Open Access

Oxidative stress in electrohypersensitivity self‑reporting patients: Results of a prospective in vivo investigation with comprehensive molecular analysis

  • Authors:
    • Philippe Irigaray
    • Daniela Caccamo
    • Dominique Belpomme
  • View Affiliations

  • Published online on: July 12, 2018     https://doi.org/10.3892/ijmm.2018.3774
  • Pages: 1885-1898
  • Copyright: © Irigaray et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

A total of 32 electrohypersensitivity (EHS) self‑reporting patients were serially included in the present prospective study for oxidative stress and antioxidative stress response assessment. All thiobarbituric acid‑reactive substances (TBARs) were measured in the plasma, particularly malondialdehyde (MDA) for lipid peroxidation; additional measurements included total thiol group molecules, reduced glutathione (GSH), oxidized glutathione (GSSG) for oxidative stress assessment and nitrotyrosine, a marker of peroxynitrite‑induced oxidative/nitrosative stress. In addition, the activity of Cu‑Zn superoxide dismutase (SOD1) was measured in red blood cells (RBCs) and glutathione reductase (GR) and glutathione peroxidase (GPx) in RBCs and plasma. Depending of the biomarker considered, 30‑50% of EHS self‑reporting patients presented statistically significantly increased TBARs, MDA, GSSG and NTT mean plasmatic level values in comparison with normal values obtained in healthy controls (P<0.0001). By contrast, there were no plasmatic level values above the upper normal limits for GSH, GSH/GSSG ratio, total glutathione (GluT) and GSH/GluT ratio, and values for these GSH‑associated biomarkers were statistically significantly decreased in 20‑40% of the patients (P<0.0001). Furthermore, in RBCs, mean SOD1 and GPx activities were observed to be statistically significantly increased in ~60% and 19% (P<0.0001) of the patients, respectively, while increased GR activity in RBCs was observed in only 6% of the patients. The present study reports for the first time, to the best of our knowledge, that overall ~80% of EHS self‑reporting patients present with one, two or three detectable oxidative stress biomarkers in their peripheral blood, meaning that these patients‑as is the case for cancer, Alzheimer's disease or other pathological conditions‑present with a true objective new pathological disorder.

References

1 

WHO (World Health Organization): WHO Fact Sheet No. 296. Electromagnetic Fields and Public Health, Electromagnetic Hypersensitivity Electromagnetic Fields and Public Health, Electromagnetic Hypersensitivity. Available from: http://www.who.int/peh-emf/publications/facts/fs296/en/urisimplehttp://www.who.int/peh-emf/publications/facts/fs296/en/. 2005

2 

Hansson Mild K, Repacholi M, van Deventer E and Ravazzani P: Working Group Report. Proceedings International Workshop on EMF hypersensitivity; 25-27 October 2004; Prague, Czech Republic. WHO Press; Milan: pp. 15–26. 2006

3 

Belpomme D, Campagnac C and Irigaray P: Reliable disease biomarkers characterizing and identifying electrohypersensi-tivity and multiple chemical sensitivity as two etiopathogenic aspects of a unique pathological disorder. Rev Environ Health. 30:251–271. 2015. View Article : Google Scholar

4 

Irigaray P, Garrel C, Houssay C, Mantello P and Belpomme D: Beneficial effects of a Fermented Papaya Preparation for the treatment of electrohypersensitivity self-reporting patients: Results of a phase I-II clinical trial with special reference to cerebral pulsation measurement and oxidative stress analysis. Funct Foods Health Dis. 8:122–144. 2018.

5 

Belpomme D, Hardell L, Belyaev I, Burgio E and Carpenter D: Thermal and non-thermal health effects of non-ionizing radiation: An international consensus perspective. Envpol. In press.

6 

Bergqvist U and Vogel E: Possible health implications of subjective symptoms and electromagnetic fields. A report prepared by a European group of experts for the European Commission, DGV. Arbete och Hälsa, European Commission DG V, National Institute for Working Life; 1997, https://gupea.ub.gu.se//bitstream/2077/4156/1/ah1997_19.pdfurisimplehttps://gupea.ub.gu.se//bitstream/2077/4156/1/ah1997_19.pdf.

7 

Santini R, Seigne M, Bonhomme-Faivre L, Bouffet S, Defrasme E and Sage M: Symptoms experienced by users of digital cellular phones: A study of a French engineering school. Electromagn Biol Med. 21:81–88. 2002. View Article : Google Scholar

8 

Röösli M: Radiofrequency electromagnetic field exposure and non-specific symptoms of ill health: A systematic review. Environ Res. 107:277–287. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Baliatsas C, Van Kamp I, Bolte J, Schipper M, Yzermans J and Lebret E: Non-specific physical symptoms and electromagnetic field exposure in the general population: Can we get more specific? A systematic review. Environ Int. 41:15–28. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Hagström M, Auranen J and Ekman R: Electromagnetic hypersensitive Finns: Symptoms, perceived sources and treatments, a questionnaire study. Pathophysiology. 20:117–122. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Irigaray P, Lebar P and Belpomme D: How ultrasonic cerebral tomosphygmography can contribute to the diagnosis of electro-hypersensitivity. JUM. In press.

12 

Greaves MW and Sabroe RA: Histamine: The quintessential mediator. J Dermatol. 23:735–740. 1996. View Article : Google Scholar : PubMed/NCBI

13 

Kapural M, Krizanac-Bengez LJ, Barnett G, Perl J, Masaryk T, Apollo D, Rasmussen P, Mayberg MR and Janigro D: Serum S-100beta as a possible marker of blood-brain barrier disruption. Brain Res. 940:102–104. 2002. View Article : Google Scholar : PubMed/NCBI

14 

Kanner AA, Marchi N, Fazio V, Mayberg MR, Koltz MT, Siomin V, Stevens GH, Masaryk T, Aumayr B, Vogelbaum MA, et al: Serum S100beta: A noninvasive marker of blood-brain barrier function and brain lesions. Cancer. 97:2806–2813. 2003. View Article : Google Scholar : PubMed/NCBI

15 

Morimoto RI: Cells in stress: Transcriptional activation of heat shock genes. Science. 259:1409–1410. 1993. View Article : Google Scholar : PubMed/NCBI

16 

Santoro MG: Heat shock factors and the control of the stress response. Biochem Pharmacol. 59:55–63. 2000. View Article : Google Scholar

17 

Lebel B, Arnoux B, Chanez P, Bougeard YH, Daures JP, Bousquet J and Campbell AM: Ex vivo pharmacologic modulation of basophil histamine release in asthmatic patients. Allergy. 51:394–400. 1996. View Article : Google Scholar : PubMed/NCBI

18 

Smit LH, Korse CM and Bonfrer JM: Comparison of four different assays for determination of serum S-100B. Int J Biol Markers. 20:34–42. 2005. View Article : Google Scholar : PubMed/NCBI

19 

De AK and Roach SE: Detection of the soluble heat shock protein 27 (hsp27) in human serum by an ELISA. J Immunoassay Immunochem. 25:159–170. 2004. View Article : Google Scholar : PubMed/NCBI

20 

Pockley AG, Shepherd J and Corton JM: Detection of heat shock protein 70 (Hsp70) and anti-Hsp70 antibodies in the serum of normal individuals. Immunol Invest. 27:367–377. 1998. View Article : Google Scholar : PubMed/NCBI

21 

Pryor WA: On the detection of lipid hydroperoxides in biological samples. Free Radic Biol Med. 7:177–178. 1989. View Article : Google Scholar : PubMed/NCBI

22 

Sies H: Glutathione and its role in cellular functions. Free Radic Biol Med. 27:916–921. 1999. View Article : Google Scholar : PubMed/NCBI

23 

Radi R: Nitric oxide, oxidants, and protein tyrosine nitration. Proc Natl Acad Sci USA. 101:4003–4008. 2004. View Article : Google Scholar : PubMed/NCBI

24 

Londero D and Lo Greco P: Automated high-performance liquid chromatographic separation with spectrofluorometric detection of a malondialdehyde-thiobarbituric acid adduct in plasma. J Chromatogr A. 729:207–210. 1996. View Article : Google Scholar : PubMed/NCBI

25 

Ohkawa H, Ohishi N and Yagi K: Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 95:351–358. 1979. View Article : Google Scholar : PubMed/NCBI

26 

Akerboom TP and Sies H: Assay of glutathione, glutathione disulfide, and glutathione mixed disulfides in biological samples. Methods Enzymol. 77:373–382. 1981. View Article : Google Scholar : PubMed/NCBI

27 

Ischiropoulos H, Zhu L, Chen J, Tsai M, Martin JC, Smith CD and Beckman JS: Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. Arch Biochem Biophys. 298:431–437. 1992. View Article : Google Scholar : PubMed/NCBI

28 

Jocelyn PC: Spectrophotometric assay of thiols. Methods Enzymol. 143:44–67. 1987. View Article : Google Scholar : PubMed/NCBI

29 

Marklund S and Marklund G: Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem. 47:469–474. 1974. View Article : Google Scholar : PubMed/NCBI

30 

Mannervik B: Measurement of glutathione reductase activity. Curr Protoc Toxicol. May;2001.PubMed/NCBI

31 

Günzler WA, Kremers H and Flohé L: An improved coupled test procedure for glutathione peroxidase (EC 1-11-1-9-) in blood. Z Klin Chem Klin Biochem. 12:444–448. 1974.PubMed/NCBI

32 

Avery SV: Molecular targets of oxidative stress. Biochem J. 434:201–210. 2011. View Article : Google Scholar : PubMed/NCBI

33 

Holmström KM and Finkel T: Cellular mechanisms and physiological consequences of redox-dependent signalling. Nat Rev Mol Cell Biol. 15:411–421. 2014. View Article : Google Scholar : PubMed/NCBI

34 

Cencioni C, Spallotta F, Martelli F, Valente S, Mai A, Zeiher AM and Gaetano C: Oxidative stress and epigenetic regulation in ageing and age-related diseases. Int J Mol Sci. 14:17643–17663. 2013. View Article : Google Scholar : PubMed/NCBI

35 

Belpomme D: Epigenetics and environmental carcinogenesis: Towards a general free radical theory of cancer. In: World Cancer Congress. Session 202: Cancer Epigenetics and DNA Methylation; Abstract no. 1. Barcelona, Spain. pp. 732017

36 

Beckman JS: Oxidative damage and tyrosine nitration from peroxynitrite. Chem Res Toxicol. 9:836–844. 1996. View Article : Google Scholar : PubMed/NCBI

37 

Ray PD, Huang BW and Tsuji Y: Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 24:981–990. 2012. View Article : Google Scholar : PubMed/NCBI

38 

Nielsen F, Mikkelsen BB, Nielsen JB, Andersen HR and Grandjean P: Plasma malondialdehyde as biomarker for oxida-tive stress: Reference interval and effects of life-style factors. Clin Chem. 43:1209–1214. 1997.PubMed/NCBI

39 

Ayala A, Muñoz MF and Argüelles S: Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondi-aldehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev. 2014:3604382014. View Article : Google Scholar

40 

Negre-Salvayre A, Coatrieux C, Ingueneau C and Salvayre R: Advanced lipid peroxidation end products in oxidative damage to proteins. Potential role in diseases and therapeutic prospects for the inhibitors. Br J Pharmacol. 153:6–20. 2008. View Article : Google Scholar

41 

Pizzimenti S, Ciamporcero E, Daga M, Pettazzoni P, Arcaro A, Cetrangolo G, Minelli R, Dianzani C, Lepore A, Gentile F and Barrera G: Interaction of aldehydes derived from lipid peroxidation and membrane proteins. Front Physiol. 4:2422013. View Article : Google Scholar : PubMed/NCBI

42 

Del Rio D, Stewart AJ and Pellegrini N: A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis. 15:316–328. 2005. View Article : Google Scholar : PubMed/NCBI

43 

Slatter DA, Avery NC and Bailey AJ: Identification of a new cross-link and unique histidine adduct from bovine serum albumin incubated with malondialdehyde. J Biol Chem. 279:61–69. 2004. View Article : Google Scholar

44 

Gönenç A, Ozkan Y, Torun M and Simşek B: Plasma malondi-aldehyde (MDA) levels in breast and lung cancer patients. J Clin Pharm Ther. 26:141–144. 2001. View Article : Google Scholar

45 

Akbulut H, Akbulut KG, Icli F and Büyükcelik A: Daily variations of plasma malondialdehyde levels in patients with early breast cancer. Cancer Detect Prev. 27:122–126. 2003. View Article : Google Scholar : PubMed/NCBI

46 

Manju V, Kalaivani Sailaja J and Nalini N: Circulating lipid peroxidation and antioxidant status in cervical cancer patients: A case-control study. Clin Biochem. 35:621–625. 2002. View Article : Google Scholar : PubMed/NCBI

47 

Bakan E, Taysi S, Polat MF, Dalga S, Umudum Z, Bakan N and Gumus M: Nitric oxide levels and lipid peroxidation in plasma of patients with gastric cancer. Jpn J Clin Oncol. 32:162–166. 2002. View Article : Google Scholar : PubMed/NCBI

48 

Dierckx N, Horvath G, van Gils C, Vertommen J, van de Vliet J, De Leeuw I and Manuel-y-Keenoy B: Oxidative stress status in patients with diabetes mellitus: Relationship to diet. Eur J Clin Nutr. 57:999–1008. 2003. View Article : Google Scholar : PubMed/NCBI

49 

Polidori MC, Savino K, Alunni G, Freddio M, Senin U, Sies H, Stahl W and Mecocci P: Plasma lipophilic antioxidants and malo-ndialdehyde in congestive heart failure patients: Relationship to disease severity. Free Radic Biol Med. 32:148–152. 2002. View Article : Google Scholar : PubMed/NCBI

50 

Tamer L, Sucu N, Polat G, Ercan B, Aytacoglu B, Yücebilgiç G, Unlü A, Dikmengil M and Atik U: Decreased serum total antioxidant status and erythrocyte-reduced glutathione levels are associated with increased serum malondialdehyde in atherosclerotic patients. Arch Med Res. 33:257–260. 2002. View Article : Google Scholar : PubMed/NCBI

51 

Delibas N, Ozcankaya R and Altuntas I: Clinical importance of erythrocyte malondialdehyde levels as a marker for cognitive deterioration in patients with dementia of Alzheimer type: A repeated study in 5-year interval. Clin Biochem. 35:137–141. 2002. View Article : Google Scholar : PubMed/NCBI

52 

Logan AC and Wong C: Chronic fatigue syndrome: Oxidative stress and dietary modifications. Altern Med Rev. 6:450–459. 2001.PubMed/NCBI

53 

Manuel y Keenoy B, Moorkens G, Vertommen J and De Leeuw I: Antioxidant status and lipoprotein peroxidation in chronic fatigue syndrome. Life Sci. 68:2037–2049. 2001. View Article : Google Scholar : PubMed/NCBI

54 

Vecchiet J, Cipollone F, Falasca K, Mezzetti A, Pizzigallo E, Bucciarelli T, De Laurentis S, Affaitati G, De Cesare D and Giamberardino MA: Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome. Neurosci Lett. 335:151–154. 2003. View Article : Google Scholar : PubMed/NCBI

55 

Richards RS, Wang L and Jelinek H: Erythrocyte oxidative damage in chronic fatigue syndrome. Arch Med Res. 38:94–98. 2007. View Article : Google Scholar

56 

Maes M: Inflammatory and oxidative and nitrosative stress pathways underpinning chronic fatigue, somatization and psychosomatic symptoms. Curr Opin Psychiatry. 22:75–83. 2009. View Article : Google Scholar : PubMed/NCBI

57 

De Luca C, Thai JC, Raskovic D, Cesareo E, Caccamo D, Trukhanov A and Korkina L: Metabolic and genetic screening of electromagnetic hypersensitive subjects as a feasible tool for diagnostics and intervention. Mediators Inflamm. 2014:9241842014. View Article : Google Scholar : PubMed/NCBI

58 

Aquilano K, Baldelli S and Ciriolo MR: Glutathione: New roles in redox signaling for an old antioxidant. Front Pharmacol. 5:1962014. View Article : Google Scholar : PubMed/NCBI

59 

Zitka O, Skalickova S, Gumulec J, Masarik M, Adam V, Hubalek J, Trnkova L, Kruseova J, Eckschlager T and Kizek R: Redox status expressed as GSH:GSSG ratio as a marker for oxidative stress in paediatric tumour patients. Oncol Lett. 4:1247–1253. 2012. View Article : Google Scholar : PubMed/NCBI

60 

Briviba K, Kissner R, Koppenol WH and Sies H: Kinetic study of the reaction of glutathione peroxidase with peroxynitrite. Chem Res Toxicol. 11:1398–1401. 1998. View Article : Google Scholar : PubMed/NCBI

61 

Rossi L, Squitti R, Pasqualetti P, Marchese E, Cassetta E, Forastiere E, Rotilio G, Rossini PM and Finazzi-Agró A: Red blood cell copper, zinc superoxide dismutase activity is higher in Alzheimer's disease and is decreased by D-penicillamine. Neurosci Lett. 329:137–140. 2002. View Article : Google Scholar : PubMed/NCBI

62 

Pacher P, Beckman JS and Liaudet L: Nitric oxide and peroxyni-trite in health and disease. Physiol Rev. 87:315–424. 2007. View Article : Google Scholar : PubMed/NCBI

63 

O'Donnell VB, Chumley PH, Hogg N, Bloodsworth A, Darley-Usmar VM and Freeman BA: Nitric oxide inhibition of lipid peroxidation: Kinetics of reaction with lipid peroxyl radicals and comparison with alpha-tocopherol. Biochemistry. 36:15216–15223. 1997. View Article : Google Scholar

64 

Ohshima H, Friesen M, Brouet I and Bartsch H: Nitrotyrosine as a new marker for endogenous nitrosation and nitration of proteins. Food Chem Toxicol. 28:647–652. 1990. View Article : Google Scholar : PubMed/NCBI

65 

Ischiropoulos H: Biological tyrosine nitration: A pathophysi-ological function of nitric oxide and reactive oxygen species. Arch Biochem Biophys. 356:1–11. 1998. View Article : Google Scholar : PubMed/NCBI

66 

Schopfer FJ, Baker PR and Freeman BA: NO-dependent protein nitration: A cell signaling event or an oxidative inflammatory response? Trends Biochem Sci. 28:646–654. 2003. View Article : Google Scholar : PubMed/NCBI

67 

Marshall KA, Reist M, Jenner P and Halliwell B: The neuronal toxicity of sulfite plus peroxynitrite is enhanced by glutathione depletion: Implications for Parkinson's disease. Free Radic Biol Med. 27:515–520. 1999. View Article : Google Scholar : PubMed/NCBI

68 

Reynolds MR, Berry RW and Binder LI: Site-specific nitration and oxidative dityrosine bridging of the tau protein by peroxyni-trite: Implications for Alzheimer's disease. Biochemistry. 44:1690–1700. 2005. View Article : Google Scholar : PubMed/NCBI

69 

Vargas MR, Pehar M, Cassina P, Beckman JS and Barbeito L: Increased glutathione biosynthesis by Nrf2 activation in astro-cytes prevents p75NTR-dependent motor neuron apoptosis. J Neurochem. 97:687–696. 2006. View Article : Google Scholar : PubMed/NCBI

70 

Gloire G, Legrand-Poels S and Piette J: NF-kappaB activation by reactive oxygen species: Fifteen years later. Biochem Pharmacol. 72:1493–1505. 2006. View Article : Google Scholar : PubMed/NCBI

71 

Matata BM and Galinanes M: Peroxynitrite is an essential component of cytokines production mechanism in human monocytes through modulation of nuclear factor-kappa B DNA binding activity. J Biol Chem. 277:2330–2335. 2002. View Article : Google Scholar

72 

Falone S, Grossi MR, Cinque B, D'Angelo B, Tettamanti E, Cimini A, Di Ilio C and Amicarelli F: Fifty hertz extremely low-frequency electromagnetic field causes changes in redox and differentiative status in neuroblastoma cells. Int J Biochem Cell Biol. 39:2093–2106. 2007. View Article : Google Scholar : PubMed/NCBI

73 

Park JE, Seo YK, Yoon HH, Kim CW, Park JK and Jeon S: Electromagnetic fields induce neural differentiation of human bone marrow derived mesenchymal stem cells via ROS mediated EGFR activation. Neurochem Int. 62:418–424. 2013. View Article : Google Scholar : PubMed/NCBI

74 

Consales C, Merla C, Marino C and Benassi B: Electromagnetic fields, oxidative stress, and neurodegeneration. Int J Cell Biol. 2012:6838972012. View Article : Google Scholar : PubMed/NCBI

75 

Esmekaya MA, Ozer C and Seyhan N: 900 MHz pulse-modulated radiofrequency radiation induces oxidative stress on heart, lung, testis and liver tissues. Gen Physiol Biophys. 30:84–89. 2011. View Article : Google Scholar : PubMed/NCBI

76 

Kesari KK, Kumar S and Behari J: 900-MHz microwave radiation promotes oxidation in rat brain. Electromagn Biol Med. 30:219–234. 2011. View Article : Google Scholar : PubMed/NCBI

77 

Megha K, Deshmukh PS, Banerjee BD, Tripathi AK, Ahmed R and Abegaonkar MP: Low intensity microwave radiation induced oxidative stress, inflammatory response and DNA damage in rat brain. Neurotoxicology. 51:158–165. 2015. View Article : Google Scholar : PubMed/NCBI

78 

Furtado-Filho OV, Borba JB, Maraschin T, Souza LM, Henriques JA, Moreira JC and Saffi J: Effects of chronic exposure to 950 MHz ultra-high-frequency electromagnetic radiation on reactive oxygen species metabolism in the right and left cerebral cortex of young rats of different ages. Int J Radiat Biol. 91:891–897. 2015. View Article : Google Scholar : PubMed/NCBI

79 

Dasdag S, Akdag MZ, Ulukaya E, Uzunlar AK and Ocak AR: Effect of mobile phone exposure on apoptotic glial cells and status of oxidative stress in rat brain. Electromagn Biol Med. 28:342–354. 2009. View Article : Google Scholar : PubMed/NCBI

80 

Simkó M: Cell type specific redox status is responsible for diverse electromagnetic field effects. Curr Med Chem. 14:1141–1152. 2007. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

October 2018
Volume 42 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Irigaray, P., Caccamo, D., & Belpomme, D. (2018). Oxidative stress in electrohypersensitivity self‑reporting patients: Results of a prospective in vivo investigation with comprehensive molecular analysis. International Journal of Molecular Medicine, 42, 1885-1898. https://doi.org/10.3892/ijmm.2018.3774
MLA
Irigaray, P., Caccamo, D., Belpomme, D."Oxidative stress in electrohypersensitivity self‑reporting patients: Results of a prospective in vivo investigation with comprehensive molecular analysis". International Journal of Molecular Medicine 42.4 (2018): 1885-1898.
Chicago
Irigaray, P., Caccamo, D., Belpomme, D."Oxidative stress in electrohypersensitivity self‑reporting patients: Results of a prospective in vivo investigation with comprehensive molecular analysis". International Journal of Molecular Medicine 42, no. 4 (2018): 1885-1898. https://doi.org/10.3892/ijmm.2018.3774