RESEARCH PAPER
Relationships between serum selenium and zinc concentrations versus profibrotic and proangiogenic cytokines (FGF-19 and endoglin) in patients with alcoholic liver cirrhosis
| 1 | Department of Internal Medicine, Medical University of Lublin, Lublin, Poland |
| 2 | Department of Family Medicine, Medical University of Lublin, Lublin, Poland |
| 3 | Department of Medical Chemistry, Medical University of Lublin, Lublin, Poland |
| 4 | Department of Analytical Chemistry, Medical University of Lublin, Lublin, Poland |
| 5 | II Department of Radiology, Medical University of Lublin, Lublin, Poland |
| 6 | Individual Medical Practice, Lublin, Poland |
| 7 | Department of Ethics and Human Philosophy, Medical University of Lublin, Lublin, Poland |
| 8 | Institute of Rural Medicine, Lublin, Poland |
Ann Agric Environ Med 2017;24(3):544–548
KEYWORDS:
TOPICS:
ABSTRACT:
Introduction and objective:
Liver cirrhosis is a disease involving the liver parenchyma, which is characterised by fibrosis and impaired architectonics of the parenchyma with regenerative nodules. The aim of the study was to determine the relationship between stage of alcoholic liver cirrhosis, concentrations of selenium, zinc and profibrotic and proangiogenic cytokines (FGF-19, ENG).
Material and methods:
The study included 99 patients with alcoholic cirrhosis and 20 healthy subjects. Ion chromatography with UV/VIS detection was used for determination of zinc ions in the previously mineralized serum samples. The measurements of selenium were performed with the ContrAA700 high-resolution continuum source graphite tube atomic absorption spectrometer. ELISA was used to determine concentration of FGF-19 and ENG in serum samples.
Results:
Concentrations of zinc and selenium were significantly decreased in cirrhotic patients (p<0.001 for both). The highest concentration of FGF-19 was found in Child-Pugh stage C liver cirrhosis patients (806.9±650.3 pg/ml), and was significantly higher than observed in controls (p=0.005) and stage A patients (compensated cirrhosis) (p=0.02). The highest concentration of ENG was demonstrated in the control group (3.24±148 ng/ml) while the lowest in patients with decompensated cirrhosis (7.32±5.39 ng/ml and 7.92±4.18 ng/ml for stage B and C; p=0.03 and p=0.02, respectively). The use of the multiple-variable model demonstrated that the independent factors affecting the concentration of ENG were the concentration of bilirubin (p=0.02), INR (p=0.01) and duration of alcohol abuse (p=0.02). The independent determinants of FGF-19 concentrations were found to be the stage (severity) of liver cirrhosis (p=0.04) and INR (p=0.03).
Conclusions:
Concentrations of zinc and selenium in serum of patients with alcoholic liver cirrhosis are not independently related to concentrations of FGF-19 and ENG.
Liver cirrhosis is a disease involving the liver parenchyma, which is characterised by fibrosis and impaired architectonics of the parenchyma with regenerative nodules. The aim of the study was to determine the relationship between stage of alcoholic liver cirrhosis, concentrations of selenium, zinc and profibrotic and proangiogenic cytokines (FGF-19, ENG).
Material and methods:
The study included 99 patients with alcoholic cirrhosis and 20 healthy subjects. Ion chromatography with UV/VIS detection was used for determination of zinc ions in the previously mineralized serum samples. The measurements of selenium were performed with the ContrAA700 high-resolution continuum source graphite tube atomic absorption spectrometer. ELISA was used to determine concentration of FGF-19 and ENG in serum samples.
Results:
Concentrations of zinc and selenium were significantly decreased in cirrhotic patients (p<0.001 for both). The highest concentration of FGF-19 was found in Child-Pugh stage C liver cirrhosis patients (806.9±650.3 pg/ml), and was significantly higher than observed in controls (p=0.005) and stage A patients (compensated cirrhosis) (p=0.02). The highest concentration of ENG was demonstrated in the control group (3.24±148 ng/ml) while the lowest in patients with decompensated cirrhosis (7.32±5.39 ng/ml and 7.92±4.18 ng/ml for stage B and C; p=0.03 and p=0.02, respectively). The use of the multiple-variable model demonstrated that the independent factors affecting the concentration of ENG were the concentration of bilirubin (p=0.02), INR (p=0.01) and duration of alcohol abuse (p=0.02). The independent determinants of FGF-19 concentrations were found to be the stage (severity) of liver cirrhosis (p=0.04) and INR (p=0.03).
Conclusions:
Concentrations of zinc and selenium in serum of patients with alcoholic liver cirrhosis are not independently related to concentrations of FGF-19 and ENG.
CORRESPONDING AUTHOR:
Andrzej Prystupa
Department of Internal Medicine, Medical University of Lublin, Lublin, Poland, Staszica, 20-950 Lublin, Poland
REFERENCES (32):
| 1. | Blachier M, Leleu H, Peck-Radosavljevic M, Valla D-C, Roudot-Thoraval F. The burden of liver disease in Europe: A review of available epidemiological data. J Hepatol. 2013; 25(3): 593–608. |
| 2. | World Health Organization. European status report on alcohol and health: World Health Organization. Regional Office for Europe, 2010. |
| 3. | Mokdad A, Lopez A, Shahraz S, et al. Liver cirrhosis mortality in 187 countries between 1980 and 2010: a systematic analysis. BMC Medicine 2014; 12: 145. |
| 4. | Zhou W-C, Zhang Q-B, Qiao L. Pathogenesis of liver cirrhosis. World J Gastroenterol. 2014; 20(23): 7312–7324. |
| 5. | Robak E, Gerlicz Z. Wybrane cytokiny proangiogenne w twardzinie układowej. Postepy Hig Med Dosw. 2014; 68: 1472–1482. |
| 6. | Westphal J, Willems H, Schalwijk C, Ruiter D, de Waal R. A new 180-kDa dermal endothelial cell activation antigen: in vitro and in situ characteristics. J Invest Dermatol. 1993; 100: 27–34. |
| 7. | Meurer S, Alsamman M, Sahin H, Wasmuth H, Kisseleva T, Brenner D, et al. Overexpression of endoglin modulates TGF-β1-signalling pathways in a novel immortalized mouse hepatic stellate cell line. PLoS One. 2013; 8(2): e56116. |
| 8. | Yagmur E, Rizk M, Stanzel S, Hellerbrand C, Lammert F, Trautwein C, et al. Elevation of endoglin (CD105) concentrations in serum of patients with liver cirrhosis and carcinoma. Eur J Gastroenterol Hepatol. 2007; 19(9): 755–761. |
| 9. | Wunsch E, et al. Expression of hepatic Fibroblast Growth Factor 19 is enhanced in Primary Biliary Cirrhosis and correlates with severity of the disease. Sci Rep. 2015; 5: 13462. |
| 10. | Hyeon J, Ahn S, Lee J, Song D, Park C. Expression of fibroblast growth factor 19 is associated with recurrence and poor prognosis of hepatocellular carcinoma. Dig Dis Sci. 2013; 58(7): 1916–1922. |
| 11. | Prystupa A, Błażewicz A, Kiciński P, Sak JJ, Niedziałek J, Załuska W. Serum Concentrations of Selected Heavy Metals in Patients with Alcoholic Liver Cirrhosis from the Lublin Region in Eastern Poland. Int J Environ Res Public Health. 2016; 13(6): E582. |
| 12. | Omran D, Darweesh S, Fouad H, Mahmoud M, Saif S, Fared A, et al. Serum Zinc Deficiency and its Relation to Liver Fibrosis in Chronic HCV: a Real-Life Egyptian Study. Biol Trace Elem Res. 2017; doi: 10.1007/s12011-017-0938-x. |
| 13. | Burk R, Hill K, Motley A, Byrne D, Norsworthy B. Selenium deficiency occurs in some patients with moderate-to-severe cirrhosis and can be corrected by administration of selenate but not selenomethionine: a randomized controlled trial. Am J Clin Nutr. 2015; 102(5): 1126–1133. |
| 14. | Pugh R, Murray-Lyon I, Dawson J, Pietroni M, et al. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973, 60(8): 646–9. |
| 15. | Błażewicz A, Baj T, Świeboda R, Świątek Ł. Determination of heavy metals in aerial part of hyssop (Hyssopus officinalis L.) using high performance ion chromatography with the aid of a linear and non-linear weighted least-squares regression model. Pol J Environ Stud. 2007; 16: 191–198. |
| 16. | Błażewicz A, Klatka M, Astel A, Korona-Glowniak I, Dolliver W, Szwerc W, et al. Serum and urinary selenium levels in obese children: a cross-sectional study. J Trace Elem Med Biol. 2015; 29: 116–122. |
| 17. | Burk R, Hill K, Motley A, Byrne D, Norsworthy B. Selenium deficiency occurs in some patients with moderate-to-severe cirrhosis and can be corrected by administration of selenate but not selenomethionine: a randomized controlled trial. Am J Clin Nutr. 2015; 102(5): 1126–1132. |
| 18. | Han J, Liang H, Yi J, Tan W, He S, Wang S, et al. Long-Term Selenium-Deficient Diet Induces Liver Damage by Altering Hepatocyte Ultrastructure and MMP1/3 and TIMP1/3 Expression in Growing Rats. Biol Trace Elem Res. 2017; 175(2): 396–404. |
| 19. | Zhang Z, Guo Y, Qiu C, Deng G, Guo M. Protective Action of Se-Supplement Against Acute Alcoholism Is Regulated by Selenoprotein P (SelP) in the Liver. Biol Trace Elem Res. 2017; 175(2): 375–387. |
| 20. | Ozkol H, Bulut G, Balahoroglu R, Tuluce Y, Ozkol HU. Protective Effects of Selenium, N-Acetylcysteine and Vitamin E Against Acute Ethanol Intoxication in Rats. Biol Trace Elem Res. 2017; 175(1): 177–185. |
| 21. | Kalishwaralal K, Jeyabharathi S, Sundar K, Muthukumaran A. Sodium selenite/selenium nanoparticles (SeNPs) protect cardiomyoblasts and zebrafish embryos against ethanol induced oxidative stress. J Trace Elem Med Biol. 2015; 32: 135–144. |
| 22. | Vallee B, Falchuk K. The biochemical basis of zinc physiology. Physiol Rev. 1993; 73: 79–118. |
| 23. | Keilin D, Mann T. Carbonic anhydrase. Nature. 1939; 144: 442–443. |
| 24. | Oteiza P. Zinc and the modulation of redox homeostasis. Free Radical Biology and Medicine. 2012; 53(9): 1748–1759. |
| 25. | Vallee B, Hoch F. Zinc, a component of yeast alcohol dehydrogenase. Proc Natl Acad Sci USA. 1955; 15, 41(6): 327–338. |
| 26. | Krishna S, Majumdar I, Grishin N. Structural classification of zin fingers: survey and summary. Nucleic Acids Res. 2003, 31(2): 532–550. |
| 27. | Parsons S, Di Silvestro R. Effects of mild zinc deficiency, plus or minus an acute-phase response on galactosamine-induced hepatitis in rats. Br Nutr. 1994; 72: 611–618. |
| 28. | Walker B, Dawson J, Kelleher J, Losowsky M. Plasma and urinary zinc in patients with malabsorption syndromes or hepatic cirrhosis. Gut. 1973; 14(12): 943–948. |
| 29. | Kwon Y, Sasaki R, Meyer K, Ray R. Hepatitis C virus core protein modulates endolglin (CD105) signalling pathway for liver pathogenesis. J Virol. 2017; 9. pii: JVI.01235-17. doi: 10.1128/JVI.01235-17. |
| 30. | Clemente M, Núñez O, Lorente R, Rincón D, Matilla A, Salcedo M, et al. Increased intrahepatic and circulating levels of endoglin, a TGF-beta1 co-receptor, in patients with chronic hepatitis C virus infection: relationship to histological and serum markers of hepatic fibrosis. J Viral Hepat. 2006; 13(9): 625–632. |
| 31. | Saghiri M, Asatourian A, Orangi J, Sorenson C, Sheibani N. Functional role of inorganic trace elements in angiogenesis – Part I: N, Fe, Se, P, Au, and Ca. Crit Rev Oncol Hematol. 2015; 96(1): 129–142. |
| 32. | Rezende V, Barbosa F Jr, Palei A, Cavalli R, Tanus-Santos J, Sandrim V. Correlations among antiangiogenic factors and trace elements in hypertensive disorders of pregnancy. J Trace Elem Med Biol. 2015; 29: 130–135. |
Related articles
