THE EFFECT OF NEW PLANT HEPATOPROTECTORS ON THE LEVEL OF PROINFLAMMATORY CYTOKINES IN ACUTE TOXIC LIVER DAMAGE
DOI:
https://doi.org/10.61841/vdhc6655Keywords:
acute hepatitis, heliotrin, pharmacotherapy, carsil, geranyl, catacin, kavergal, pro-inflammatory cytokines.Abstract
Purpose of the research: a comparative study of the molecular mechanisms of the anti-inflammatory action of catacin, geranium, cavergal in comparison with carlsil in a model of acute toxic liver damage with heliotrin. Material and methods. Studies were carried out on 118 adult male rats. The model of acute toxic damage (ATD) was reproduced by a single subcutaneous injection of heliotrin at a dose of 200 mg / kg of animal body weight in 110 rats, 8 rats made up the intact group. On the 3rd day of the toxicant administration, the surviving animals were divided into 5 groups: 1) ATD + physiological saline at a dose of 0.5 ml / 100 g body weight (control) of 20 rats; 2) ATD + carsil (comparison group) 19 rats; 3) ATD + catacin 19 rats; 4) ATD + geranyl of 19 rats; 5) ATD + cover 18 rats. The drugs were administered intragastrically daily in the morning at 100 mg / kg for 6 and 12 days. 24 hours after the final administration of the plant preparations, the animals were killed under mild anesthesia. The development of toxic hepatitis was judged by the activity of ALT and AST, the content of bilirubin and its fractions in serum using a MINDRAYBA-88A biochemical analyzer (China) using commercial reagent kits from CYPRESS Diagnostics (Belgium). The content of IL-1β, IL-6 and TNF-α was determined by enzyme-linked immunosorbent assay on an ELYZA apparatus (Germany) using Bender Medsystems kits. For statistical processing of the results, Exell and OriginPro7.5 software packages (OriginLab Corporation, USA) were used. Results. The results of the study showed a sharp increase in the level of pro-inflammatory cytokines in ATD rats, especially those responsible for the humoral immunity. Experimental pharmacotherapy with new drugs from the group of flavonoids and proanthacyanidins leads to a decrease in the production of proinflammatory cytokines, and catacin and geranyl preparations turned out to be more effective in this regard. Conclusion: the studied new herbal preparations catacin and geranyl in rats with ATD significantly suppressed the high level of pro-inflammatory cytokines, which may indicate their anti-inflammatory activity.
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References
1. Abdullaev G. R. Influence of catacin on rat lipid peroxidation processes in the dynamics of stress development // Uzbek Biological Journal. 2016. - No. 3. - P. 7-11;
2. Azarova OV, Galaktionova L.P. Flavonoids: a mechanism of anti-inflammatory action // Chemistry of plant materials. - 2012.- No. 4.- P. 61-78.
3. Almatov K. T., Abdullaev G. R. Changes in the energy metabolism of rat liver mitochondria in the dynamics of the development of chronic emotional and pain stress and their correction with catacin // Uzbek Biological Journal. 2016. - No. 2. - P. 20-26.
4. Alyavi A.L., Kochovskaya I.V., Komarin A.S. Clinical efficacy of cavergal in the complex treatment of patients with chronic pyelonephritis (methodological recommendations).- Tashkent, P. 2008.- 24.
5. Zverev Y. F. Flavonoids through the eyes of a pharmacologist. Antioxidant and anti-inflammatory activity
// Reviews on clinical pharmacology and drug therapy. - 2017.- T.15, No. 4.- P.5-15.
6. Zenkov N.K., Menshchikova E.B., Tkachev V.O. The redox-sensitive Keap1/Nrf2/ARE signaling system as a pharmacological target. Overview // Biochemistry. - 2013. - T. 78. - No. 1. - P. 27–47;
7. Inoyatova F.Kh., Rakhmanov A.Kh., Kurbanova NN, Aslanova A.Kh. Influence of new hepatoprotectors on the detoxifying function of rat liver during its acute toxic damage // Vestnik TMA.- 2018.- No. 3. - P. 70-74.
8. Israilov R.I., Kurbanova N.N., Khushbaktova Z. A. Influence of herbal preparations on the morphology of the liver in case of its acute toxic damage // Vestnik NU.- 2019.- No. 2. – P.46-50.
9. Korotchaeva Yu.V., Samokhodskaya L.M., Speransky A.I., Kozlovskaya L.V. The prognostic value of the determination of IL-6 in serum and cytochrome P450 in the liver tissue in patients with chronic hepatitis C.
// Journal of Gastroenterology, Hepatology and Coloproctology.- 2008.- No. 2.- P.42-47
10. Mammaev S.N., Ramazanov Sh.R., Bueverov A.O. et al. Dynamics of serum cytokine levels during antiviral therapy of chronic hepatitis C. // Wedge of the prospect of gastroenterology, hepatology.-2008-No. 2.-P. 28-31.
11. Nazrullaev A.M., Mirzaahmedov B.M. The study of chronic toxicity of the drug katatsin // Uzbek Biological Journal. - 2016. - No. 2. - P. 26-29.
12. Novikov V.N., Klimkina E.I. Pharmacology of hepatoprotectors // Reviews of clinical pharmacology and drug therapy.- 2005.- T.4, No. 1.- P.2-20.
13. Norbutaeva D.A., Syrov V.V., Khushbaktova Z.A. Evaluation of the antihypoxic and antioxidant properties of proanthocyanidins from rock geranium // Science and Innovation of the 21st Century. Materials of the first All-Russian Conference of Young Scientists".- Surgut, 2012.- P.138-142.
14. Norbutaeva D.A., Siddikov D.R., Nishanbaev S.Z., Syrov V.V., Khushbaktova Z.A. Antihypoxic properties of proanthocyanidins from some plants of Uzbekistan // DAN RUz.- 2011.- No. 5.- P.58-60.
15. Siddikov D.R. Nishanbaev S.Z., Norbutaeva D.A., Babakulov H.M. Secondary metabolites of the aerial part of Geranimumsaxatile // Chemistry of natural compounds.- 2013.- No. 2.- P.289-290.
16. Tarakhovsky Yu.S., Kim Yu.A., Abdrasilov B.S., Muzaffarov E.N. Flavonoids: biochemistry, biophysics, medicine. - Pushchino: Synchrobook, 2013.,
17. Ushkalova E.A. Problems of using hepatoprotectors // Farmateka. - 2004. - No. 4. - P. 45-55.
18. Cytokines. // www.biochemmack.ru.- 2014.- P.401-421.
19. Agati G., Azzarello E., Pollastri S., Tattini M. Flavonoids as antioxidants in plants: location and functional significance // Plant Science. - 2012. - Vol. 196. – P. 67–76.;
20. Antonio Ayala, Mario F. Muñoz, Sandro Argüelles. Lipid Peroxidation: Production, Metabolism Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal // Oxidative Medicine and Cellular Longevity.- 2014.- Vol. Article ID 360438, 31 pages, doi.org/10.1155/2014/360438.
21. Birrell M.A., McCluskie K., Wong S.S., Donnelly L.E., Barnes P.J., Belvisi M.G. Resveratrol, an extract of red wine, inhibits lipopolysaccharide induced airway neutrophilia and inflammarory mediators through an NF-kppaB-independent mechanism //FASEB J.- 2005.- Vol.19.- P.840-841.
22. Friedman S. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury // J. Biol. Chem. – 2000. – Vol. 275 (4). – P. 2247–2250.
23. Karimov Kh.Ya., Inoyatova F.H., Karabanovich A.K. Correction of disorder of the liver microcirculation and functionally metabolic parameters of rats with acute toxic hepatitis // The International Toxicologist Abstracts of the International Congress of Toxicology-YII, 1995 Seattle, Waschington. USA, 7. - P.13.
24. Kim H.P., Son K.H., Chang H.W., Kang S.S. Anti-inflammatory plant flavonoids and cellular action mechanisms // Journal of Pharmacological Sciences.- 2004.- Vol.96.- P.229-245.
25. Lago JHG, Toledo-Arruda AC, Mernak M, et al. Struc-ture-activity association of flavonoids in lung diseases. Molecules. 2014;19(3):3570-95. DOI: 10.3390/mole-cules19033570.
26. Mathurin P., Bataller R.(2015). Trends in the management and burden of alcoholic liver disease. J. Hepatology, 62, P.38-46.
27. Nitesh Kumar, Amita Rai, Neetinkumar D. Reddy, Rekha R. Shenoy, Jayesh Mudgal et al. Improved in vitro and in vivo hepatoprotective effects of liposomal silymarin in alcohol-induced hepatotoxicity in Wistar rats. Pharmacological Reports 71 (2019)703-712, www.elsevier.com/locate/pharep.
28. Rauf Abdur., Muhammad Imran., Tareq Abu-Izneid., Iahtisham-Ul-Haq., Seema Patel., Xiandao Pan., Saima Naz., Ana Sanches Silva., Farhan Saeed.,Hafiz Ansar Rasul Suleria. (2019). Proanthocyanidins: A comprehensive review. Biomedicine & Pharmacotherapy, 116, 188999. www.elsevier.com/locate/biopha
29. Satsu H., Hyun J.S., Shin H.S., Shimizu M. Suppressive effect of an izoflavone fraction on tumor necrosis factor-alpha-induced interleukin-8 production in human intestinal epithelial Caco-2 cells //Journal of Nutritional Science and Vitaminology.- 2009.- Vol.55, N5.- P. 442-446.
30. Shashank Kumar, Abhay K. Pandey.Chemistry and Biological Activities of Flavonoids: An Overview (Review Article) // The Scientific World Journal Vol.- 2013, Article ID 162750, 16 p. doi.org/10.1155/2013/162750.
31. Shih PH, Yeh CT, Yen GC. Anthocynins induce activation of phase II enzymes through the antioxidant response ele-ment pathway against oxidative stress-induced apoptosis. //J Agric Food Chem. 2007;55(23): 9427-35.
32. Suganthy N., Devi.KP, Nabavi.SF, Braidy.N, Nabavi SM. Bioaktive effects of querciten in the central nervous system: Focusing on the mechanisms of actions // Biomedicine Pharmacotherapy 84, 892-908, 2016
33. Szelag A, Magdalan J, Kopacz M, et al. Assessment of efficacy of quercetin-5’- sulfonic acid sodium salt in the treatment of acute chromium poisoning: Experimental studies. // Pol J Pharmacol. 2003;55(6): 1097-1103.
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