Acta Neurologica Belgica

, Volume 116, Issue 4, pp 489–494 | Cite as

Dynamic thiol–disulfide homeostasis in acute ischemic stroke patients

  • Hesna Bektas
  • Gonul Vural
  • Sadiye Gumusyayla
  • Orhan Deniz
  • Murat Alisik
  • Ozcan Erel
Original Article

Abstract

Dynamic thiol–disulfide homeostasis plays a critical role in the cellular protection provided by antioxidation. The aim of this study was to investigate whether there is a change in thiol–disulfide homeostasis in acute ischemic stroke patients. Patients diagnosed with acute ischemic stroke that had undergone magnetic resonance diffusion-weighted imaging within the first 24 h were prospectively included in this study. The thiol, disulfide, and total thiol levels were measured during the first 24 and 72 h, and the National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Barthel Index (BI) of the patients were recorded. Overall, the relationships between the thiol–disulfide levels of the patients and the infarct volumes, NIHSS, mRS, and BI scores were investigated. In this study, 54 patients and 53 healthy controls were included. The mean of the native thiol levels in the stroke group was 356.572 ± 61.659 μmol/L (min/max 228.00/546.40), while it was 415.453 ± 39.436 μmol/L (min/max 323.50/488.70) in the control group (p < 0.001). A negative, significant correlation was observed between the infarct volumes and native thiol levels (ρ = −0.378; p = 0.005), and the disulfide levels were similar between the groups (Z = 0.774; p = 0.439). Significant difference was found between the thiol levels of the mild and moderate-severe NIHSS groups (p = 0.026). The changes in the thiol levels under oxidative stress may be associated with the severity of the stroke. Substitution of thiol deficiency and correction of thiol–disulfide imbalance may be beneficial in ischemic stroke.

keywords

Thiol levels Ischemic stroke Infarct volume Disulfide 

Notes

Acknowledgments

The authors state no additional individuals to acknowledge.

Compliance with ethical standards

Funding

This research received no grant from any funding agency in the public, commercial, or non-profit sectors.

Conflict of interest

The authors declare that there are no conflicts of interest.

References

  1. 1.
    Reynolds MA, Kirchick HJ, Dahlen JR, Anderberg JM, McPhersonPH Nakamura KK et al (2003) Early biomarkers of stroke. Clin Chem 49:1733–1739CrossRefPubMedGoogle Scholar
  2. 2.
    Laskowitz DT, Kasner SE, Saver J, Remmel KS, Jauch EC, BRAINStudy Group (2009) Clinical usefulness of a biomarker-based diagnostic test for acute stroke: the Biomarker Rapid Assessment in Ischemic Injury (BRAIN) study. Stroke 40:77–85CrossRefPubMedGoogle Scholar
  3. 3.
    Sharma R, Macy S, Richardson K, Lokhnygina Y, Laskowitz DT (2014) Ablood-based biomarker panel to detect acute stroke. J Stroke Cerebrovasc Dis. 23:910–918CrossRefPubMedGoogle Scholar
  4. 4.
    Matteucci E, Giampietro O (2010) Thiol signalling network with an eye to diabetes. Molecules 15(12):8890–8903. doi: 10.3390/molecules15128890 CrossRefPubMedGoogle Scholar
  5. 5.
    Go YM, Jones DP (2011) Cysteine/cystine redox signaling in cardiovascular disease. Free Radic Biol Med 50(4):495–509. doi: 10.1016/j.freeradbiomed.11.029 CrossRefPubMedGoogle Scholar
  6. 6.
    Prabhu A, Sarcar B, Kahali S, Yuan Z, Johnson JJ, Adam KP, Kensicki E, Chinnaiyan P (2014) Cysteine catabolism: a novel metabolic pathway contributing to glioblastoma growth. Cancer Res 74(3):787–796. doi: 10.1158/0008-5472.CAN-13-1423 CrossRefPubMedGoogle Scholar
  7. 7.
    Tetik S, Ahmad S, Alturfan AA, Fresko I, Disbudak M, Sahin Y, Aksoy H, Yardimci KT (2010) Determination of oxidant stress in plasma of rheumatoid arthritis and primary osteoarthritis patients. Indian J Biochem Biophys 47(6):353–358PubMedGoogle Scholar
  8. 8.
    Rodrigues SD, Batista GB, Ingberman M, Pecoits-Filho R, Nakao LS (2012) Plasma cysteine/cystine reduction potential correlates with plasma creatinine levels in chronic kidney disease. Blood Purif 34(3–4):231–237. doi: 10.1159/000342627 CrossRefPubMedGoogle Scholar
  9. 9.
    Sbrana E, Paladini A, Bramanti E, Spinetti MC, Raspi G (2004) Quantitation of reduced glutathione and cysteine in human immunodeficiency virus-infected patients. Electrophoresis 25(10–11):1522–1529. doi: 10.1002/elps.200305848 CrossRefPubMedGoogle Scholar
  10. 10.
    Calabrese V, Lodi R, Tonon C, D’Agata V, Sapienza M, Scapagnini G, Mangiameli A, Pennisi G, Stella AM, Butterfield DA (2005) Oxidative stress, mitochondrial dysfunction and cellular stress response in Friedreich’s ataxia. J Neurol Sci 233(1–2):145–162. doi: 10.1016/j.jns.2005.03.012 CrossRefPubMedGoogle Scholar
  11. 11.
    Smeyne M, Smeyne RJ (2013) Glutathione metabolism and Parkinson’s disease. Free Radic Biol Med 62:13–25. doi: 10.1016/j.freeradbiomed.2013.05.001 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Steele ML, Fuller S, Maczurek AE, Kersaitis C, Ooi L, Münch G (2013) Chronic inflammation alters production and release of glutathione and related thiols in human U373 astroglial cells. Cell Mol Neurobiol 33(1):19–30. doi: 10.1007/s10571-012-9867-6 CrossRefPubMedGoogle Scholar
  13. 13.
    Kuo LM, Kuo CY, Lin CY, Hung MF, Shen JJ, Hwang TL (2014) Intracellular glutathione depletion by oridonin leads to apoptosis in hepatic stellate cells. Molecules 19(3):3327–3344. doi: 10.3390/molecules19033327 CrossRefPubMedGoogle Scholar
  14. 14.
    Erel O, Neselioglu S (2014) A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem 47:326–332CrossRefPubMedGoogle Scholar
  15. 15.
    Zimmerman RD, Maldjian JA, Brun NC, Horvath B, Skolnick BE (2006) Radiologic estimation of hematoma volume in intracerebral hemorrhage trial by CT scan. AJNR 27:666–670PubMedGoogle Scholar
  16. 16.
    Guzik TJ, Korbut R, Adamek-Guzik T (2003) Nitric oxide and superoxide in inflammation and immune regulation. J Physiol Pharmacol 54(4):469–487PubMedGoogle Scholar
  17. 17.
    Cherubini A, Ruggiero C, Polidori MC, Mecocci P (2005) Potential markers of oxidative stress in stroke. Free Radic Biol Med 39(7):841–852CrossRefPubMedGoogle Scholar
  18. 18.
    Lafon-Cazal M, Pietri S, Culcasi M, Bockaert J (1993) NMDAdependent superoxide production and neurotoxicity. Nature 364(6437):535–537CrossRefPubMedGoogle Scholar
  19. 19.
    Piantadosi CA, Zhang J (1996) Mitochondrial generation of reactive oxygen species after brain ischemia in the rat. Stroke 27(2):327–332CrossRefPubMedGoogle Scholar
  20. 20.
    Lipton SA, Rosenberg PA (1994) Mechanisms of disease: excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med 330(9):613–622CrossRefPubMedGoogle Scholar
  21. 21.
    Walder CE, Green SP, Darbonne WC et al (1997) Ischemic stroke injury is reduced in mice lacking a functional NADPH oxidase. Stroke 28(11):2252–2258CrossRefPubMedGoogle Scholar
  22. 22.
    Matsuo Y, Kihara T, Ikeda M, Ninomiya M, Onodera H, Kogure K (1995) Role of neutrophils in radical production during ischemia and reperfusion of the rat brain: effect of neutrophil depletion on extracellular ascorbyl radical formation. J Cereb Blood Flow Metab 15(6):941–947CrossRefPubMedGoogle Scholar
  23. 23.
    Chan PH (1996) Role of oxidants in ischemic brain damage. Stroke 27(6):1124–1129CrossRefPubMedGoogle Scholar
  24. 24.
    El Kossi MMH, Zakhary MM (2000) Oxidative stress in the context of acute cerebrovascular stroke. Stroke 31(8):1889–1892CrossRefPubMedGoogle Scholar
  25. 25.
    Cherubini A, Ruggiero C, Polidori CM, Mecocci P (2005) Potential markers of oxidative stress in stroke. Free Radic Biol Med 39(7):841–852CrossRefPubMedGoogle Scholar
  26. 26.
    Murakami K, Kondo T, Kawase M, Li Y, Sato S, Chen SF, Chan PH (1998) Mitochondrial susceptibility to oxidative stress exacerbates cerebral infarction that follows permanent focal cerebral ischemia in mutant mice with manganese superoxide dismutase deficiency. J Neurosci 18(1):205–213PubMedGoogle Scholar
  27. 27.
    Fujimura M, Morita-Fujimura Y, Kawase M, Copin JC, Calagui B, Epstein CJ, Chan PH (1999) Manganese superoxide dismutase mediates the early release of mitochondrial cytochrome C and subsequent DNA fragmentation after permanent focal cerebral ischemia in mice. J Neurosci 19(9):3414–3422PubMedGoogle Scholar
  28. 28.
    Gariballa SE, Hutchin TP, Sinclair AJ (2002) Antioxidant capacity after acute ischaemic stroke. QJM 95(10):685–690CrossRefPubMedGoogle Scholar
  29. 29.
    Spranger M, Krempien S, Schwab S, Donneberg S, Hacke W (1997) Superoxide dismutase activity in serum of patients with acute cerebral ischemic injury: correlation with clinical course and infarct size. Stroke 28(12):2425–2428CrossRefPubMedGoogle Scholar
  30. 30.
    Chang C-Y, Lai Y-C, Cheng T-J, Lau M-T, Hu M-L (1998) Plasma levels of antioxidant vitamins, selenium, total sulfhydryl groups and oxidative products in ischemic-stroke patients as compared to matched controls in Taiwan. Free Radic Res 28(1):15–24CrossRefPubMedGoogle Scholar
  31. 31.
    Leppälä JM, Virtamo J, Fogelholm R, Albanes D, Heinonen OP (1999) Different risk factors for different stroke subtypes: association of blood pressure, cholesterol, and antioxidants. Stroke 30(12):2535–2540CrossRefPubMedGoogle Scholar
  32. 32.
    Sen CK, Packer L (2000) Thiol homeostasis and supplements in physical exercise. Am J Clin Nutr 72(2):653–669Google Scholar
  33. 33.
    Turell L, Radi R, Alvarez B (2013) The thiol pool in human plasma: the central contribution of albumin to redox processes. Free Radic Biol Med 65:244–253CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Cremers CM, Jakob U (2013) Oxidant sensing by reversible disulfide bond formation. J Biol Chem 288(37):26489–26496CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Jones DP, Liang Y (2009) Measuring the poise of thiol/disulfide couples in vivo. Free Radic Biol Med 47(10):1329–1338CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Tsai NW, Chang YT, Huang CR, Lin YJ, Lin WC, Cheng BC, Su CM, Chiang YF, Chen SF, Huang CC, Chang WN, Lu CH (2014) Biomed Res Int. 2014:256879. doi: 10.1155/2014/256879 (Epub 2014 May 8) PubMedPubMedCentralGoogle Scholar
  37. 37.
    Leinonen JS, Ahonen JP, Lönnrot K, Jehkonen M, Dastidar PP, Molnár G, Alho H (2000) Low plasma antioxidant activity is associated with high lesion volume and neurological impairment in stroke. Stroke 31(1):33–39CrossRefPubMedGoogle Scholar
  38. 38.
    Musumeci M, Sotgiu S, Persichilli S, Arru G, Angeletti S, Fois ML, Minucci A, Musumeci S (2013) Role of SH levels and markers of immune response in the stroke. Dis Markers 35(3):141–147CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Jeong SO, Pae HO, Oh GS et al (2006) Hydrogen sulfide potentiates interleukin-1 beta induced nitric oxide production via enhancement of extracellular signal-regulated kinase activation in rat vascular smooth muscle cells. Biochem Biophys Res Commun 345(3):938–944CrossRefPubMedGoogle Scholar
  40. 40.
    Yan H, Du J, Tang C (2004) The possible role of hydrogen sulfide on the pathogenesis of spontaneous hypertension in rats. Biochem Biophys Res Commun 313(1):22–27CrossRefPubMedGoogle Scholar
  41. 41.
    Shibuya N, Mikami Y, Kimura Y et al (2009) Vascular endothelium expresses 3-mercaptopyruvate sulfurtransferase and produces hydrogen sulfide. J Biochem 146(5):623–626CrossRefPubMedGoogle Scholar
  42. 42.
    Ozler S, Erel O, Oztas E, Ersoy AO, Ergin M, Sucak A, Neselioglu S, Uygur D, Danisman N (2015) Serum thiol/disulphide homeostasis in preeclampsia. Hypertens Pregnancy 34(4):474–485CrossRefPubMedGoogle Scholar
  43. 43.
    Aruoma OI, Halliwell B, Hoey BM, Butler J (1989) The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. Free Radic Biol Med 6(6):593–597CrossRefPubMedGoogle Scholar

Copyright information

© Belgian Neurological Society 2016

Authors and Affiliations

  • Hesna Bektas
    • 1
  • Gonul Vural
    • 2
  • Sadiye Gumusyayla
    • 2
  • Orhan Deniz
    • 2
  • Murat Alisik
    • 3
  • Ozcan Erel
    • 3
  1. 1.Department of NeurologyAtatürk Training and Research HospitalAnkaraTurkey
  2. 2.Department of NeurologyYildirim Beyazit University Medical SchoolAnkaraTurkey
  3. 3.Department of Clinical BiochemistryYildirim Beyazit University Medical SchoolAnkaraTurkey

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