THE ROLE OF MITOCHONDRIAL DYSFUNCTION IN THE DEVELOPMENT OF NON-ALCOHOLIC FATTY LIVER DISEASE
Abstract
Examined 65 patients with verified NASH. The age of the patients ranged from 23 to 67 years. Among them were 36 (55.4%) women and 29 (44.6%) men. The control group consisted of 20 healthy individuals. The effectiveness of complex therapy with the inclusion of the drug L-carnitine, deproteinized hemoderivat of calves and folic acid was studied. The presence of carnitine insufficiency, hyperhomocysteinemia, increase in the level of proinflammatory cytokines in all patients with NASH. After a month of treatment with complex therapy, the level of L-carnitine increased from 14.5 (13.1, 15.7) μmol/l to 31.1 (28.8, 34.1) μmol/l (p<0.001), homocysteine decreased to subnormal figures - 11.8 (11.0, 12.8) μmol/l (p<0.001). When studying the cytokine profile in the group after treatment, a significant decrease in the level of proinflammatory cytokines was revealed. The use of complex therapy with the inclusion of drugs L-carnitine, deproteinized hemoderevate blood of calves as an antihypoxant and folic acid has a positive effect on the clinical course of the disease, contributes to the elimination of L-carnitine deficiency, hyperhomocysteinemia, a decrease in the level of pro-inflammatory cytokines.
About the Authors
T. D. Zvyagintseva
North-Western State Medical University named after I. I. Mechnikov
Russian Federation
Russian Federation
S. V. Glushchenko
North-Western State Medical University named after I. I. Mechnikov
Russian Federation
Russian Federation
References
1. Kleiner D., Brunt E. Non-alcoholic fatty liver disease: pathologic patterns and biopsy evaluation in clinical research. Semin Liver Dis 2012; 32: 003-13.
2. Musso G., Gambino R., Cassader M. Non-alcoholic fatty liver disease from pathogenesis to management: an update. Obesity Reviews 2010; 11: 6: 430-45.
3. Lopaschuk G.D., Ussher J. R., Folmes C. D.L. et al. Myocardial fatty acid metabolism in health and disease. Physiol Rev 2010; 90: 1: 207-58.
4. Noland R.C., Koves T. R., Seiler S. E. et al. Carnitine insufficiency caused by aging and overnutrition compromises mitochondrial performance and metabolic control. J Biol Chem 2009; 284: 34: 22840-52.
5. Sharma Sh., Black St. M. Carnitine homeostasis, mitochondrial function, and cardiovascular disease. Drug Disc Today Dis Mech 2009; 6: 1-4: e31-e39.
6. Indiveri C., Iacobazzi V., Tonazzi A. et al. The mitochondrial carnitine/acylcarnitine carrier: Function, structure and physiopathology. Mol Aspects Med 2011; 32: 4-6: 223-33.
7. Lee K., Kerner J., Hoppel Ch. L. Mitochondrial camitinepalmitoyl-transferase 1a (CPT1a) is part of an outer membrane fatty acid transfer complex. J Biol Chem 2011; 286: 29: 25655-62.
8. Li H., Ying H., Hu A. et al. Therapeutic Effect of Gypenosides on Nonalcoholic Steatohepatitis via Regulating Hepatic Lipogenesis and Fatty Acid Oxidation. Biol Pharm Bull. 2017; 40 (5): 650-57.
9. Tonazzi A., Giangregorio N., Console L. et al. Nitric oxide inhibits the mitochondrial carnitine/acylcarnitine carrier through reversible S-nitrosylation of cysteine 136. Biochim Biophys Acta 2017; 1858 (7): 475-82.
10. Tiniakos D.G., Vos M. B., Brunt E. M. Nonalcoholic fatty liver disease: pathology and pathogenesis. Annu Rev Pathol 2010; 5: 145-71.
11. Polyzos S.A., Kountouras J., Zavos C. Curr Nonalcoholic fatty liver disease: the pathogenetic roles of insulin resistance and adipocytokines. Мol Med 2009; 9: 3: 299-314.
12. Furuno T., Kanno T., Arita K. et al. Roles of long chain fatty acids and carnitine in mitochondrial membrane permeability transition. Biochem Pharmacol 2001; 62: 8: 1037-46.
13. Oyanagi E., Yano H., Kato Y. et al. L-Carnitine suppresses oleic acid-induced membrane permeability transition of mitochondria. Cell Biochem Funct 2008; 26: 7: 778-86.
14. Pillich R.T., Scarsella G., Risuleo G. Reduction of apoptosis through the mitochondrial pathway by the administration of acetyl-L-carnitine to mouse fibroblasts in culture. Exp Cell Res 2005; 306: 1: 1-8.
15. Mel’nik A.V., Voloshchouk N. I., Pentyuk N. O. et al. Role of Hydrogen Sulfide and Sulfur-Containing Amino Acids in Regulation of Tone of Smooth Muscles of the Vascular Wall in Rats. Neurophysiol 2010; 2: 126-31.
16. Grattagliano I., Bari O., Bernardo T. C. et al. Role of mitochondria in nonalcoholic fatty liver disease-from origin to propagation. Clin Biochem 2012; 45: 610-18.
17. Ivanov I., Heydeck D., Hofheinz K. et al. Molecular enzymology of lipoxygenases. Archives of Biochemistry and Biophysics 2010; 503: 2: 161-74.
18. Maron A.B., Loscalzo J. The Treatment of Hyperhomocysteinemia. Annu Rev Med 2009; 60: 39-54.
19. Naik A., Belic A., Zander U. M., Rozman D. Molecular interactions between NAFLD and xenobiotic metabolism. Frontiers sn genetics 2013; 4: 2: 75-88.
20. Newton J. L. Systemic Symptoms in Non-Alcoholic Fatty Liver Disease. Dig Dis 2010; 28: 1: 214-19.
21. Farrell G.C., McCullough A.J., Day C. P. et al. Non-Alcoholic Fatty Liver Disease: A Practical Guide. 2013, Wiley-Blackwell - 324p.
22. Powel E.E., Jonsson J. R., Clouston A. D. Metabolic Factors and Non-Alcoholic Fatty Liver Disease as Co-Factors in Other Liver Diseases. Dig Dis 2010; 28: 1: 186-91.
Review
For citations:
Zvyagintseva T.D., Glushchenko S.V. THE ROLE OF MITOCHONDRIAL DYSFUNCTION IN THE DEVELOPMENT OF NON-ALCOHOLIC FATTY LIVER DISEASE. Experimental and Clinical Gastroenterology. 2018;(2):37-43. (In Russ.)
Views:
248
Email this article 