Hostname: page-component-586b7cd67f-gb8f7 Total loading time: 0 Render date: 2024-11-28T01:18:02.309Z Has data issue: false hasContentIssue false
  • English
  • Français

Determination of dynamic thiol/disulphide homeostasis in children with tetralogy of Fallot and ventricular septal defect

Published online by Cambridge University Press:  01 April 2019

Münevver T. Temel ,
Seniz Demiryürek ,
Ahmet Saracaloglu ,
Celal H. Ozer ,
Hale N. Kahraman ,
Mehmet E. Coskun ,
Osman Başpınar  and
Abdullah T. Demiryürek Open the ORCID record for Abdullah T. Demiryürek [Opens in a new window]
Münevver T. Temel
Affiliation:
Department of Pediatrics, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey
Seniz Demiryürek
Affiliation:
Department of Physiology, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey
Ahmet Saracaloglu
Affiliation:
Department of Medical Pharmacology, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey
Celal H. Ozer
Affiliation:
Department of Pediatrics, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey
Hale N. Kahraman
Affiliation:
Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey
Mehmet E. Coskun
Affiliation:
Department of Pediatrics, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey
Osman Başpınar
Affiliation:
Department of Pediatrics, Division of Pediatric Cardiology, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey
Abdullah T. Demiryürek*
Affiliation:
Department of Medical Pharmacology, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey
*
Author for correspondence: Abdullah T. Demiryürek, PhD, Department of Medical Pharmacology, Faculty of Medicine, University of Gaziantep, Gaziantep 27310, Turkey. Tel: 90-342-3606060 Ext.74355; Fax: 90-342-3601617; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Oxidative stress may contribute to the pathogenesis of congenital heart defects, but the role of dynamic thiol/disulphide homeostasis has not been evaluated. The objective of this study was to assess whether there are changes in thiol/disulphide homeostasis and nitric oxide levels in children with tetralogy of Fallot (TOF) and ventricular septal defect (VSD). A total of 47 children with congenital heart defects (24 TOF and 23 VSD) and 47 healthy age- and sex-matched controls were included in this study. Serum total thiol and native thiol levels were measured using a novel automatic spectrophotometric method. The amount of dynamic disulphide bonds and related ratios were calculated from these values. Serum nitric oxide levels were detected using a chemiluminescence assay. We found that the average native thiol, total thiol, and disulphide levels were decreased in patients with VSD when compared with healthy individuals (p < 0.001, p < 0.001, and p < 0.01, respectively). While native thiol levels were decreased (p < 0.01), disulphide levels were elevated in the TOF group (p < 0.05). We observed marked augmentation of disulphide/native thiol (p < 0.001) and disulphide/total thiol ratios (p < 0.01) in the TOF group. However, there was a significant decrease in native thiol/total thiol ratio in patients with TOF. No significant changes in these ratios were noted in the VSD group. We detected significant elevations in serum nitric oxide levels in children with TOF and VSD (p < 0.001 for all). These results are the first to demonstrate that thiol/disulphide homeostasis and nitric oxide are associated with TOF and VSD in children.

Keywords

Tetralogy of Fallotventricular septal defectthioldisulphideoxidative stress
Type
Original Article
Information
Cardiology in the Young , Volume 29 , Issue 4 , April 2019 , pp. 499 - 504
Copyright
© Cambridge University Press 2019 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Hoffman, JIE. The global burden of congenital heart disease. Cardiovasc J Afr 2013; 24: 141–145.CrossRefGoogle ScholarPubMed
Hoffman, JI, Kaplan, S. The incidence of congenital heart disease. J Am Coll Cardiol 2002; 39: 1890–1900.CrossRefGoogle ScholarPubMed
Pradat, P, Francannet, C, Harris, JA, Robert, E. The epidemiology of cardiovascular defects, part I: a study based on data from three large registries of congenital malformations. Pediatr Cardiol 2003; 24: 195–221.CrossRefGoogle ScholarPubMed
Hoffman, JI, Kaplan, S, Liberthson, RR. Prevalence of congenital heart disease. Am Heart J 2004; 147: 425–439.CrossRefGoogle ScholarPubMed
Marelli, AJ, Mackie, AS, Ionescu-Ittu, R, Rahme, E, Pilote, L. Congenital heart disease in the general population: changing prevalence and age distribution. Circulation 2007; 115: 163–172.CrossRefGoogle ScholarPubMed
Penny, DJ, Vick, GW 3rd. Ventricular septal defect. Lancet 2011; 377: 1103–1112.CrossRefGoogle ScholarPubMed
Rokicki, W, Strzałkowski, A, Kłapcińska, B, Danch, A, Sobczak, A. Antioxidant status in newborns and infants suffering from congenital heart defects. Wiad Lek 2003; 56: 337–340.Google ScholarPubMed
Ercan, S, Cakmak, A, Kösecik, M, Erel, O. The oxidative state of children with cyanotic and acyanotic congenital heart disease. Anadolu Kardiyol Derg 2009; 9: 486–490.Google ScholarPubMed
Pektaş, A, Koca, HB, Pektaş, BM, Köken, R. The oxidative status of children with acyanotic congenital heart diseases: A randomized controlled study. Gazi Med J 2016; 27: 138–141.Google Scholar
Hobbs, CA, Cleves, MA, Zhao, W, Melnyk, S, James, SJ. Congenital heart defects and maternal biomarkers of oxidative stress. Am J Clin Nutr 2005; 82: 598–604.CrossRefGoogle ScholarPubMed
Vidya, G, Suma, HY, Bhat, BV, Gladwin, V, Chand, P. Comparison of DNA damage with the clinical manifestations of children with congenital heart diseases. Curr Pediatr Res 2015; 19: 13–16.Google Scholar
Srujana, K, Begum, SS, Rao, KN, Devi, GS, Jyothy, A, Prasad, MH. Application of the comet assay for assessment of oxidative DNA damage in circulating lymphocytes of Tetralogy of Fallot patients. Mutat Res 2010; 688: 62–65.CrossRefGoogle ScholarPubMed
Erel, O, Neselioglu, S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem 2014; 47: 326–332.CrossRefGoogle ScholarPubMed
Erenler, AK, Yardan, T. Clinical utility of thiol/disulfide homeostasis. Clin Lab 2017; 63: 867–870.CrossRefGoogle ScholarPubMed
Wennmalm, A, Benthin, G, Edlund, A, et al. Metabolism and excretion of nitric oxide in humans. An experimental and clinical study. Circ Res 1993; 73: 1121–1127.CrossRefGoogle ScholarPubMed
Pirinccioglu, AG, Alyan, O, Kizil, G, Kangin, M, Beyazit, N. Evaluation of oxidative stress in children with congenital heart defects. Pediatr Int 2012; 54: 94–98.CrossRefGoogle ScholarPubMed
Hattler, BG, Oddis, CV, Zeevi, A, et al. Regulation of constitutive nitric oxide synthase activity by the human heart. Am J Cardiol 1995; 76: 957–959.CrossRefGoogle ScholarPubMed
Lepic, E, Burger, D, Lu, X, Song, W, Feng, Q. Lack of endothelial nitric oxide synthase decreases cardiomyocyte proliferation and delays cardiac maturation. Am J Physiol Cell Physiol 2006; 291: C1240–C1246.CrossRefGoogle ScholarPubMed
Bloch, W, Fleischmann, BK, Lorke, DE, et al. Nitric oxide synthase expression and role during cardiomyogenesis. Cardiovasc Res 1999; 43: 675–684.CrossRefGoogle ScholarPubMed
Feng, Q, Song, W, Lu, X, et al. Development of heart failure and congenital septal defects in mice lacking endothelial nitric oxide synthase. Circulation 2002; 106: 873–879.CrossRefGoogle ScholarPubMed
Takaya, J, Teraguchi, M, Nogi, S, Ikemoto, Y, Kobayashi, Y. Relation between plasma nitrate and mean pulmonary arterial pressure in ventricular septal defect. Arch Dis Child 1998; 79: 498–501.CrossRefGoogle ScholarPubMed
Gorenflo, M, Zheng, C, Pöge, A, et al. Metabolites of the L-arginine-NO pathway in patients with left-to-right shunt. Clin Lab 2001; 47: 441–447.Google ScholarPubMed
Demiryürek, AT, Cakici, I, Kanzik, I. Peroxynitrite: a putative cytotoxin. Pharmacol Toxicol 1998; 82: 113–117.CrossRefGoogle ScholarPubMed
Ba, LA, Burkholz, T, Schneider, T, Jacob, C. Role of Cysteine. Chapter 10, In: Hughes, AB (ed.), Amino Acids, Peptides and Proteins in Organic Chemistry. Vol.5: Analysis and Function of Amino Acids and Peptides, 1st edn. Wiley-VCH Verlag & Co, Weinheim, Germany, 2012: 361–394.Google Scholar
Vidya, G, Suma, HY, Bhat, BV, Chand, P, Rao, KR. Hypoxia induced DNA damage in children with isolated septal defect and septal defect with great vessel anomaly of heart. J Clin Diagn Res 2014; 8: SC01–SC03.Google Scholar