koval VIu, Derbak YaS. Vykorystannia antraliu u kompleksnii terapii khvorykh na khronichnyi virusnyi hepatyt iz suputnim steatozom pechinky. Naukovyi visnyk Uzhhorodskoho universytetu. 2011;2(41):304-30. [in Ukrainian].
22. Khukhlina OS, Hryniuk OYe, Antoniv AA. Intensyvnistʹ oksydatyvnoho stresu ta stan okremykh chynnykiv antyoksydantnoho zakhystu v dynamitsi likuvannya antralem khvorykh na nealkoholʹnyy stetohepatyt, ozhyrinnya ta khronichne obstruktyvne zakhvoryuvannya lehenʹ. EUMJ. 2020;8(2):129-136. DOI: https://doi.org/10.21272/eumj. 2020;8(2):129-136. [in Ukrainian].
23. Khukhlina OS, Hryniuk, Antoniv AA. Treatment optimization of non-alcoholic steatohepatitis in obesity patients with comorbidity with chronic obstructive pulmonary disease: correction of dyslipidemia and insulin resistance. Contemporary gastroenterology. 2020;1(71):105-113.

«Bulletin of problems biology and medicine» Issue 2 (160), 2021 year, 148-152 pages, index UDK 616.36-003.826:616-056.527:616.24-007.272]-036.1-07-092-085.244

10.29254/2077-4214-2021-2-160-148-152