CLINICAL FEATURES OF THE ANTIOXIDANT SYSTEM AND SOME CANDIDATE GENES POLYMORPHISMS IN THE PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Background. Non-alcoholic fatty liver disease (NAFLD) is the most common among diffuse liver diseases worldwide. In recent years, the relationship between lipid metabolism disorders in the liver, changes in antioxidant status and polymorphism of genes affecting the metabolism of fatty acids, in NAFLD have been emphasized. This article demonstrates the results of the study of the antioxidant system enzymes, polymorphisms of some candidate genes and some polymorphisms genes of the antioxidant system in NAFLD. Methods. A total of 114 patients participated in the study, including 67 patients with verified NAFLD and 47 patients with irritable bowel syndrome who represented the control group. All patients underwent the evaluation of antioxidant status and PCR-RFLP (polymerase chain reaction and restriction fragment length polymorphism) analysis of the GSTA, GSTP, SOD2, PPARA, UCP2, and UCP3 genes. Results. In patients with NAFLD, an increase in the activity of the lipid peroxidation (LPO) process was detected, while the expected decrease in the activity of the enzymes of the antioxidant defense system (glutathione-S-transfer-ase, catalase) was not observed. The analysis of genetic study has revealed a statistically significant increase in the detection frequency of UCP-2 gene polymorphism and a more frequent combination of single nucleotide polymorphisms in the UCP2 and UCP3 genes in patients with NAFLD, in contrast to the control group. Conclusion. The results of the evalyation of the antioxidant status in patients with NAFLD, on the one hand, demonstrate one of the components of the NAFLD pathogenesis - the enhancement of LPO; and on the other - the probable activation of hepatocyte protective systems in response to damage -no decrease and even an increase in the activity of antioxidant enzymes. The data obtained in the genetic study indicate a possible association of the detected polymorphisms of the UCP2 and UCP3 genes with components of the NAFLD pathogenesis.

Full Text

Restricted Access

About the authors

I. V Lapinsky

North-Western State Medical University n.a. I.I. Mechnikov

Email: lapinsky85@yandex.ru
Assistant at the Department of Propaedeutics of Internal Diseases, Gastroenterology and Dietology

E. B Avalueva

North-Western State Medical University n.a. I.I. Mechnikov

I. G Bakulin

North-Western State Medical University n.a. I.I. Mechnikov

V. A Dadali

North-Western State Medical University n.a. I.I. Mechnikov

A. A Topanova

Almazov National Medical Research Centre

E. V Skazyvaeva

North-Western State Medical University n.a. I.I. Mechnikov

A. V Pushkina

North-Western State Medical University n.a. I.I. Mechnikov

References

  1. Bellentani S., Scaglioni F., Marino M., Bedogni G. Epidemiology of non-alcoholic fatty liver disease. Dig. Dis. 2010;28:155-61. doi: 10.1159/000282080.
  2. Rolo A.P., Teodoro J.S., Palmeira C.M. Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis. Free Radic. Biol. Med. 2012;52:59-69. doi: 10.1016/j.freeradbiomed.2011.10.003.
  3. Бакулин И.Г., Сандлер Ю.Г., Кейян В.А. и др. Оценка стеатоза печени с помощью неинвазивного метода: миф или реальность? Доктор.Ру. 2015;12(113):57-64. [Bakulin I.G., Sandler Yu.G., Kejyan КА., et al. Evaluation of liver steatosis by non-invasive method: myth or reality? Doktor.Ru. 2015;12(113):57-64. (In Russ.)].
  4. Fassio E., Alvarez E., Dominguez N., et al. Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies. Hepatology. 2004;40:820-26. doi: 10.1002/hep.20410.
  5. Charlton M.R., Burns J.M., Pedersen R.A., et al. Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. Gastroenterology. 2011;141:1249-53. doi: 10.1053/j.gastro.2011.06.061.
  6. Бакулин И.Г., Шаликиани Н.В. Патогенез алкогольного заболевания печени: современные представления. Доктор.Ру 2015;12(113):7-14. [Bakulin LG., Shalikiani N.V Pathogenesis of alcoholic liver disease: modern concepts. Doktor.Ru. 2015;12(113):7-14. (In Russ.)].
  7. Belfort R., Harrison S.A., Brown K., et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis N. Engl. J. Med. 2006;355:2297-307. DOI: 10.1056/ NEJMoa060326.
  8. Betrapally N.S., Gillevet P.M., Bajaj J.S. Changes in the Intestinal Microbiome and Alcoholic and Nonalcoholic Liver Diseases: Causes or Effects? Gastroenterology. 2016;150(8):1745-55. Doi: 10.1053/j. gastro.2016.02.073.
  9. Caldwell S.H., Swerdlow R.H., Khan E.M., et al. Mitochondrial abnormalities in non-alcoholic steatohepatitis. Hepatol. 1999;31:430-34.
  10. Chatham J., Chacko V.P., Arnold C., et al. Alterations in H. liver ATP homeostasis in human nonalcoholic steatohepatitis: a pilot study. JAMA. 1999;282: 1659-64.
  11. Serviddio G., Bellanti F., Tamborra R., et al. Alterations of hepatic ATP homeostasis and respiratory chain during development of non-alcoholic steatohepatitis in a rodent model. Eur J. Clin. Invest. 2008;38:245-52. doi: 10.1111/j.1365-2362.2008.01936.x.
  12. Betrapally N.S., Gillevet P.M., Bajaj J.S. Changes in the Intestinal Microbiome and Alcoholic and Nonalcoholic Liver Diseases: Causes or Effects? Gastroenterology. 2016;150(8):1745-55. Doi: 10.1053/j. gastro.2016.02.073.
  13. Timlin M.T., Parks E.J. Temporal pattern of de novo lipogenesis in the postprandial state in healthy men. Am. J. Clin. Nutr. 2005;81:35-42. Doi: 10.1093/ ajcn/81.1.35.
  14. Donnelly K.L., Smith C.I., Schwarzenberg S.J., et al. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease.Am. J. Clin. Invest. 2005;115:1343-51. doi: 10.1172/JCI23621.
  15. De C.D., Pauwels M., Van den Branden C. Alterations of peroxisomes in steatosis of the human liver: a quantitative study. Hepatology. 1995;22:744-52.
  16. Sunny N.E., Parks E.J., Browning J.D., Burgess S.C. Excessive hepatic mitochondrial TCA cycle and gluconeogenesis in humans with nonalcoholic fatty liver disease. Cell. Metab. 2011;14:804-10. Doi:
  17. W16/j.cmet.2011.11.004.
  18. Wei X., Wang D., Topczewski F., Pagliassotti M.J. Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells. Am. J. Physiol. Endocrinol. Metab. 2006;291:275-81. Doi: 10.1152/ ajpendo.00644.2005.
  19. Muriel P. Role of free radicals in liver diseases. Hepatol. Int. 2009;3:526-36.
  20. Houstis N.,. Rosen E.D., Lander E.S. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature. 2006;440:944-8. Doi:: 10.1038/ nature04634.
  21. Arrese M., Karpen S.J. Nuclear receptors, inflammation, and liver disease: insights for cholestatic and fatty liver diseases. Clin. Pharmacol. Ther. 2010;87:473 - 78.
  22. Wagner M., Zollner G., Trauner M. Nuclear receptors in liver disease. Hepatology. 2011;53:1023-34. doi: 10.1002/hep.24148.
  23. Spiegelman B.M. PPARy: adipogenic regulator and thiazolidinedione receptor. Diabetes. 1998; 4:507-14.
  24. Бондарева Э.А., Андреев Р.С., Якушкин А.В. и др. Полиморфизм генов разобщающих белков семейства UCP у футболистов: в поисках функциональной роли. Физиология человека. 2016;42(6):70-80.
  25. Schrauwen P., Hoeks J., Hesselink M.K. Putative function and physiological relevance of the mitochondrial uncoupling protein-3: involvement in fatty acid metabolism? Prog. Lipid. Res. 2006;45(1):17-41. doi: 10.1016/j.plipres.2005.11.001.
  26. Boudina S., Graham T.E. Mitochondrial function/ dysfunction in white adipose tissue. Exp. Physiol. 2014;99(9):1168-78. Doi: 10.1113/ expphysiol.2014.081414.
  27. Farhangi M., Mohseni F., Farajnia S., Jafarabadi M. Major components of metabolic syndrome and nutritional intakes in different genotype of UCP2 -866G/A gene polymorphisms in patients with NAFLD. Transl. Med. 2016;14:177. Doi: 10.1186/ s12967-016-0936-3.
  28. Brondani L.A., Assmann T.S., Duarte G.C., et al. The role of the uncoupling protein 1 (UCP1) on the development of obesity and type 2 diabetes mellitus. Arq. Bras. Endocrinol. Metabol. 2012;56:215.
  29. Wang C., Gong J., Wu H. Development of gene polymorphisms in meditators of nonalcoholic fatty liver disease. Biomed. Rep. 2017;7(2):95-104. doi: 10.3892/br.2017.926.
  30. Комелина Н.П., Амерханов З.Г. Разобщающие белки UCP2 и UCP3 митохондрий печени и мышц суслика spermophilus undulates в отличие от UCP1 бурого жира не способны к неспецифическому транспорту пирувата. Биологические мембраны. Журнал мембранной и клеточной биологии. 2013;30(5-6): 412-21.
  31. Leclercq A. Antioxidant defence mechanisms: new players in the pathogenesis of non-alcoholic steatohepatitis? Clin. Sci.2004;106:235-37. doi: 10.1042/CS20030368.
  32. Leiers B., Kampkötter A., Grevelding C.G., et al. A stress-responsive glutathione S-transferase confers resistance to oxidative stress in Caenorhabditis elegans. Radic. Biol. Med. 2003;34(11):1405-15. doi: 10.1016/S0891-5849(03)00102-3
  33. Fuchs M., Sanyal A.J. Lipotoxicity in NASH. J. Hepatol. 2012;56:291-3. doi: 10.1016/j.jhep.2011.05.019.
  34. Videla L.A., Rodrigo R., Orellana M., et al. Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients. Clin. Sci. 2004;106:261-68. doi: 10.1042/CS20030285.
  35. Carmiel-Haggai M., Cederbaum A.I., Nieto N. A high-fat diet leads to the progression of non-alcoholic fatty liver disease in obese rats. FASEB J. 2005;19:136-38. doi: 10.1096/fj.04-2291fje.
  36. Perlemuter G., Davit-Spraul A., Cosson C., et al. Increase in liver antioxidant enzyme activities in nonalcoholic fatty liver disease. Liver Int. 2005;25:946-
  37. doi: 10.1111/j.1478-3231.2005.01126.x.
  38. Kohjima M., Enjoji M., Higuchi N., et al. Re-evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease. Int. J. Mol. Med. 2007;20:351-58.
  39. Li L. Yang X. The Essential Element Manganese, Oxidative Stress, and Metabolic Diseases: Links and Interactions. Oxid. Med. Cell. Longev. 2018:7580707. doi: 10.1155/2018/7580707.
  40. Borrelli A., Bonelli P., Tuccillo FM., et al. Role of gut microbiota and oxidative stress in the progression of non-alcoholic fatty liver diseaseto hepatocarcinoma: Current and innovative therapeutic approaches. Redox Biol. 2018;15:467-79. Doi: 10.1016/j. redox.2018.01.009.
  41. Yates M.S., Tran Q.T., Dolan P.M., et al. Genetic versus chemoprotective activation of Nrf2 signaling: overlapping yet distinct gene expression profiles between Keap1 knockout and triterpenoid-treated mice. Carcinogenesis. 2009;30:1024-31. doi: 10.1093/carcin/bgp100.
  42. Променашева Т.Е. Роль оксидативного стресса и системы глутатиона в патогенезе неалкогольной жировой болезни печени. Бюллетень ВСНЦ СО РАМН. 2014;5(99):80-3.
  43. Hashemi M., Eskandari-Nasab E., Fazaeli A., et al. Association of genetic polimorphisms of glutathione-S-transferase genes (GSTT1, GSTM1 and GSTP1) and susceptibility to nonalcoholic fatty liver disease in Zahedan. DNA Cell. Biol. 2012;31(5):7-672. doi: 10.2217/bmm.12.61.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2018 Bionika Media

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies