Protective Effects of Zinc on 2.45 GHz Electromagnetic Radiation-Induced Oxidative Stress and Apoptosis in HEK293 Cells

  • Nural Pastacı ÖzsobacıEmail author
  • Dilek Düzgün Ergün
  • Matem Tunçdemir
  • Derviş Özçelik


Several epidemiological studies have shown that exposure to electromagnetic radiation (EMR) can be harmful to human health. The purpose of this study was to examine oxidative parameters and apoptosis induced by EMR in human kidney embryonic cells (HEK293) and to investigate whether zinc (Zn) has protective effect on EMR-induced apoptosis in HEK293 cells. For our experiment, HEK293 cells were divided into four main groups, control, EMR, 50 μM Zn + EMR, and 100 μM Zn + EMR. HEK293 cells of EMR groups were exposed to 2.45 GHz EMR for 1 h. In Zn groups, HEK293 cells were incubated with different concentrations of Zn for 48 h before EMR exposure. Oxidative stress parameters were determined by spectrophotometric method; bcl-2 and caspase-3 were assessed immunohistochemically and TUNEL method was performed for apoptotic activity. EMR group had higher malondialdehyde (MDA) level and lower superoxide dismutase (SOD) activity compared with control group. In Zn-applied groups, MDA was decreased and SOD activity was increased compared with EMR group. The number of the apoptotic cells and caspase-3 immunopositive cells at EMR group was increased significantly compared with the control group, whereas bcl-2 was decreased. Besides, Zn-treated groups showed a significant reduction in the number of apoptotic cells and caspase-3 from that of EMR group, whereas there was an increase in bcl-2 immunopositivity. Our findings show that EMR caused oxidative stress and apoptotic activation in HEK293 cells. Zn seems to have protective effects on the EMR by increasing SOD activity and bcl-2 immunopositivity, decreasing lipid peroxidation and caspas-3 immunopositivity.


Zinc Electromagnetic radiation Apoptosis Oxidative stress HEK293 


Financial Support

The present work was supported by the Research Fund of Istanbul University (Project No. 51182 and 24619).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Gye M, Park CJ (2012) Effect of electromagnetic field exposure on the reproductive system. Clin Exp Reprod Med 39(1):1–9CrossRefGoogle Scholar
  2. 2.
    Dasdag S, Tas M, Akdag MZ, Yegin K (2015) Effect of long-term exposure of 2.4 GHz radiofrequency radiation emitted from Wi-Fi equipment on testes functions. Electromagn Biol Med 34(1):37–42CrossRefGoogle Scholar
  3. 3.
    Pall ML (2018) Wi-Fi is an important threat to human health. Environ Res 164:405–416CrossRefGoogle Scholar
  4. 4.
    Salaha MB, Abdelmeleka H, Abderraba M (2013) Effects of olive leave extract on metabolic disorders and oxidative stress induced by 2.45GHz WiFi signals. Environ Toxicol Pharmacol 36:826–834CrossRefGoogle Scholar
  5. 5.
    Ozorak A, Naziroglu M, Celik O et al (2013) Wi-Fi (2.45 GHz)- and mobile phone (900 and 1800 MHz)-induced risks on oxidative stress and elements in kidney and testis of rats during pregnancy and the development of offspring. Biol Trace Elem Res Dec 156(1–3):221–229CrossRefGoogle Scholar
  6. 6.
    Guler G, Ozgur E, Keles H et al (2011) Apoptosis resulted from radiofrequency radiation exposure of pregnant rabbits and their infants. Bull Vet Inst Pulawy 55:127–134Google Scholar
  7. 7.
    Achudume A, Onibere B, Aina F, Tchokossa P (2010) Induction of oxidative stress in male rats subchronically exposed to electromagnetic fields at non-thermal intensities. J Electromagn Anal Appl 2:482–487Google Scholar
  8. 8.
    Bediz CS, Baltacı AK, Mogulkoc R et al (2006) Zinc supplementation ameliorates electromagnetic field-induced lipid peroxidation. Tohoku J Exp Med 208:133–140CrossRefGoogle Scholar
  9. 9.
    Oral B, Guney M, Ozguner F, Karahan N, Mungan T, Comlekci S, Cesur G (2006) Endometrial apoptosis induced by a 900-MHz mobile phone: preventive effects of vitamins E and C. Adv Ther 23(6):957–973CrossRefGoogle Scholar
  10. 10.
    Schrantz N, Auffredou M-T, Bourgeade MF et al (2001) Zinc-mediated regulation of caspases activity: dose-dependent inhibition or activation of caspase-3 in human Burkkitt lymphoma B cells (Ramos). Cell Death Differ 8(2):152–161CrossRefGoogle Scholar
  11. 11.
    Faa G, Nurchi VM, Ravarino A (2008) Zinc in gastrointestinal and liver disease. Coordin Chem Rev 252:1257–1269CrossRefGoogle Scholar
  12. 12.
    Saygin M, Caliskan S, Karahan N, Koyu A, Gumral N, Uguz AC (2011) Testicular apoptosis and histopathological changes induced by a 2.45 GHz electromagnetic field. Toxicol Ind Health 27(5):455–463CrossRefGoogle Scholar
  13. 13.
    Lee SR (2018) Critical role of zinc as either an antioxidant or a prooxidant in cellular systems. Oxid Med Cell Longev 20(2018):1–11Google Scholar
  14. 14.
    Aït-Aïssa S, Billaudel B, De Gannes FP et al (2010) In situ detection of gliosis and apoptosis in the brains of young rats exposed in utero to a Wi-Fi signal. Comptes Rendus Physique 11:592–601CrossRefGoogle Scholar
  15. 15.
    Cai L, Iskander S, Cherian MG, Hammond RR (2004) Zinc- or cadmium-pre-induced metallothionein protects human central nervous system cells and astrocytes from radiation-induced apoptosis. Toxicol Lett 146(3):217–226CrossRefGoogle Scholar
  16. 16.
    Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310CrossRefGoogle Scholar
  17. 17.
    Sun Y, Oberley LW, Li Y (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34(3):497–500Google Scholar
  18. 18.
    Khalid M, Mee T, Peyman A, Addison D, Calderon C, Maslanyj M, Mann S (2011) Exposure to radio frequency electromagnetic fields from wireless computer networks: duty factors of Wi-fi devices operating in schools. Prog Biophys Mol Biol 107(3):412–420CrossRefGoogle Scholar
  19. 19.
    Cig B, Nazıroglu M (2015) Investigation of the effects of distance from sources on apoptosis, oxidative stress and cytosolic calcium accumulation via TRPV1 channels induced by mobile phones and Wi-fi in breast cancer cells. Biochim Biophys Acta 1848(10 Pt B):2756–2765CrossRefGoogle Scholar
  20. 20.
    Tang Y, Yang Q, Lu J, Zhang X, Suen D, Tan Y, Jin L, Xiao J, Xie R, Rane M (2010) Zinc supplementation partially prevents renal pathological changes in diabetic rats. J Nutr Biochem 21(3):237–246CrossRefGoogle Scholar
  21. 21.
    Shahin S, Singh VP, Shukla RK, Dhawan A, Gangwar RK, Singh SP, Chaturvedi CM (2013) 2.45 GHz microwave irradiation-induced oxidative stress affects implantation or pregnancy in mice, Mus musculus. Appl Biochem Biotechnol 169(5):1727–1751CrossRefGoogle Scholar
  22. 22.
    Ozguner F, Oktem F, Ayata A, Koyu A, Yilmaz HR (2005) A novel antioxidant agent caffeic acid phenethyl ester prevents long-term mobile phone exposure-induced renal impairment in rat. Mol Cell Biochem 277(1–2):73–80CrossRefGoogle Scholar
  23. 23.
    Merola P, Marino C, Lovisolo GA, Pinto R, Laconi C, Negroni A (2006) Proliferation and apoptosis in a neuroblastoma cell line exposed to 900MHz modulated radiofrequency field. Bioelectromagnetics 27(3):164–171CrossRefGoogle Scholar
  24. 24.
    Esmekaya MA, Seyhan N, Omeroglu S (2010) Pulse modulated 900 MHz radiation induces hypothyroidism and apoptosis in thyroid cells: a light, electron microscopy and immunohistochemical study. Int J Radiat Biol 86(12):1106–1116. CrossRefGoogle Scholar
  25. 25.
    Sunderman FW (1995) The influence of zinc on apoptosis. Ann Clin Lab Sci 25:134–142Google Scholar
  26. 26.
    Nodera M, Yanagisawa H, Wada O (2001) Increased apoptosis in variety of tissues of zinc-deficient rats. Life Sci 69:1639–1649CrossRefGoogle Scholar
  27. 27.
    Truong-Tran AQ, Carter J, Ruffin RE, Zalewski PD (2001) The role of zinc in caspase activation and apoptotic cell death. Bio Metals 14:315–330Google Scholar
  28. 28.
    Thomas DJ, Caffrey TC (1991) Lipopolysaccharide induces doublestranded DNA fragmentation in mouse thymus: protective effect of zinc pre-treatment. Toxicology 68(3):327–337CrossRefGoogle Scholar
  29. 29.
    Matsushita K, Kitagawa K, Matsuyama T (1996) Effect of systemic zinc administration on delayed neuronal death in the gerbil hippocampus. Brain Res 743(1–2):362–365CrossRefGoogle Scholar
  30. 30.
    Meerarani P, Ramadass P, Toborek M, Bauer HC, Bauer H, Hennig B (2000) Zinc protects against apoptosis of endothelial cells induced by linoleic acid and tumor necrosis factor alpha. Am J Clin Nutr 71:81–87CrossRefGoogle Scholar
  31. 31.
    Pourhassanali N, Roshan-Milani S, Kheradmand F, Motazakker M, Bagheri M, Saboory E (2016) Zinc attenuates ethanol-induced Sertoli cell toxicity and apoptosis through caspase-3 mediated pathways. Reprod Toxicol 61:97–103CrossRefGoogle Scholar
  32. 32.
    Zhang D, Li Y, Zhu T, Zhang F, Yang Z, Miao D (2011) Zinc supplementation results in improved therapeutic potential of bone marrow-derived mesenchymal stromal cells in a mouse ischemic limb model. Cytotherapy 13(2):156–164CrossRefGoogle Scholar
  33. 33.
    Smith AF, Longpre J, Loo G (2012) Inhibition by zinc of deoxycholate-induced apoptosis in HCT-116 cells. J Cell Biochem 113(2):650–657CrossRefGoogle Scholar
  34. 34.
    Silva LR, Girard D (2016) Human eosinophils are direct targets to nanoparticles: zinc oxide nanoparticles (ZnO) delay apoptosis and increase the production of the pro-inflammatory cytokines IL-1β and IL-8. Toxicol Lett 259:11–20CrossRefGoogle Scholar
  35. 35.
    Perry DK, Smyth MJ, Stennicke HR, Salvesen GS, Duriez P, Poirier GG, Hannun YA (1997) Zinc is a potent inhibitor of the apoptotic protease, caspase-3. J Biol Chem 272(30):18530–18533CrossRefGoogle Scholar
  36. 36.
    Fukamachi Y, Karasaki Y, Sugiura T (1998) Zinc suppresses apoptosis of U937 cells induced by hydrogen peroxide through an increase of the Bcl-2/Bax ratio. Biochem Biophys Res Commun 246(2):364–369CrossRefGoogle Scholar
  37. 37.
    Susin SA, Daugas E, Ravagnan L, Samejima K, Zamzami N, Loeffler M, Costantini P, Ferri KF, Irinopoulou T, Prévost MC, Brothers G, Mak TW, Penninger J, Earnshaw WC, Kroemer G (2000) Two distinct pathways leading to nuclear apoptosis. J Exp Med 192(4):571–580CrossRefGoogle Scholar
  38. 38.
    Robert E (1999) Intrauterine effects of electromagnetic fields (low frequency, mid-frequency RF, and microwave): review of epidemiologic studies. Teratology 59:292–298CrossRefGoogle Scholar
  39. 39.
    Ulubay M, Yahyazadeh A, Deniz OG, Kıvrak EG, Altunkaynak BZ, Erdem G, Kaplan S (2015) Effects of prenatal 900 MHz electromagnetic field exposures on the histology of rat kidney. Int J Radiat Biol 91(1):35–41CrossRefGoogle Scholar
  40. 40.
    Jin Z, El-Deiry WS (2005) Overview of cell death signaling pathways. Cancer Biol Ther 4:139–163CrossRefGoogle Scholar
  41. 41.
    Erkan E, Garcia CD, Patterson LT, Mishra J, Mitsnefes MM, Kaskel FJ, Devarajan P (2005) Induction of renal tubular cell apoptosis in focal segmental glomerulosclerosis: roles of proteinuria and Fas-dependent pathways. J Am Soc Nephrol 16:398–407CrossRefGoogle Scholar
  42. 42.
    Cachofeiro V, Goicochea M, de Vinuesa SG et al (2008) Oxidative stress and inflammation, a link between chronic kidney disease and cardiovascular disease. Kidney Int Suppl 111:S4–S9CrossRefGoogle Scholar
  43. 43.
    Wu X, Guo R, Chen P, Wang Q, Cunningham PN (2009) TNF induces caspase-dependent inflammation in renal endothelial cells through a rho- and myosin light chain kinasedependent mechanism. Am J Physiol Renal Physiol 297:F316–F326CrossRefGoogle Scholar
  44. 44.
    Lahijani MS, Bigdeli MR, Kalantary S (2011) Effects of sinusoidal electromagnetic fields on histopathology and structures of brains of preincubated white Leghorn chicken embryos. Electromagn Biol Med 30:146–157CrossRefGoogle Scholar
  45. 45.
    Basile A, Zeppa R, Pasquino N, Arra C, Ammirante M, Festa M, Barbieri A, Giudice A, Pascale M, Turco MC, Rosati A (2011) Exposure to 50 MHz electromagnetic field raises the levels of the anti-apoptotic protein BAG3 in melanoma cells. J Cell Physiol 226:2901–2907CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Biophysics Department, Cerrahpasa Medical FacultyIstanbul University-CerrahpasaIstanbulTurkey
  2. 2.Biophysics Department, Faculty of MedicineIstanbul Aydın UniversityIstanbulTurkey
  3. 3.Medical Biology Department, Cerrahpasa Medical FacultyIstanbul University-CerrahpasaIstanbulTurkey

Personalised recommendations