Biological Trace Element Research

, Volume 189, Issue 1, pp 172–179 | Cite as

Chronic Oral Arsenic Exposure and Its Correlation with Serum S100B Concentration

  • Jafar Golmohammadi
  • Ali Jahanian-Najafabadi
  • Mehdi AliomraniEmail author


Arsenic is one of the most important environmental pollutants especially in drinking water. The S100B protein is presented as a sensitive biomarker for assessment of the blood-brain barrier integrity previously. The objective of this study was to determine the impact of chronic arsenic exposure in drinking water and serum S100B correlation. Fifty-four male BALB/c mice were randomly divided into three groups. Group I and II subjects were treated with arsenic trioxide (1 ppm and 10 ppm, respectively), while the rest received normal drinking water. Arsenic concentration in serum and brain was measured by an atomic absorption spectrometer (Varian model 220-Z) conjugated with a graphite furnace atomizer (GTA-110). Also, a serum S100B protein concentration was determined using commercial ELISA kit during different times of exposure. It was observed that body weight gain was significantly lower from the 10th week onwards in arsenic-treated subjects. However, it did not induce any visible clinical signs of toxicity. Measured arsenic level in serum and brain was higher in espoused groups as compared to the control subjects (p < 0.001 and p < 0.0001, respectively). In addition, serum S100B content was increased over a period of 3 months and had significant differences as compared to the control and 1-ppm group especially after 3 months of exposure in the 10-ppm group (p < 0.0001). In conclusion, it could be inferred that long-term arsenic exposure via drinking water leads to brain arsenic accumulation with serum S100B elevated concentration as a probable BBB disruption consequence.


Arsenic Blood-brain barrier S100B Serum Heavy metals 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Wei B, Yu J, Wang J, Li H, Yang L, Kong C (2017) Trace metals in the urine and hair of a population in an endemic arsenism area. Biol Trace Elem Res:1–8Google Scholar
  2. 2.
    Nriagu JO (1996) A history of global metal pollution. Science 272(5259):223–220CrossRefGoogle Scholar
  3. 3.
    No WFS (2000) Arsenic in drinking waterGoogle Scholar
  4. 4.
    Chakraborti D, Rahman MM, Ahamed S, Dutta RN, Pati S, Mukherjee SC (2016) Arsenic groundwater contamination and its health effects in Patna district (capital of Bihar) in the middle Ganga plain, India. Chemosphere 152:520–529CrossRefGoogle Scholar
  5. 5.
    Kozul CD, Hampton TH, Davey JC, Gosse JA, Nomikos AP, Eisenhauer PL, Weiss DJ, Thorpe JE, Ihnat MA, Hamilton JW (2009) Chronic exposure to arsenic in the drinking water alters the expression of immune response genes in mouse lung. Environ Health Perspect 117(7):1108–1115CrossRefGoogle Scholar
  6. 6.
    Chandravanshi LP, Gupta R, Shukla RK (2018) Developmental neurotoxicity of arsenic: involvement of oxidative stress and mitochondrial functions. Biol Trace Elem Res:1–14Google Scholar
  7. 7.
    Trivedi S, Pandit A, Ganguly G, Das SK (2017) Epidemiology of peripheral neuropathy: an Indian perspective. Ann Indian Acad Neurol 20(3):173–184Google Scholar
  8. 8.
    Niedzwiecki MM, Liu X, Zhu H, Hall MN, Slavkovich V, Ilievski V, Levy D, Siddique AB, Kibriya MG, Parvez F (2018) Serum homocysteine, arsenic methylation, and arsenic-induced skin lesion incidence in Bangladesh: a one-carbon metabolism candidate gene study. Environ Int 113:133–142CrossRefGoogle Scholar
  9. 9.
    Newman JD, Navas-Acien A, Kuo C-C, Guallar E, Howard BV, Fabsitz RR, Devereux RB, Umans JG, Francesconi KA, Goessler W (2016) Peripheral arterial disease and its association with arsenic exposure and metabolism in the Strong Heart Study. Am J Epidemiol:1–12Google Scholar
  10. 10.
    Barchowsky A, States JC (2015) Arsenic-induced cardiovascular disease. Arsenic: exposure sources, health risks, and mechanisms of toxicity:453Google Scholar
  11. 11.
    Cardoso AP, Al-Eryani L (2018) Arsenic-induced carcinogenesis: the impact of miRNA dysregulation. Toxicol SciGoogle Scholar
  12. 12.
    Fry RC (2018) Abstract IA16: Identifying an epigenetic basis for arsenic-associated bladder cancer in a population in Chihuahua Mexico. AACRGoogle Scholar
  13. 13.
    Wang W, Cheng S, Zhang D (2014) Association of inorganic arsenic exposure with liver cancer mortality: a meta-analysis. Environ Res 135:120–125CrossRefGoogle Scholar
  14. 14.
    Smith AH, Hopenhayn-Rich C, Bates MN, Goeden HM, Hertz-Picciotto I, Duggan HM, Wood R, Kosnett MJ, Smith MT (1992) Cancer risks from arsenic in drinking water. Environ Health Perspect 97:259–267CrossRefGoogle Scholar
  15. 15.
    Petty MA, Berryman GE, Jones GH (2018) Arsenic remediation of drinking water using limestoneGoogle Scholar
  16. 16.
    Kayser S, Krzykalla J, Elliott M, Norsworthy K, Gonzales P, Hills R, Baer M, Ráčil Z, Mayer J, Novak J (2017) Characteristics and outcome of patients with therapy-related acute promyelocytic leukemia front-line treated with or without arsenic trioxide. Leukemia 31(11):2347–2354CrossRefGoogle Scholar
  17. 17.
    Song X, Li Y, Liu J, Ji X, Zhao L, Wei Y (2017) Changes in serum adiponectin in mice chronically exposed to inorganic arsenic in drinking water. Biol Trace Elem Res 179(1):140–147CrossRefGoogle Scholar
  18. 18.
    Chaudhuri AN, Basu S, Chattopadhyay S, Gupta SD (1999) Effect of high arsenic content in drinking water on rat brainGoogle Scholar
  19. 19.
    Gharibzadeh S, Hoseini SS (2008) Arsenic exposure may be a risk factor for Alzheimer’s disease. J Neuropsychiatr Clin Neurosci 20(4):501–501CrossRefGoogle Scholar
  20. 20.
    Vahidnia A, Van der Voet G, De Wolff F (2007) Arsenic neurotoxicity—a review. Hum Exp Toxicol 26(10):823–832CrossRefGoogle Scholar
  21. 21.
    Aliomrani M, Sahraian MA, Shirkhanloo H, Sharifzadeh M, Khoshayand MR, Ghahremani MH (2016) Blood concentrations of cadmium and lead in multiple sclerosis patients from Iran. Iran J Pharm Res: IJPR 15(4):825–833Google Scholar
  22. 22.
    Korfias S, Stranjalis G, Papadimitriou A, Psachoulia C, Daskalakis G, Antsaklis A, Sakas D (2006) Serum S-100B protein as a biochemical marker of brain injury: a review of current concepts. Curr Med Chem 13(30):3719–3731CrossRefGoogle Scholar
  23. 23.
    Gahlot G, Soni Y, Joshi G, Saxena R (2017) Clinical significance of serum biomarker S100B to predict outcome after traumatic brain injury. Indian J Mednodent Allied Sci 5(1):24–29CrossRefGoogle Scholar
  24. 24.
    Di Pietro V, Amorini AM, Lazzarino G, Yakoub KM, D’Urso S, Lazzarino G, Belli A (2015) S100B and glial fibrillary acidic protein as indexes to monitor damage severity in an in vitro model of traumatic brain injury. Neurochem Res 40(5):991–999CrossRefGoogle Scholar
  25. 25.
    Barateiro A, Afonso V, Santos G, Cerqueira JJ, Brites D, van Horssen J, Fernandes A (2016) S100B as a potential biomarker and therapeutic target in multiple sclerosis. Mol Neurobiol 53(6):3976–3991CrossRefGoogle Scholar
  26. 26.
    Nandi D, Patra R, Swarup D (2006) Oxidative stress indices and plasma biochemical parameters during oral exposure to arsenic in rats. Food Chem Toxicol 44(9):1579–1584CrossRefGoogle Scholar
  27. 27.
    Aliomrani M, Sahraian MA, Shirkhanloo H, Sharifzadeh M, Khoshayand MR, Ghahremani MH (2017) Correlation between heavy metal exposure and GSTM1 polymorphism in Iranian multiple sclerosis patients. Neurol Sci 38(7):1271–1278CrossRefGoogle Scholar
  28. 28.
    Mukhopadhyay R, Rosen BP, Phung LT, Silver S (2002) Microbial arsenic: from geocycles to genes and enzymes. FEMS Microbiol Rev 26(3):311–325CrossRefGoogle Scholar
  29. 29.
    Hamdi M, Sanchez MA, Beene LC, Liu Q, Landfear SM, Rosen BP, Liu Z (2009) Arsenic transport by zebrafish aquaglyceroporins. BMC Mol Biol 10(1):104CrossRefGoogle Scholar
  30. 30.
    Holson J, Stump D, Clevidence K, Knapp J, Farr C (2000) Evaluation of the prenatal developmental toxicity of orally administered arsenic trioxide in rats. Food Chem Toxicol 38(5):459–466CrossRefGoogle Scholar
  31. 31.
    Mahaffey KR, Fowler BA (1977) Effects of concurrent administration of lead, cadmium, and arsenic in the rat. Environ Health Perspect 19:165–171CrossRefGoogle Scholar
  32. 32.
    Rowland IR, Davies MJ (1982) Reduction and methylation of sodium arsenate in the rat. J Appl Toxicol 2(6):294–299CrossRefGoogle Scholar
  33. 33.
    Hughes MF, Kenyon EM, Edwards BC, Mitchell CT, Del Razo LM, Thomas DJ (2003) Accumulation and metabolism of arsenic in mice after repeated oral administration of arsenate. Toxicol Appl Pharmacol 191(3):202–210CrossRefGoogle Scholar
  34. 34.
    Calatayud M, Barrios JA, Vélez D, Devesa V (2012) In vitro study of transporters involved in intestinal absorption of inorganic arsenic. Chem Res Toxicol 25(2):446–453CrossRefGoogle Scholar
  35. 35.
    Ramírez-Solís A, Mukopadhyay R, Rosen BP, Stemmler TL (2004) Experimental and theoretical characterization of arsenite in water: insights into the coordination environment of As− O. Inorg Chem 43(9):2954–2959CrossRefGoogle Scholar
  36. 36.
    Yang H-C, Fu H-L, Lin Y-F, Rosen BP (2012) Chapter twelve - pathways of arsenic uptake and efflux. In: Argüello JM, Lutsenko S (eds) Current topics in membranes, vol 69. Academic Press, pp 325–358. doi:
  37. 37.
    Liu Z, Sanchez MA, Jiang X, Boles E, Landfear SM, Rosen BP (2006) Mammalian glucose permease GLUT1 facilitates transport of arsenic trioxide and methylarsonous acid. Biochem Biophys Res Commun 351(2):424–430CrossRefGoogle Scholar
  38. 38.
    Prakash C, Soni M, Kumar V (2016) Mitochondrial oxidative stress and dysfunction in arsenic neurotoxicity: a review. J Appl Toxicol 36(2):179–188CrossRefGoogle Scholar
  39. 39.
    Singh V, Kushwaha S, Gera R, Ansari JA, Mishra J, Dewangan J, Patnaik S, Ghosh D (2018) Sneaky entry of IFNγ through arsenic-induced leaky blood–brain barrier reduces CD200 expression by microglial pro-inflammatory cytokine. Molecular Neurobiology:1–12Google Scholar
  40. 40.
    Falcone T, Miniard A, Anand A (2018) F155. Blood brain barrier integrity biomarkers of suicide in adolescents. Biol Psychiatry 83(9):S298CrossRefGoogle Scholar
  41. 41.
    Loftis JM, Valerio J, Taylor J, Huang E, Hudson R, Taylor-Young P, Chang M, Ho SB, Dieperink E, Miranda JL (2018) S100B and inflammatory cytokine levels in blood as potential markers of blood–brain barrier damage and psychiatric impairment in comorbid hepatitis C viral infection and alcohol use disorder. Alcoholism: Clinical and Experimental ResearchGoogle Scholar
  42. 42.
    Rosen BP, Liu Z (2009) Transport pathways for arsenic and selenium: a minireview. Environ Int 35(3):512–515CrossRefGoogle Scholar
  43. 43.
    Kleindienst A, Schmidt C, Parsch H, Emtmann I, Xu Y, Buchfelder M (2010) The passage of S100B from brain to blood is not specifically related to the blood-brain barrier integrity. Cardiovasc Psychiatry Neurol 2010:1–8CrossRefGoogle Scholar
  44. 44.
    Hårdemark H-G, Ericsson N, Kotwica Z, Rundström G, Mendel-Hartvig I, Olsson Y, Påhlman S, Persson L (1989) S-100 protein and neuron-specific enolase in CSF after experimental traumatic or focal ischemic brain damage. J Neurosurg 71(5):727–731CrossRefGoogle Scholar
  45. 45.
    Matsui T, Mori T, Tateishi N, Kagamiishi Y, Satoh S, Katsube N, Morikawa E, Morimoto T, Ikuta F, Asano T (2002) Astrocytic activation and delayed infarct expansion after permanent focal ischemia in rats. Part I: enhanced astrocytic synthesis of S-100β in the periinfarct area precedes delayed infarct expansion. J Cereb Blood Flow Metab 22(6):711–722CrossRefGoogle Scholar
  46. 46.
    Kanner AA, Marchi N, Fazio V, Mayberg MR, Koltz MT, Siomin V, Stevens GH, Masaryk T, Ayumar B, Vogelbaum MA (2003) Serum S100β. Cancer 97(11):2806–2813CrossRefGoogle Scholar
  47. 47.
    Woertgen C, Rothoerl RD, Brawanski A (2001) Neuron-specific enolase serum levels after controlled cortical impact injury in the rat. J Neurotrauma 18(5):569–573CrossRefGoogle Scholar
  48. 48.
    Missler U, Wiesmann M, Friedrich C, Kaps M (1997) S-100 protein and neuron-specific enolase concentrations in blood as indicators of infarction volume and prognosis in acute ischemic stroke. Stroke 28(10):1956–1960CrossRefGoogle Scholar
  49. 49.
    Wunderlich MT, Ebert AD, Kratz T, Goertler M, Jost S, Herrmann M (1999) Early neurobehavioral outcome after stroke is related to release of neurobiochemical markers of brain damage. Stroke 30(6):1190–1195CrossRefGoogle Scholar
  50. 50.
    Tanaka Y, Koizumi C, Marumo T, Omura T, Yoshida S (2007) Serum S100B indicates brain edema formation and predicts long-term neurological outcomes in rat transient middle cerebral artery occlusion model. Brain Res 1137:140–145CrossRefGoogle Scholar
  51. 51.
    Steiner J, Schiltz K, Walter M, Wunderlich MT, Keilhoff G, Brisch R, Bielau H, Bernstein H-G, Bogerts B, Schroeter ML (2010) S100B serum levels are closely correlated with body mass index: an important caveat in neuropsychiatric research. Psychoneuroendocrinology 35(2):321–324CrossRefGoogle Scholar
  52. 52.
    Kim J-H, Byun H-M, Chung E-C, Chung H-Y, Bae O-N (2013) Loss of integrity: impairment of the blood-brain barrier in heavy metal-associated ischemic stroke. Toxicol Res 29(3):157–164CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Pharmacy and Pharmaceutical SciencesIsfahan University of Medical Sciences and Health ServicesIsfahanIran
  2. 2.Department of Pharmaceutical Biotechnology, School of PharmacyIsfahan University of Medical Sciences and Health ServicesIsfahanIran
  3. 3.Department of Toxicology and Pharmacology, School of Pharmacy and Pharmaceutical SciencesIsfahan University of Medical Sciences and Health ServicesIsfahanIran

Personalised recommendations