Monatshefte für Chemie - Chemical Monthly

, Volume 149, Issue 9, pp 1579–1586 | Cite as

Exhaled breath condensate biomarkers reflect systemic changes in patients with chronic dioxin intoxication

  • Daniela PelclovaEmail author
  • Tomas Navratil
  • Stepanka Vlckova
  • Zdenka Fenclova
  • Tomas Pelcl
  • Tereza Kacerova
  • Petr Kacer
Original Paper


2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is highly toxic and affects the cardiovascular system, brain, and skin by AhR-dependent and other mechanisms, as well as causing metabolic impairments and cancer. The involvement of the respiratory system has not yet been studied. TCDD in the blood was measured and biomarkers of oxidative stress and inflammation were analysed in 2016 in the exhaled breath condensate (EBC) of the last eight male survivors (mean age 72.4 ± 1.3 years) from 80 workers intoxicated with TCDD during the production of herbicides from 1965 to 1968. The results were compared with their findings in 2010 to evaluate a trend. Malondialdehyde, 4-hydroxy-trans-nonenale, and 8-isoprostaglandin F2α (8-isoprostane), in addition to markers of the oxidation of nucleic acids and proteins 8-hydroxy-2-deoxyguanosine, 8-hydroxyguanosine, 5-(hydroxymethyl)uracil, o-tyrosine, and 3-nitrotyrosine, as well as markers of inflammation leukotrienes and anti-inflammatory lipoxins, were analysed in EBC by liquid chromatography–electrospray ionisation–tandem mass spectrometry. In addition, the patients underwent chest X-ray, spirometry and fractional exhaled nitric oxide (FeNO) examinations. The control group included 7 men (66 ± 16 years) with comparable lifestyle factors. The median plasma TCDD level lowered from 155 (28–553) ng/kg fat in 2010 to 112 (46–390) ng/kg fat in 2016, i.e., 50 years after exposure. The mean TCDD body deposit was 5.0 ± 3.7 µg. Serum TCDD level in the pooled sample of the controls was 12 ng/kg fat. All markers of oxidative stress, LTB4 and LTC4, remained overexpressed in patients and anti-inflammatory lipoxins were under-expressed compared to controls (all p < 0.01). The mean FeNO and spirometry results were within the reference values. Borderline X-ray findings and combined lung function impairments were seen in the patients with the lower TCDD plasma levels. Differences in the expression of the biomolecular markers in EBC as compared to controls were not associated with lung impairments and the respiratory parameters measured. Therefore, these EBC markers can be used to evaluate systemic oxidative stress and inflammation in tissues and the endovascular, atherosclerotic, neurotoxic, and metabolic effects of TCDD.

Graphical abstract


TCDD Oxidative stress Leukotrienes Lipoxins Occupational intoxication 



This work was partially funded by projects PROGRES Q25/LF1, Q29/LF1 of the Charles University and 43/17/RPZP of the Ministry of Health.


  1. 1.
    Cerna M, Kratenova J, Zejglicova K, Brabec M, Maly M, Smid J, Crhova S, Grabic R, Volf J (2007) Chemosphere 67:S238CrossRefPubMedGoogle Scholar
  2. 2.
    Iszatt N, Stigum H, Govarts E, Murinova LP, Schoeters G, Trnovec T, Legler J, Thomsen C, Koppen G, Eggesbo M (2016) Environ Int 94:399CrossRefPubMedGoogle Scholar
  3. 3.
    Trnovec T, Jusko TA, Sovcikova E, Lancz K, Chovancova J, Patayova H, Palkovicova L, Drobna B, Langer P, Van den Berg M, Dedik L, Wimmerova S (2013) Environ Health Perspect 121:886CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Saurat JH, Kaya G, Saxer-Sekulic N, Pardo B, Becker M, Fontao L, Mottu F, Carraux P, Pham XC, Barde C, Fontao F, Zennegg M, Schmid P, Schaad O, Descombes P, Sorg O (2012) Toxicol Sci 125:310CrossRefPubMedGoogle Scholar
  5. 5.
    Hwang HJ, Dornbos P, Steidemann M, Dunivin TK, Rizzo M, LaPres JJ (2016) Toxicol Appl Pharmacol 304:121CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    IARC (1997) Polychlorinated dibenzo-para-dioxins and polychlorinated dibenzofurans. IARC Monogr Eval Carcinog Risks Hum 69:227Google Scholar
  7. 7.
    Dziubanek G, Marchwinska E, Hajok I, Piekut A (2016) Cent Eur J Public Health 24:115CrossRefPubMedGoogle Scholar
  8. 8.
    Pelclova D, Fenclova Z, Dlaskova Z, Urban P, Lukas E, Prochazka B, Rappe C, Preiss J, Kocan A, Vejlupkova J (2001) Arch Environ Health 56:493CrossRefPubMedGoogle Scholar
  9. 9.
    Landi MT, Bertazzi PA, Baccarelli A, Consonni D, Masten S, Lucier G, Mocarelli P, Needham L, Caporaso N, Grassman J (2003) Carcinogenesis 24:673CrossRefPubMedGoogle Scholar
  10. 10.
    Pelclova D, Urban P, Preiss J, Lukas E, Fenclova Z, Navratil T, Dubska Z, Senholdova Z (2006) Rev Environ Health 21:119CrossRefPubMedGoogle Scholar
  11. 11.
    Manh HD, Kido T, Okamoto R, Sun XL, Anh LT, Supratman S, Maruzeni S, Nishijo M, Nakagawa H, Honma S, Nakano T, Takasuga T, Nhu DD, Hung NN, Son LK (2014) Environ Sci Technol 48:3496CrossRefPubMedGoogle Scholar
  12. 12.
    Jeanneret F, Boccard J, Badoud F, Sorg O, Tonoli D, Pelclova D, Vlckova S, Rutledge DN, Samer CF, Hochstrasser D, Saurat JH, Rudaz S (2014) Toxicol Lett 230:234CrossRefPubMedGoogle Scholar
  13. 13.
    Pelclova D, Urban P, Fenclova Z, Vlckova S, Ridzon P, Kupka K, Meckova Z, Bezdicek O, Navratil T, Rosmus J, Zakharov S (2018) Basic Clin Pharmacol Toxicol 122:271CrossRefPubMedGoogle Scholar
  14. 14.
    Neuberger M, Rappe C, Bergek S, Cai H, Hansson M, Jager R, Kundi M, Lim CK, Wingfors H, Smith AG (1999) Environ Res 81:206CrossRefPubMedGoogle Scholar
  15. 15.
    Pelclova D, Fenclova Z, Preiss J, Prochazka B, Spacil J, Dubska Z, Okrouhlik B, Lukas E, Urban P (2002) Int Arch Occup Environ Health 75(Suppl):S60PubMedGoogle Scholar
  16. 16.
    Pelclova D, Prazny M, Skrha J, Fenclova Z, Kalousova M, Urban P, Navratil T, Senholdova Z, Smerhovsky Z (2007) Hum Exp Toxicol 26:705CrossRefPubMedGoogle Scholar
  17. 17.
    Urban P, Pelclova D, Lukas E, Kupka K, Preiss J, Fenclova Z, Smerhovsky Z (2007) Eur J Neurol 14:213CrossRefPubMedGoogle Scholar
  18. 18.
    Pelclova D, Fenclova Z, Urban P, Ridzon P, Preiss J, Kupka K, Malik J, Dubska Z, Navratil T (2009) Neuro Endocrinol Lett 30:219PubMedGoogle Scholar
  19. 19.
    Sorg O (2014) Toxicol Lett 230:225CrossRefPubMedGoogle Scholar
  20. 20.
    Peters-Golden M (2008) Curr Allergy Asthma Rep 8:367CrossRefPubMedGoogle Scholar
  21. 21.
    Pelclova D, Fenclova Z, Vlckova S, Lebedova J, Syslova K, Pecha O, Belacek J, Navratil T, Kuzma M, Kacer P (2012) Ind Health 50:299CrossRefPubMedGoogle Scholar
  22. 22.
    Pelclova D, Fenclova Z, Vlckova S, Klusackova P, Lebedova J, Syslova K, Belacek J, Kuzma M, Navratil T, Zakharov S, Kacer P (2014) Int J Occup Med Environ Health 27:206CrossRefPubMedGoogle Scholar
  23. 23.
    Antus B (2016) Oxid Med Cell Longev 2016:2930434CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Pelclova D, Fenclova Z, Kacer P, Kuzma M, Navratil T, Lebedova J (2008) Ind Health 46:484CrossRefPubMedGoogle Scholar
  25. 25.
    Pelclova D, Fenclova Z, Kacer P, Navratil T, Kuzma M, Lebedova J, Klusackova P (2007) Ind Health 45:766CrossRefPubMedGoogle Scholar
  26. 26.
    Chandrasekharan JA, Sharma-Walia N (2015) J Inflammation Res 8:181Google Scholar
  27. 27.
    Duvall MG, Bruggemann TR, Levy BD (2017) Mol Aspects Med 58:44CrossRefPubMedGoogle Scholar
  28. 28.
    Pelclova D, Navratil T, Fenclova Z, Vlckova S, Kupka K, Urban P, Ridzon P, Zikan V, Landova L, Syslova K, Kuzma M, Kacer P (2011) Neuro Endocrinol Lett 32:71PubMedGoogle Scholar
  29. 29.
    Van den Berg M, Birnbaum LS, Denison M, De Vito M, Farland W, Feeley M, Fiedler H, Hakansson H, Hanberg A, Haws L, Rose M, Safe S, Schrenk D, Tohyama C, Tritscher A, Tuomisto J, Tysklind M, Walker N, Peterson RE (2006) Toxicol Sci 93:223CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Cerna M, Bajgar L, Crhova S, Grabic R, Kozak J, Kratenova J, Maly M, Volf M, Smid J, Zejglicova K (2004) Organohalogen Compd 66:3637Google Scholar
  31. 31.
    Toren K, Murgia N, Schioler L, Bake B, Olin AC (2017) BMC Pulm Med 17:118CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Syslova K, Bohmova A, Demirbag E, Simkova K, Kuzma M, Pelclova D, Sedlak V, Cap P, Martasek P, Kacer P (2013) J Pharm Biomed Anal 81–82:108CrossRefPubMedGoogle Scholar
  33. 33.
    Pelcl T, Skrha J, Prazny M, Vlckova S, Fenclova Z, Navratil T, Malik J, Diblik P, Zikan V, Pelclova D (2018) Basic Clin Pharmacol Toxicol. CrossRefPubMedGoogle Scholar
  34. 34.
    Syslova K, Bohmova A, Mikoska M, Kuzma M, Pelclova D, Kacer P (2014) Oxid Med Cell Longev 562860Google Scholar
  35. 35.
    Go YM, Jones DP (2017) Clin Sci 131:1669CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Mastalerz-Migas A, Reksa D, Pokorski M, Steciwko A, Muszynska A, Bunio A, Drobnik J, Pokorna-Kalwak D (2007) J Physiol Pharmacol 58:363PubMedGoogle Scholar
  37. 37.
    Ahmadzai H, Huang SY, Hettiarachchi R, Lin JL, Thomas PS, Zhang Q (2013) Clin Chem Lab Med 51:1343CrossRefPubMedGoogle Scholar
  38. 38.
    Ho E, Galougahi KK, Liu CC, Bhindi R, Figtree GA (2013) Redox Biol 1:483CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Swardfager W, Yu D, Scola G, Cogo-Moreira H, Chan P, Zou Y, Herrmann N, Lanctot KL, Ramirez J, Gao FQ, Masellis M, Swartz RH, Sahlas DJ, Chan PC, Ojeda-Lopez C, Milan-Tomas A, Pettersen JA, Andreazza AC, Black SE (2017) Neurobiol Aging 59:91CrossRefPubMedGoogle Scholar
  40. 40.
    Saeki K, Yokomizo T (2017) Semin Immunol 33:30CrossRefPubMedGoogle Scholar
  41. 41.
    Gelfand EW (2017) Semin Immunol 33:44CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Yokomizo T (2015) J Biochem (Tokyo) 157:65CrossRefGoogle Scholar
  43. 43.
    Sun M, Wang R, Han QH (2017) Scientific Rep 7:44352CrossRefGoogle Scholar
  44. 44.
    Markar SR, Wiggins T, Kumar S, Hanna GB (2015) J Clin Gastroenterol 49:1CrossRefPubMedGoogle Scholar
  45. 45.
    Takeda T, Komiya Y, Koga T, Ishida T, Ishii Y, Kikuta Y, Nakaya M, Kurose H, Yokomizo T, Shimizu T, Uchi H, Furue M, Yamada H (2017) J Biol Chem 292:10586CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Seok SH, Lee W, Jiang L, Molugu K, Zheng AP, Li YT, Park S, Bradfield CA, Xing YN (2017) Proc Natl Acad Sci USA 114:5431CrossRefPubMedGoogle Scholar
  47. 47.
    Horvath I, Barnes PJ, Loukides S, Sterk PJ, Hogman M, Olin AC, Amann A, Antus B, Baraldi E, Bikov A, Boots AW, Bos LD, Brinkman P, Bucca C, Carpagnano GE, Corradi M, Cristescu S, de Jongste JC, Dinh-Xuan AT, Dompeling E, Fens N, Fowler S, Hohlfeld JM, Holz O, Jobsis Q, Van De Kant KV, Knobel HH, Kostikas K, Lehtimaki L, Lundberg J, Montuschi P, Van Muylem A, Pennazza G, Reinhold P, Ricciardolo FLM, Rosias P, Santonico M, van der Schee MP, van Schooten FJ, Spanevello A, Tonia T, Vink TJ (2017) Eur Resp J 49:1600965CrossRefGoogle Scholar
  48. 48.
    Syslova K, Kacer P, Kuzma M, Pankracova A, Fenclova Z, Vlckova S, Lebedova J, Pelclova D (2010) J Breath Res 4:017104CrossRefPubMedGoogle Scholar
  49. 49.
    Neprasova M, Maixnerova D, Novak J, Reily C, Julian BA, Boron J, Novotny P, Suchanek M, Tesar V, Kacer P (2016) Dis Markers 2016:3650909CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Syslova K, Kacer P, Vilhanova B, Kuzma M, Lipovova P, Fenclova Z, Lebedova J, Pelclova D (2011) J Chromatogr B 879:2220CrossRefGoogle Scholar
  51. 51.
    Effros RM, Peterson B, Casaburi R, Su J, Dunning M, Torday J, Biller J, Shaker R (2005) J Appl Physiol 99:1286CrossRefPubMedGoogle Scholar
  52. 52.
    Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CPM, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J (2005) Eur Resp J 26:319CrossRefGoogle Scholar
  53. 53.
    Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, Olin AC, Plummer AL, Taylor DR (2011) Am J Respir Crit Care Med 184:602CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    American Thoracic Society and European Respiratory Society (2005) Am J Respir Crit Care Med 171:912CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Occupational Medicine, First Faculty of MedicineCharles University and General University Hospital in PraguePrague 2Czech Republic
  2. 2.J. Heyrovsky Institute of Physical Chemistry of the Czech Academy of SciencesPrague 8Czech Republic
  3. 3.3rd Medical Department, First Faculty of MedicineCharles University and General University Hospital in PraguePrague 2Czech Republic
  4. 4.First Faculty of MedicineBiocev, Charles UniversityVestecCzech Republic

Personalised recommendations