The aim of the work was the study of the level of Hgf gene mRNA expression in the liver of rats with glutamate-induced steatohepatosis and under the action of the multiprobiotic “Symbiter acidophilic” concentrated (multiprobiotic) and nanocrystalline cerium dioxide (NCD). Material and methods. The experiments were performed on 4 groups of white nonlinear male rats. Rats of the first group served as controls. Animals of the other three groups were injected subcutaneously with sodium L-glutamate (4 mg/kg) for 2, 4, 6, 8 and 10 days. From 1 month of age and for the next three months, rats of the third and fourth groups (after neonatal administration of monosodium glutamate) were periodically orally administered respectively multiprobiotic (0.14 ml/kg) and NDC (1 mg/kg) according to the scheme: 2 weeks of administration, 2 weeks break. In the rats liver of 4 month old we determined the level of expression of mRNA gene Hgf. Results. The level of expression of mRNA gene Hgf in the group of glutamate-induced obese animals was 4.2 times (p<0.001) higher compared to intact rats. In rats after neonatal administration of monosodium glutamate, which was periodically administered the multiprobiotic, this figure returned to control values. In rats after neonatal administration of monosodium glutamate, which were periodically injected with NCD, this figure was 2.8 times (p<0.001) lower than in control animals. Conclusion. Multiprobiotic and NCD significantly reduced the expression of Hgf mRNA expression in rat liver after administration of sodium glutamate in the early neonatal period, indicating a reduction in inflammation and liver fibrosis.

Received: 17.02.2022

Keywords: steatohepatosis, glutamate-induced obesity, gene Hgf, multiprobiotic, nanocrystalline cerium dioxide

Full text: PDF (Ukr) 417K

1. 1. Wоrld Hеаlth Оrgаnіzаtіоn. WHO – Fact sheet – Obesity and overweight. Updated February 201
2. 2. STEPS: prevalence of noncommunicable disease risk factors in Ukraine 2019. Copenhagen: WHO Regional Office for Europe; 2020. Licence: CC BY-NC-SA 3.0 IGO.
3. 3. Willebrords J, Pereira IVA, Maes M, Yanguas SC, Colle I, Bossche BVD, Da silva TC, Oliveira CP, Andraus W, Alves VAF, Cogliati B, Vinken M. Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research. Prog Lipid Res. 2015; 59:106-125.
4. 4. Than NN, Newsome PN. A concise review of non-alcoholic fatty liver disease. Atherosclerosis. 2015; 239(1):192-202.
5. 5. Machado M, Marques-Vidal P, Cortez-Pinto HJ. Hepatol. Hepatic histology in obese patients undergoing bariatric surgery. 2006; 45(4):600-606.
6. 6. Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011; 34(3):274-85.
7. 7. Attar BM, Van Thiel DH. Current Concepts and Management Approaches in Nonalcoholic Fatty Liver Disease. Sci World J. 2013:481893.
8. 8. Gaggini M, Morelli M, Buzzigoli E, DeFronzo RA, Bugianesi E, Gastaldelli A. Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease. Forum Nutr. 2013; 5:1544–60.
9. 9. He X, Ji G, Jia W, Li H. Gut Microbiota and Nonalcoholic Fatty Liver Disease: Insights on Mechanism and Application of Metabolomics. Int J Mol Sci. 2016; 17(3):300.
10. 10. Le Roy T, Llopis M, Lepage P, Bruneau A, Rabot S, Bevilacqua C, Martin P, Philippe C, Walker F, Bado A, Perlemuter G, Cassard-Doucier A-M, Gerard P. Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice. Gut. 2013; 62(12):1787-1794.
11. 11. Marchesi JR, Adams DH, Fava F., Hermes GDA, Hirschfeid GM, Hold G, Quraishi MN, Kinross J, Smidt H, Tuohy KM, Thomas LV, Zoetendal EG, Hart A. The gut microbiota and host health: a new clinical frontier. Gut. 2016; 65(2):330-339.
12. 12. Jones ML, Martoni CJ, Parent M, Prakash S. Cholesterol-lowering efficacy of a microencapsulated bile salt hydrolase-activity Lactobacillus reuteri NCIMB 30243 yoghurt formulation in hypercholesterolaemic adults. Br J Nutr. 2012; 107:1505-1513.
13. 13. Choi SB, Lew LC, Yeo SK, Nair Parvathy S, Liong MT. Probiotics and the BSH-related cholesterol lowering mechanism: a Jekyll and Hyde scenario. Crit Rev Biotechnol. 2015; 35(3):392-401.
14. 14. Gerard C., Vidal H. Impact of Gut Microbiota on Host Glycemic Control. Front. Endocrinol. (Lausanne). 2019; 10:29.
15. 15. Янковский ДС, Дымент ГС. Микрофлора и здоровье человека К.: «Червона Рута-Турс»; 2008.
16. 16. Волосовець ОП, Прохорова МЛ, Кривопустов СП, Бичкова НГ, Слюсар НА. Ефективність мультипробіотика «Симбітер» у комплексному лікуванні атопічного дерматиту та дерматореспіраторного синдрому у дітей. Современная педиатрия. 2010; 29(1):168-171.
17. 17. Манько АМ, Непорада КС, Сухомлин АА, Берегова ТВ, Янковський ДС. Експериментальна корекція мультипробіотиком «Симбітер ацидофільний» патологічних змін у органах ротової порожнини за умов тривалої гіпоацидності. Український стоматологічний альманах. 2010; 6:3-7.
18. 18. Крамарьов СА, Выговская ОВ, Янковский ДС, Дымент ГС. Опыт применения мультипробиотика Симбитер в клинике детских инфекций. Современная педиатрия. 2013; 4:114-120.
19. 19. Янковский Д.С., Широбоков В.П., Дымент Г.С. Микробиом. К.: ФЛП Верес О.И; 2017. 640 с.
20. 20. Михальчишин ГП, Боднар ПМ, Кобиляк НМ. Ефект пробіотиків на рівень прозапальних цитокінів у пацієнтів з діабетом 2-го типу та неалкогольною жировою хворобою печінки. Лікарська справа. 2013; (2):56-62.
21. 21. Kobyliak N, Falalyeyeva T, Bodnar P, Beregova T. Probiotics Suulemented with Omega-3 Fatty Acids are more effective for Hepatic Steatosis Reduction in an Animal Model of Obesity. Probiotics Antimicrob. Proteins. 2017; 9(2):123-130.
22. 22. Migani A, Vayssilov GN, Bromley ST, Illas F, Neyman KM. Dramatic reduction of the oxygen vacancy formation energy in ceria practices: a possible key to their remarkable reactivity at the nanoscale. J Mater Chem. 2010; 20:10535-10546.
23. 23. Celardo I, Traversa E, Ghibelli L. Cerium oxide nanoparticles: a promise for applications in therapy. J. Experim. Therapeutics and Oncology. 2011; 9:47-51.
24. 24. Caputo F, Mameli M, Sienkiewicz A, Licoccia S, Stellacci F, Ghibelli L, Traversa E. A novel synthetic approach of cerium oxide nanoparticles with improved biomedical activity. Sci Rep. 2017; 7(1):4636. doi: 10.1038/s41598-017-04098-6.
25. 25. Moridi H, Hosseini SA, Shateri H, Kheiripour N, Kaki A, Hatami M, Ranjbar A. Protective effect of cerium oxide nanoparticle on sperm quality and oxidative damage in malathion-induced testicular toxicity in rats: An experimental study. Int J Reprod Biomed (Yazd). 2018; 16(4):261-266.
26. 26. Louro H, Saruga A, Santos J, Pinhão M, Silva MJ. Biological impact of metal nanomaterials in relation to their physicochemical characteristics. Toxicology in Vitro. 2019; 56:172-183.
27. 27. Kobyliak N, Abenavoli L, Kononenko L, Kyriienko D, Spivak M. Neuropathic diabetic foot ulcers treated with cerium dioxide nanoparticles: A case report. Diabetes Metab Syndr. 2019; 13(1):228-234.
28. 28. Beyreuther K, Biesalski HK, Fernstrom JD, Grimm P, Hammes WP, Heineman U, Kempski J, Stehle P, Steinhart H, Walker R. Consensus meeting: Monosodium glutamate – An update. European Journal of Clinical Nutrition. 2007; 61(3):304-313.
29. 29. Maluly HDB, Arisseto-Bragotto AP, Reyes FGR. Monosodium glutamate as a tool to reduce sodium in foodstuffs: Technological and safety aspects. Food Sci Nutr. 2017; 5(6):1039-1048. doi: 10.1002/fsn3.499. eCollection 2017 Nov.
30. 30. Kondro М, Mykhalсhyshyn G, Bodnar P, Kobylіak N, Falalyeyeva T., Metabolіс profіle and morfo-funсtіonal state of the lіver іn rats wіth glutamate-іnduсed obesіty. Wydawсa Unіwersytet Medyсzny w Lublіnіe Сurrent Іssues іn Pharmaсy and Medісal Sсіenсes. 2013; 4(26):379–381.
31. 31. Sasaki Y, Shimada T, Iizuka S, Suzuki W, Makihara H, Teraoka R, Tsuneyama K, Hokao R, Aburada M. Effects of bezafibrate in nonalcoholic steatohepatitis model mice with monosodium glutamate-induced metabolic syndrome. Eur J Pharmacol. 2011; 662(1-3):1-8.
32. 32. Gohda E, Nakamura S, Yamamoto I, Minowada J. Hepatocyte growth factor––pleiotropic cytokine produced by human leukemia cells. Leuk Lymphoma. 1995; 19:197-205.
33. 33. Matsumoto K, Nakamura T. Emerging multipotent aspects of hepatocyte growth factor. J Biochem. 1996; 119(4):591-600.
34. 34. Morishita R, Aoki M, Hashiya N, Yamasaki K, Kurinami H, Shimizu S, Makino H, Takesya Y, Azuma J, Ogihara T. Therapeutic angiogenesis using hepatocyte growth factor (HGF). Curr Gene Ther. 2004; 4:199-206.
35. 35. Nakamura T, Sakai K, Nakamura T, Matsumoto K. Hepatocyte growth factor twenty years on: Much more than a growth factor. J Gastroenterol Hepatol. 2011; 26(Suppl 1):188-202.
36. 36. Sanabria ER, Pereira MF, Dolnikoff MS, Andrade IS, Ferreira AT, Cavalheiro EA, Fernandes MJ: Deficit in hippocampal long-term potentiation in monosodium glutamate-treated rats. Brain Res Bull. 2002; 59:47-51.
37. 37. Спивак Н.Я., Носенко Н.Д., Жолобак Н.М., Щербаков А.Б., Резников А.Г., Иванова О.С., Иванов В.К., Третьяков Ю.Д. Нанокристалический диоксид церия повышает функциональную активность репродуктивной системы стареющих самцов крыс. Нано- системы:физика, химия, математика. 2013; 4(1):72-77.
38. 38. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidiniumthiocyanate-phenol-chloroform extraction. Anal Biochem. 1987; 162(1):156-159.
39. 39. Лепехова С.А., Лепехова С.А., Лепехова С.А., Апарцин К.А., Апарцин К.А., Апарцин К.А., Искра А.И. Роль фактора роста гепатоцитов в регенерации печении. Фундаментальные исследования. 2014; 7-1:187-192.
40. 40. Oro D, Yudina T, Fernandez-Varo G, Casals E, Reichenbach V, Casals G, Gonzalez de la Presa B, Sandalinas S, Carvajal S, Puntes V, Jimenez W: Cerium oxide nanoparticles reduce steatosis, portal hypertension and display anti-inflammatory properties in rats with liver fibrosis. J Hepatol 2015;
41. 41. Gomes A.C., Goffmann C., Mota G.F. The human gut microbiota: Metabolism and perspective in obesity. Gut Microbes. 2018; 9(4):308-325.
42. 42. Abenavoli L., Scarpellini E., Colica C., Boccuto L., Salehi B., Sharifi-Rad J., Aiello V., Romano B., De Lorenzo A., Izzo A.A., Capasso R. Gut Microbiota and Obesity: A Role for Probiotics. Nutrients. 2019; 11(11):2690. doi: 10.3390/nu11112690.
43. 43. Эгшатян Л.В., Кушханашхова Д.А., Ермилова Е.С., Аскерханов Р.Г. Микробиота кишечника у пациентов с ожирением и после бариатрических операций. Эндокринная хирургия. 2019; 13(1):5-16.
44. 44. Yan A.W., Fouts D.E., Brandl J. et al. Enteric dysbiosis associated with a mouse model of alcoholic liver disease. Hepatology. 2011; 53(1):96-105.
45. 45. Savcheniuk, О., Kobyliak, N., Kondro, M., Virchenko, O., Falalyeyeva, T. and Beregova, T. Short-term periodic consumption of multiprobiotic from childhood improves insulin sensitivity, prevents development of non-alcoholic fatty liver disease and adiposity in adult rats with glutamate-induced obesity. BMC Complementary and Alternative Medicine. 2014;14:247.