Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Journal of Laboratory Medicine

Official Journal of the German Society of Clinical Chemistry and Laboratory Medicine

Editor-in-Chief: Schuff-Werner, Peter

Ed. by Ahmad-Nejad, Parviz / Bidlingmaier, Martin / Bietenbeck, Andreas / Conrad, Karsten / Findeisen, Peter / Fraunberger, Peter / Ghebremedhin, Beniam / Holdenrieder, Stefan / Kiehntopf, Michael / Klein, Hanns-Georg / Kohse, Klaus P. / Kratzsch, Jürgen / Luppa, Peter B. / Meyer, Alexander von / Nebe, Carl Thomas / Orth, Matthias / Röhrig-Herzog, Gabriele / Sack, Ulrich / Steimer, Werner / Weber, Thomas / Wieland, Eberhard / Winter, Christof / Zettl, Uwe K.


IMPACT FACTOR 2018: 0.389

CiteScore 2018: 0.22

SCImago Journal Rank (SJR) 2018: 0.156
Source Normalized Impact per Paper (SNIP) 2018: 0.089

Online
ISSN
2567-9449
See all formats and pricing
More options …
Volume 42, Issue 1-2

Issues

Dynamic thiol-disulfide homeostasis is disturbed in patients with non-alcoholic fatty liver disease

Mehmet Asil
  • Corresponding author
  • Necmettin Erbakan University, Meram School of Medicine, Department of Internal Medicine, Division of Gastroenterology, Meram, Konya, Turkey, Phone: +905054007407, +903322236587, Fax: +903323237120
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Ramazan Dertli
  • Necmettin Erbakan University, Meram School of Medicine, Department of Internal Medicine, Division of Gastroenterology, Meram, Konya, Turkey
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Murat Biyik
  • Necmettin Erbakan University, Meram School of Medicine, Department of Internal Medicine, Division of Gastroenterology, Meram, Konya, Turkey
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Ramazan Yolacan
  • Necmettin Erbakan University, Meram School of Medicine, Department of Internal Medicine, Meram, Konya, Turkey
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Ozcan Erel
  • Department of Biochemistry, Faculty of Medicine, Yıldırım Beyazıt University, Ankara, Turkey
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Salim Neselioglu
  • Department of Biochemistry, Faculty of Medicine, Yıldırım Beyazıt University, Ankara, Turkey
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Huseyin Ataseven
  • Necmettin Erbakan University, Meram School of Medicine, Department of Internal Medicine, Division of Gastroenterology, Meram, Konya, Turkey
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Hakkı Polat
  • Necmettin Erbakan University, Meram School of Medicine, Department of Internal Medicine, Meram, Konya, Turkey
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Ali Demir
  • Necmettin Erbakan University, Meram School of Medicine, Department of Internal Medicine, Division of Gastroenterology, Meram, Konya, Turkey
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2017-11-27 | DOI: https://doi.org/10.1515/labmed-2017-0018

Abstract

Background:

Oxidative stress has been implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Plasma thiols are major defense mechanisms against oxidative stress and undergo oxidation to form disulfides under oxidative conditions. This study was conducted to investigate thiol-disulfide homeostasis in NAFLD patients.

Methods:

Thirty patients with biopsy proven non-alcoholic steatohepatitis (NASH), 40 patients with simple steatosis and 50 healthy controls were included in the study. Serum total and native thiol concentrations and serum disulfide concentration were measured using the Erel and Neselioglu’s method.

Results:

The mean serum total thiol concentrations in the NASH, simple steatosis and control groups were 415±64 μmol/L, 447±38 μmol/L and 480±37 μmol/L, respectively (p<0.001). The mean serum native thiol concentrations in the NASH, simple steatosis and control groups were 378±62 μmol/L, 416±41 μmol/L and 451±36 μmol/L, respectively (p<0.001). The mean serum disulfide concentrations in the NASH, simple steatosis and control groups were 18.5±6.3 μmol/L, 15.5±4.8 μmol/L and 14.9±3.6 μmol/L, respectively (p=0.005). The native thiol/total thiol ratio was significantly lower and the disulfide/total thiol and disulfide/native thiol ratios were significantly higher in the NASH group than in the simple steatosis and control groups.

Conclusions:

Thiol-disulfide homeostasis is disturbed and shifted toward disulfide side in NAFLD and NASH patients.

Keywords: disulfides; fatty liver; oxidative stress; steatohepatitis; thiols

References

  • 1.

    Younossi ZM, Stepanova M, Afendy M, Fang Y, Younossi Y, Mir H, et al. Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1988 to 2008. Clin Gastroenterol Hepatol 2011;9:524–30.e1; quiz e60.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 2.

    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;34:274–85.Web of ScienceCrossrefPubMedGoogle Scholar

  • 3.

    Sanyal AJ, Campbell-Sargent C, Mirshahi F, Rizzo WB, Contos MJ, Sterling RK, et al. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 2001;120:1183–92.CrossrefPubMedGoogle Scholar

  • 4.

    Oliveira CP, Stefano JT. Genetic polymorphisms and oxidative stress in non-alcoholic steatohepatitis (NASH): a mini review. Clin Res Hepatol Gastroenterol 2015;39(Suppl 1):S35–40.Web of ScienceCrossrefGoogle Scholar

  • 5.

    Abdou RM, Zhu L, Baker RD, Baker SS. Gut microbiota of nonalcoholic fatty liver disease. Dig Dis Sci 2016;61:1268–81.Web of ScienceCrossrefPubMedGoogle Scholar

  • 6.

    Diesen DL, Kuo PC. Nitric oxide and redox regulation in the liver: part II. Redox biology in pathologic hepatocytes and implications for intervention. J Surg Res 2011;167:96–112.Web of ScienceCrossrefPubMedGoogle Scholar

  • 7.

    Turell L, Radi R, Alvarez B. The thiol pool in human plasma: the central contribution of albumin to redox processes. Free Radic Biol Med 2013;65:244–53.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 8.

    Winterbourn CC, Hampton MB. Thiol chemistry and specificity in redox signaling. Free Radic Biol Med 2008;45:549–61.Web of SciencePubMedCrossrefGoogle Scholar

  • 9.

    Circu ML, Aw TY. Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med 2010;48:749–62.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 10.

    Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem 2014;47:326–32.Web of SciencePubMedCrossrefGoogle Scholar

  • 11.

    Ates I, Ozkayar N, Inan B, Yilmaz FM, Topcuoglu C, Neselioglu S, et al. Dynamic thiol/disulphide homeostasis in patients with newly diagnosed primary hypertension. J Am Soc Hypertens 2016;10:159–66.CrossrefWeb of SciencePubMedGoogle Scholar

  • 12.

    Yuksel M, Ates I, Kaplan M, Alışık M, Erel Ö, Saygılı F, et al. The dynamic thiol/disulphide homeostasis in inflammatory bowel disease and its relation with disease activity and pathogenesis. Int J Colorectal Dis 2016;31:1229–31.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 13.

    Ates I, Kaplan M, Yuksel M, Mese D, Alisik M, Erel Ö, et al. Determination of thiol/disulphide homeostasis in type 1 diabetes mellitus and the factors associated with thiol oxidation. Endocrine 2016;51:47–51.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 14.

    Kundi H, Ates I, Kiziltunc E, Cetin M, Cicekcioglu H, Neselioglu S, et al. A novel oxidative stress marker in acute myocardial infarction; thiol/disulphide homeostasis. Am J Emerg Med 2015;33:1567–71.Web of ScienceCrossrefPubMedGoogle Scholar

  • 15.

    Topuz M, Kaplan M, Akkus O, Sen O, Yunsel HD, Allahverdiyev S, et al. The prognostic importance of thiol/disulfide homeostasis in patients with acute pulmonary thromboembolism. Am J Emerg Med 2016;34:2315–9.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 16.

    Chen Y, Dong H, Thompson DC, Shertzer HG, Nebert DW, Vasiliou V. Glutathione defense mechanism in liver injury: insights from animal models. Food Chem Toxicol 2013;60:38–44.CrossrefWeb of SciencePubMedGoogle Scholar

  • 17.

    Day CP, James OF. Steatohepatitis: a tale of two “hits”? Gastroenterology 1998;114:842–5.CrossrefPubMedGoogle Scholar

  • 18.

    Köroğlu E, Canbakan B, Atay K, Hatemi İ, Tuncer M, Dobrucalı A. Role of oxidative stress and insulin resistance in disease severity of non-alcoholic fatty liver disease. Turk J Gastroenterol 2016;27:361–6.Web of ScienceCrossrefPubMedGoogle Scholar

  • 19.

    Petrosillo G, Portincasa P, Grattagliano I, Casanova G, Matera M, Ruggiero FM, et al. Mitochondrial dysfunction in rat with nonalcoholic fatty liver Involvement of complex I, reactive oxygen species and cardiolipin. Biochim Biophys Acta 2007;1767:1260–7.Web of ScienceCrossrefPubMedGoogle Scholar

  • 20.

    Yesilova Z, Yaman H, Oktenli C, Ozcan A, Uygun A, Cakir E, et al. Systemic markers of lipid peroxidation and antioxidants in patients with nonalcoholic fatty liver disease. Am J Gastroenterol 2005;100:850–5.PubMedCrossrefGoogle Scholar

  • 21.

    Nobili V, Parola M, Alisi A, Marra F, Piemonte F, Mombello C, et al. Oxidative stress parameters in paediatric non-alcoholic fatty liver disease. Int J Mol Med 2010;26:471–6.PubMedWeb of ScienceGoogle Scholar

  • 22.

    Houstis N, Rosen ED, Lander ES. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 2006;440:944–8.PubMedCrossrefGoogle Scholar

  • 23.

    Serviddio G, Bellanti F, Vendemiale G. Free radical biology for medicine: learning from nonalcoholic fatty liver disease. Free Radic Biol Med 2013;65:952–68.Web of ScienceCrossrefPubMedGoogle Scholar

  • 24.

    Ashraf NU, Sheikh TA. Endoplasmic reticulum stress and oxidative stress in the pathogenesis of non-alcoholic fatty liver disease. Free Radic Res 2015;49:1405–18.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 25.

    Mormone E, George J, Nieto N. Molecular pathogenesis of hepatic fibrosis and current therapeutic approaches. Chem Biol Interact 2011;193:225–31.Web of ScienceCrossrefPubMedGoogle Scholar

  • 26.

    Başkol M, Dolbun Seçkin K, Başkol G. Advanced oxidation protein products, total thiol levels and total oxidant/antioxidant status in patients with NASH. Turk J Gastroenterol 2014;25(Suppl 1):32–7.Web of SciencePubMedGoogle Scholar

  • 27.

    Leach NV, Dronca E, Vesa SC, Sampelean DP, Craciun EC, Lupsor M, et al. Serum homocysteine levels, oxidative stress and cardiovascular risk in non-alcoholic steatohepatitis. Eur J Intern Med 2014;25:762–7.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 28.

    Jayakumar S, Harrison SA, Loomba R. Noninvasive markers of fibrosis and inflammation in nonalcoholic fatty liver disease. Curr Hepatol Rep 2016;15:86–95.PubMedCrossrefGoogle Scholar

  • 29.

    Feldstein AE, Wieckowska A, Lopez AR, Liu YC, Zein NN, McCullough AJ. Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: a multicenter validation study. Hepatology 2009;50:1072–8.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 30.

    Feldstein AE, Alkhouri N, De Vito R, Alisi A, Lopez R, Nobili V. Serum cytokeratin-18 fragment levels are useful biomarkers for nonalcoholic steatohepatitis in children. Am J Gastroenterol 2013;108:1526–31.CrossrefPubMedWeb of ScienceGoogle Scholar

About the article

Received: 2017-02-27

Accepted: 2017-09-12

Published Online: 2017-11-27

Published in Print: 2018-04-25


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: LaboratoriumsMedizin, Volume 42, Issue 1-2, Pages 31–38, ISSN (Online) 1439-0477, ISSN (Print) 0342-3026, DOI: https://doi.org/10.1515/labmed-2017-0018.

Export Citation

©2018 Walter de Gruyter GmbH, Berlin/Boston.Get Permission

Comments (0)

Please log in or register to comment.
Log in