Skip to main content

Advertisement

SpringerLink
Log in

Serum trace elements are associated with hemostasis, lipid spectrum and inflammatory markers in men suffering from acute ischemic stroke

  • Original Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

The primary objective of the study is investigation of the association between trace elements status and hemostasis, lipid spectrum and inflammatory markers in acute ischemic stroke (AIS). A total of 30 men suffering from AIS and 30 healthy controls were involved in the current survey. Blood count, serum lipid spectrum, complement components C4 and C3a, vascular endothelial growth factor (VEGF), S100B protein, NR2 antibodies (NR2Ab), and total antioxidant status (TAS), as well as plasma fibrinogen, and D-dimer levels and activated partial thromboplastin time (APTT) were assessed. Serum trace elements were analyzed using inductively coupled plasma mass spectrometry. AIS patients were characterized by significantly increased fibrinogen, D-dimer, TG, C3a, C4, NR2Ab, and VEGF levels. The leukocyte count, erythrocyte sedimentation rate and serum atherogenic index were also increased in stroke patients. Oppositely, TAS and APTT values, bleeding and blood coagulation time were decreased. AIS patients were characterized by significantly decreased serum Fe and Co concentrations, whereas the level of Cu, I, Li, Mn, Se, Zn, As, Pb, Ni, and especially V and B in serum was significantly increased. Serum V and B tightly correlated with the procoagulant state and inflammatory markers. Multiple regression analysis revealed a significant inverse association between serum Se levels and stroke markers after adjustment for covariates. Therefore, it is hypothesized that elements like vanadium and boron may be closely involved in stroke pathogenesis by modulation of hemostasis and inflammation, whereas the observed increase in Se levels may be considered as a compensatory reaction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abou-Shady EA, Farrag HE, El-Damarawy NA, Mohamed FA, Kamel AM, Massoud AA (1990) In vitro effects of trace elements on blood clotting and platelet function. A-iron, copper, and gold. J Egypt Public Health Ass 66(1–2):21–48

    Google Scholar 

  • Altamura C, Squitti R, Pasqualetti P, Gaudino C, Palazzo P, Tibuzzi F, Lupoi D, Cortezi M, Rossini PM, Vernieri F (2009) Ceruloplasmin/transferrin system is related to clinical status in acute stroke. Stroke 40(4):1282–1288

    Article  CAS  PubMed  Google Scholar 

  • Angelova EA, Atanassova PA, Chalakova NT, Dimitrov BD (2008) Associations between serum selenium and total plasma homocysteine during the acute phase of ischaemic stroke. Eur Neurol 60(6):298–303

    Article  CAS  PubMed  Google Scholar 

  • Assenza G, Zappasodi F, Squitti R, Altamura C, Ventriglia M, Ercolani M, Quattrocchi CC, Lupoi D, Passarelli F, Vernieri F, Rossini PM, Rossini PM (2009) Neuronal functionality assessed by magnetoencephalography is related to oxidative stress system in acute ischemic stroke. NeuroImage 44(4):1267–1273

    Article  PubMed  Google Scholar 

  • Baker SJ, Ding CZ, Akama T, Zhang YK, Hernandez V, Xia Y (2009) Therapeutic potential of boron-containing compounds. Future Med Chem 1(7):1275–1288

    Article  CAS  PubMed  Google Scholar 

  • Barber M, Langhorne P, Rumley A, Lowe GD, Stott DJ (2004) Hemostatic function and progressing ischemic stroke D-dimer predicts early clinical progression. Stroke 35(6):1421–1425

    Article  PubMed  Google Scholar 

  • Bräuer AU, Savaskan NΕ (2004) Molecular actions of selenium in the brain: neuroprotective mechanisms of an essential trace element. Rev Neurosci 15(1):19–32

    Article  PubMed  Google Scholar 

  • Bürgi H (2010) Iodine excess. Best PractRes Cl En 24(1):107–115

    Article  Google Scholar 

  • Cappola AR, Ladenson PW (2003) Hypothyroidism and atherosclerosis. J Clin Endoc Metab 88(6):2438–2444

    Article  CAS  Google Scholar 

  • Carbonell T, Rama R (2007) Iron, oxidative stress and early neurological deterioration in ischemic stroke. Curr Med Chem 14(8):857–874

    Article  CAS  PubMed  Google Scholar 

  • Cavusoglu E, Eng C, Chopra V, Ruwende C, Yanamadala S, Clark LT, Marmur JD (2007) Usefulness of the serum complement component C4 as a predictor of stroke in patients with known or suspected coronary artery disease referred for coronary angiography. Am J Cardiol 100(2):164–168

    Article  CAS  PubMed  Google Scholar 

  • Chamorro A (2004) Role of inflammation in stroke and atherothrombosis. Cerebrovasc Dis 17:1–5

    Article  CAS  Google Scholar 

  • Cherubini A, Ruggiero C, Polidori MC, Mecocci P (2005) Potential markers of oxidative stress in stroke. Free Radical Bio Med 39(7):841–852

    Article  CAS  Google Scholar 

  • Davalos A, Fernandez-Real JM, Ricart W, Soler S, Molins A, Planas E, Genis D (1994) Iron-related damage in acute ischemic stroke. Stroke 25(8):1543–1546

    Article  CAS  PubMed  Google Scholar 

  • Davalos A, Castillo J, Marrugat J, Fernandez-Real JM, Armengou A, Cacabelos P, Rama R (2000) Body iron stores and early neurologic deterioration in acute cerebral infarction. Neurology 54(8):1568–1574

    Article  CAS  PubMed  Google Scholar 

  • Di Carlo A (2009) Human and economic burden of stroke. Age Ageing 38(1):4–5

    Article  PubMed  Google Scholar 

  • Franchini M, Targher G, Montagnana M, Lippi G (2008) Iron and thrombosis. Ann Hematol 87(3):167–173

    Article  CAS  PubMed  Google Scholar 

  • Frederickson CJ, Maret W, Cuajungco MP (2004) Zinc and excitotoxic brain injury: a new model. Neuroscientist 10(1):18–25

    Article  CAS  PubMed  Google Scholar 

  • Frederickson CJ, Giblin LJ, Krężel A et al (2006) Concentrations of extracellular free zinc (pZn) e in the central nervous system during simple anesthetization, ischemia and reperfusion. Exp Neurol 198(2):285–293

    Article  CAS  PubMed  Google Scholar 

  • Garza A, Vega R, Soto E (2006) Cellular mechanisms of lead neurotoxicity. Med Sci Monit 12(3):57–65

    Google Scholar 

  • Go AS, Mozaffarian D, Roger VL, Benjamin EJ et al (2014) Heart disease and stroke statistics-2014 update. Circulation 129(3):28–292

  • González-Villalva A, Rodriguez-Lara A, Montano V, Lima-Melo A, Ramírez G, Fortoul TI (2009) Blood changes generated after vanadium inhalation. Curr Top Toxicol 6:31–38

    Google Scholar 

  • González-Villalva A, Piñón-Zárate G, De la Peña DA et al (2011) The effect of vanadium on platelet function. Environ Toxic Phar 32(3):447–456

    Article  Google Scholar 

  • Hao Z, Wu B, Wang D, Lin S, Tao W, Liu M (2013) A cohort study of patients with anemia on admission and fatality after acute ischemic stroke. J Clin Neurosci 20(1):37–42

    Article  PubMed  Google Scholar 

  • Hartfield DS, Lowry NJ, Keene DL, Yager JY (1997) Iron deficiency: a cause of stroke in infants and children. Pediatr Neurol 16(1):50–53

    Article  CAS  PubMed  Google Scholar 

  • He K, Merchant A, Rimm EB, Rosner BA, Stampfer MJ, Willett WC, Ascherio A (2004) Folate, vitamin B6, and B12 intakes in relation to risk of stroke among men. Stroke 35(1):169–174

    Article  CAS  PubMed  Google Scholar 

  • Huang J, Upadhyay UM, Tamargo RJ (2006) Inflammation in stroke and focal cerebral ischemia. Surg Neurol 66(3):232–245

    Article  PubMed  Google Scholar 

  • Inan Ç, Kilinç K, Kotiloğlu E, Akman HO, Kiliç I, Michl J (1998) Antioxidant therapy of cobalt and vitamin E in hemosiderosis. J Lab Clin Med 132(2):157–165

    Article  CAS  PubMed  Google Scholar 

  • Karadas S, Sayın R, Aslan M et al (2014) Serum levels of trace elements and heavy metals in patients with acute hemorrhagic stroke. J Membrane Biol 247(2):175–180

    Article  CAS  Google Scholar 

  • Klimenko LL, Skalny AV, Turna AA, Tinkov AA, Budanova MN, Baskakov IS, Savostina MS, Mazilina AN, Deev AI, Nikonorov AA (2015) Serum trace element profiles, prolactin, and cortisol in transient ischemic attack patients. Biol Trace Elem Res:1–8

  • Kodali P, Chitta KR, Landero Figueroa JA, Caruso JA, Adeoye O (2012) Detection of metals and metalloproteins in the plasma of stroke patients by mass spectrometry methods. Metallomics 4(10):1077–1087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koh JY, Suh SW, Gwag BJ, He YY (1996) The role of zinc in selective neuronal death after transient global cerebral ischemia. Science 272(5264):1013

    Article  CAS  PubMed  Google Scholar 

  • Kumar V, Gill KD (2009) Aluminium neurotoxicity: neurobehavioural and oxidative aspects. Arch Toxicol 83(11):965–978

    Article  CAS  PubMed  Google Scholar 

  • Lapenna D, Ciofani G, Bruno C, Pierdomenico SD, Giuliani L, Giamberardino MA, Cuccurullo F (2002) Vanadyl as a catalyst of human lipoprotein oxidation. Biochem Pharmacol 63(3):375–380

    Article  CAS  PubMed  Google Scholar 

  • Li YV, Zhang JH (2012) Metal ions in stroke pathophysiology. In: Li YV, Zhang JH (eds) Metal ion in stroke. Springer, New York, pp 1–12

    Chapter  Google Scholar 

  • Lipinski B, Pretorius E (2013) Iron-induced fibrin in cardiovascular disease. Curr Neurovasc Res 10(3):269–274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Z, Li P, Zhao D, Tang H, Guo J (2012) Protection by vanadium, a contemporary treatment approach to both diabetes and focal cerebral ischemia in rats. Biol Trace Elem Res 145(1):66–70

    Article  CAS  PubMed  Google Scholar 

  • Marniemi J, Alanen E, Impivaara O, Seppänen R, Hakala P, Rajala T, Rönnemaa T (2005) Dietary and serum vitamins and minerals as predictors of myocardial infarction and stroke in elderly subjects. Nutr Metab Cardiovasc Dis 15(3):188–197

    Article  PubMed  Google Scholar 

  • Matsuo R, Ago T, Kamouchi M, Kuroda J, Kuwashiro T, Hata J, Kitazono T (2013) Clinical significance of plasma VEGF value in ischemic stroke-research for biomarkers in ischemic stroke (REBIOS) study. BMC Neurol 13(1):32

    Article  PubMed  PubMed Central  Google Scholar 

  • McNicol A, Robertson C, Gerrard JM (1993) Vanadate activates platelets by enhancing arachidonic acid release. Blood 81(9):2329–2338

    CAS  PubMed  Google Scholar 

  • Mehta PJ, Chapman S, Jayam-Trouth A, Kurukumbi M (2012) Acute ischemic stroke secondary to iron deficiency anemia: a case report. Case Rep Neurol Med 2012

  • Mendis S (2013) Stroke disability and rehabilitation of stroke: World Health Organization perspective. Int J Stroke 8(1):3–4

    Article  PubMed  Google Scholar 

  • Millan M, Sobrino T, Castellanos M et al (2007) Increased body iron stores are associated with poor outcome after thrombolytic treatment in acute stroke. Stroke 38(1):90–95

    Article  PubMed  Google Scholar 

  • Millerot-Serrurot E, Bertrand N, Mossiat C et al (2008) Temporal changes in free iron levels after brain ischemia: relevance to the timing of iron chelation therapy in stroke. Neurochem Int 52(8):1442–1448

    Article  CAS  PubMed  Google Scholar 

  • Munshi A, Babu S, Kaul S, Shafi G, Rajeshwar K, Alladi S, Jyothy A (2009) Depletion of serum zinc in ischemic stroke patients. Method Find Exp Clin 32(6):433–436

    Google Scholar 

  • National Institute of Health, National Institute of Neurological Disorders and Stroke (2003) Stroke Scale. www.ninds.nih.gov/doctors/NIH_Stroke_Scale.pdf Last accessed: 25 October, 2016

  • Nielsen FH (2014) Update on human health effects of boron. J Trace Elem Med Bio 28(4):383–387

    Article  CAS  Google Scholar 

  • Olabanji SO, Ige AO, Mazzoli C, Ceccato D, Ajayi EOB, De Poli M, Moschini G (2005) Quantitative elemental analysis of an industrial mineral talc, using accelerator-based analytical technique. Nucl Instrum Methods Phys Res, Sect B 240(1):327–332

    Article  CAS  Google Scholar 

  • Ozcelik D, Uzun H (2009) Copper intoxication; antioxidant defenses and oxidative damage in rat brain. Biol Trace Elem Res 127(1):45–52

    Article  CAS  PubMed  Google Scholar 

  • Penland JG (1998) The importance of boron nutrition for brain and psychological function. BiolTrace Elem Res 66(1–3):299–317

    Article  CAS  Google Scholar 

  • Petrova J, Manolov V, Vasilev V, Tzatchev K, Marinov B (2016) Ischemic stroke, inflammation, iron overload–connection to a hepcidin. Int J Stroke 11(1):16–17

    Article  Google Scholar 

  • Rosamond W, Flegal K, Furie K et al (2008) Heart disease and stroke statistics—2008 update: a report from the American Heart Association statistics committee and stroke statistics subcommittee. Circulation 117:e25–146

    Article  PubMed  Google Scholar 

  • Saenger AK, Christenson RH (2010) Stroke biomarkers: progress and challenges for diagnosis, prognosis, differentiation, and treatment. ClinChem 56(1):21–33

    CAS  Google Scholar 

  • Saito I, Asano T, Sano K, Takakura K, Abe H, Yoshimoto T, Kikuchi H, Ohta T, Ishibashi S (1998) Neuroprotective effect of an antioxidant, ebselen, in patients with delayed neurological deficits after aneurysmal subarachnoid hemorrhage. Neurosurgery 42(2):269–277

    Article  CAS  PubMed  Google Scholar 

  • Salemi G, Gueli MC, D’Amelio M et al (2009) Blood levels of homocysteine, cysteine, glutathione, folic acid, and vitamin B12 in the acute phase of atherothrombotic stroke. Neurol Sci 30(4):361–364

    Article  PubMed  Google Scholar 

  • Sarti C, Rastenyte D, Cepaitis Z, Tuomilehto J (2000) International trends in mortality from stroke, 1968 to 1994. Stroke 31:1588–1501

    Article  CAS  PubMed  Google Scholar 

  • Savaskan NE, Hore N, Eyupoglu IY (2012) Selenium and selenoproteins in neuroprotection and neuronal cell death. In: Li YV, Zhang JH (eds) Metal ion in stroke. Springer, New York, pp 525–536

    Chapter  Google Scholar 

  • Selim MH, Ratan RR (2004) The role of iron neurotoxicity in ischemic stroke. Ageing Res Rev 3(3):345–353

    Article  CAS  PubMed  Google Scholar 

  • Shioda N, Morioka M, Fukunaga K (2008) Vanadium compounds enhance adult neurogenesis after brain ischemia. Yakugakuzasshi: Journal of the Pharmaceutical Society of Japan 128(3):413–417

    CAS  Google Scholar 

  • Shrivastava K, Shukla D, Bansal A, Sairam M, Banerjee PK, Ilavazhagan G (2008) Neuroprotective effect of cobalt chloride on hypobaric hypoxia-induced oxidative stress. Neurochem Int 52(3):368–375

    Article  CAS  PubMed  Google Scholar 

  • Shuttleworth CW, Weiss JH (2011) Zinc: new clues to diverse roles in brain ischemia. Trends Pharmacol Sci 32(8):480–486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silva GS, Koroshetz WJ, González RG, Schwamm LH (2011) Causes of ischemic stroke. In: González RG, Hirsch JA, Lev MH, Schaefer PW, Schwamm LH (eds) Acute ischemic stroke. Springer, Berlin, Heidelberg, pp 25–42

    Chapter  Google Scholar 

  • Singhal AB, Lo EH, Dalkara T, Moskowitz MA (2011) Ischemic stroke: basic pathophysiology and neuroprotective strategies. In: González RG, Hirsch JA, Lev MH, Schaefer PW, Schwamm LH (eds) Acute ischemic stroke. Springer, Berlin, pp 1–24

    Chapter  Google Scholar 

  • Słomka A, Świtońska M, Żekanowska E (2015) Hepcidin levels are increased in patients with acute ischemic stroke: preliminary report. J Stroke Cerebrovasc 24(7):1570–1576

    Article  Google Scholar 

  • Stokowska A, Olsson S, Holmegaard L, Jood K, Blomstrand C, Jern C, Pekna M (2011) Plasma C3 and C3a levels in cryptogenic and large-vessel disease stroke: associations with outcome. Cerebrovasc Dis 32(2):114–122

    Article  PubMed  Google Scholar 

  • Strydom C, Robinson C, Pretorius E, Whitcutt JM, Marx J, Bornman MS (2007) The effect of selected metals on the central metabolic pathways in biology: a review. Water SA 32(4):543–554

    Article  Google Scholar 

  • Subrahmanyam G, Sankar KD, Ramalingam K, Bhanu PS (2013) Hypolipidemic and anti-atherogenic effects of vanadium in high-fat diet rabbits. Trace Elem Electroly 30(3):114–121

    Article  CAS  Google Scholar 

  • Suenaga A, Ueki H (2004) Effect of orthovanadate on platelet aggregation induced by platelet-activating factor. Biol Pharm Bull 27(11):1859–1863

    Article  CAS  PubMed  Google Scholar 

  • Tamer G, Mert M, Tamer I, Mesci B, Kilic D, Arik S (2011) Effects of thyroid autoimmunity on abdominal obesity and hyperlipidaemia. Endokrynol Pol 62(5):421–428

    CAS  PubMed  Google Scholar 

  • Vahidnia A, Van der Voet GB, De Wolff FA (2007) Arsenic neurotoxicity—a review. Hum Exp Toxicol 26(10):823–832

    Article  CAS  PubMed  Google Scholar 

  • Vila N, Castillo J, Dávalos A, Chamorro Á (2000) Proinflammatory cytokines and early neurological worsening in ischemic stroke. Stroke 31(10):2325–2329

    Article  CAS  PubMed  Google Scholar 

  • Vinceti M, Mandrioli J, Borella P, Michalke B, Tsatsakis A, Finkelstein Y (2014) Selenium neurotoxicity in humans: bridging laboratory and epidemiologic studies. Toxicol Lett 230(2):295–303

    Article  CAS  PubMed  Google Scholar 

  • Wallace JMW, Hannon-Fletcher MPA, Robson PJ, Gilmore WS, Hubbard SA, Strain JJ (2002) Boron supplementation and activated factor VII in healthy men. Eur J Clin Nutr 56:1102–1107

    Article  CAS  PubMed  Google Scholar 

  • Wei WQ, Abnet CC, Qiao YL et al (2004) Prospective study of serum selenium concentrations and esophageal and gastric cardia cancer, heart disease, stroke, and total death. Am J ClinNutr 79(1):80–85

    CAS  Google Scholar 

  • Weissman JD, Khunteev GA, Heath R, Dambinova SA (2011) NR2 antibodies: risk assessment of transient ischemic attack (TIA)/stroke in patients with history of isolated and multiple cerebrovascular events. J NeurolSci 300(1):97–102

    CAS  Google Scholar 

  • Yiping T, Yuping W, Jianying C, Zhifeng R (1997) Study on the content of vanadium, molybdenum, barium, aluminium, strontium in serum of sufferers from apoplectic stroke. Trace Elements Science 2:003

    Google Scholar 

  • Young IS, McEneny J (2001) Lipoprotein oxidation and atherosclerosis. Biochem Soc T 29(2):358–362

    Article  CAS  Google Scholar 

  • Yousuf S, Atif F, Ahmad M, Hoda MN, Khan MB, Ishrat T, Islam F (2007) Selenium plays a modulatory role against cerebral ischemia-induced neuronal damage in rat hippocampus. Brain Res 1147:218–225

    Article  CAS  PubMed  Google Scholar 

  • Zwolak I (2014) Vanadium carcinogenic, immunotoxic and neurotoxic effects: a review of in vitro studies. Toxicol Mech Method 24(1):1–12

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. All-Russian Research Institute of Medicinal and Aromatic Plants (VILAR), Moscow, 117216, Russia

    Anatoly V. Skalny

  2. Yaroslavl State University, Yaroslavl, 150000, Russia

    Anatoly V. Skalny & Alexey A. Tinkov

  3. Orenburg State University, Orenburg, 460018, Russia

    Anatoly V. Skalny & Alexey A. Tinkov

  4. RUDN University, Moscow, 117198, Russia

    Anatoly V. Skalny, Margarita G. Skalnaya & Alexey A. Tinkov

  5. Institute of Chemical Physics of N. N. Semenov of the Russian Academy of Sciences, Moscow, 117977, Russia

    Lydmila L. Klimenko, Maria N. Budanova, Ivan S. Baskakov & Anatoly I. Deyev

  6. Institute of Professional Development of Federal Medical-Biological Agency of Russia, 125371, Moscow, Russia

    Aliya A. Turna

  7. Federal Scientific Clinical Centre for Physico-Chemical Medicine of Federal Medical-Biological Agency of Russia, 143000, Odintsovo, Moscow Region, Russia

    Marina S. Savostina & Aksana N. Mazilina

  8. N. I. Pirogov Russian National Research Medical University, 117997, Moscow, Russia

    Anatoly I. Deyev

  9. Orenburg State Medical University, Orenburg, 460000, Russia

    Alexey A. Tinkov

Authors
  1. Anatoly V. Skalny
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lydmila L. Klimenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aliya A. Turna
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria N. Budanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ivan S. Baskakov
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marina S. Savostina
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Aksana N. Mazilina
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Anatoly I. Deyev
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Margarita G. Skalnaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Alexey A. Tinkov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alexey A. Tinkov.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Additional information

Anatoly V. Skalny and Lydmila L. Klimenko contributed equally to the research

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Skalny, A.V., Klimenko, L.L., Turna, A.A. et al. Serum trace elements are associated with hemostasis, lipid spectrum and inflammatory markers in men suffering from acute ischemic stroke. Metab Brain Dis 32, 779–788 (2017). https://doi.org/10.1007/s11011-017-9967-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-017-9967-6

Keywords

Search

Navigation