title: Increased oxidative/nitrosative stress markers measured non- invasively in patients with high 2,3,7,8-tetrachloro-dibenzo-p-dioxin plasma level.
abstract: OBJECTIVE
  2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) is a highly toxic persistent environmental contaminant, classified as a human carcinogen affecting any target organ. The mechanism of carcinogenesis by TCDD is unclear as TCDD shows a lack of direct genotoxicity. Experimental studies also support the role of oxidative stress in TCDD neurotoxicity and vascular dysfunction. The aim was to investigate markers of oxidative/nitrosative stress and inflammation using non-invasive methods in subjects who got ill due to severe occupational exposure to TCDD in the years 1965-1968.
  
  
  METHODS
  In 11 TCDD-exposed patients, and 16 controls, the analysis of following oxidative products of lipids, proteins and nucleic acids in plasma, urine and exhaled breath condensate (EBC) was performed: 8-iso-prostaglandin F2α (8-isoprostane), 4-hydroxy-trans-2-nonenale (HNE), malondialdehyde (MDA), o-tyrosine (o-Tyr), 8-hydroxyguanosine (8-OHG), 8-hydroxy-2´-deoxy-guanosine (8-OHdG), 5-hydroxymethyluracil (5-OHMeU). In addition, nitric-oxide-tyrosine (NO-Tyr) and leukotriene (LT) B4, C4, D4, and E4 were detected by liquid chromatography-mass spectrometry/mass spectrometry (LC-ESI-MS/MS). TCDD was measured by HRGC/HRMS, body lipid content by densitometry. Single-photon emission spectrometry (SPECT) of the brain was performed and compared with the findings of the patients in 2008.
  
  
  RESULTS
  Mean TCDD plasma level in 2010 was 175 ± 162 pg/g lipids (population level about 2 pg/g), total TCDD content in the body 5.16 ± 4.62 mg. Reduction of cerebral blood flow in SPECT progressed in 8 patients, finding was stable in 2 subjects, and improvement occurred in 1 patient. In the EBC, 10 from 12 markers (all except LT D4 and LT E4), were significantly increased in the patients (p<0.05). In the urine, 7 markers were significantly higher than in the controls (p<0.05): 8-isoprostane, MDA, HNE, LT C4, LT E4, o-Tyr and NO-Tyr. In plasma, only NO-Tyr and 8-OHG were elevated (p<0.05).
  
  
  CONCLUSIONS
  NO-Tyr was increased in all matrices in dioxin-exposed patients. EBC is not limited to lung disorders as the markers of oxidative stress and inflammation were elevated in EBC of patients with normal lung functions. TCDD-induced oxidative stress and inflammation markers can be detected non-invasively in the EBC and urine in the follow-up of the highly-exposed patients. Their prognostic value, however, needs to be elucidated.
authors.affiliation: Department of Occupational Medicine of the First Faculty of Medicine and General University Hospital, Charles University Prague, Czech Republic. daniela.pelclova@LF1.cuni.cz
authors.forename: Daniela
authors.initials: D
authors.lastname: Pelclova
authors.forename: Tomas
authors.initials: T
authors.lastname: Navratil
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Fenclova
authors.forename: Stepanka
authors.initials: S
authors.lastname: Vlckova
authors.forename: Karel
authors.initials: K
authors.lastname: Kupka
authors.forename: Pavel
authors.initials: P
authors.lastname: Urban
authors.forename: Petr
authors.initials: P
authors.lastname: Ridzon
authors.forename: Vit
authors.initials: V
authors.lastname: Zikan
authors.forename: Ludmila
authors.initials: L
authors.lastname: Landova
authors.forename: Kamila
authors.initials: K
authors.lastname: Syslova
authors.forename: Marek
authors.initials: M
authors.lastname: Kuzma
authors.forename: Petr
authors.initials: P
authors.lastname: Kacer
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000032:analysis* / Q000097:blood / Q000652:urine; D001774:Blood Chemical Analysis / Q000379:methods; D016022:Case-Control Studies; D002617:Chemical Industry; D005260:Female; D006540:Herbicides / Q000032:analysis / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000032:analysis; D009994:Osmolar Concentration; D018384:Oxidative Stress / Q000502:physiology*; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood; D026361:Reactive Nitrogen Species / Q000032:analysis* / Q000097:blood / Q000378:metabolism / Q000652:urine; D017382:Reactive Oxygen Species / Q000032:analysis* / Q000097:blood / Q000378:metabolism / Q000652:urine; D015854:Up-Regulation; D016482:Urinalysis / Q000379:methods
chemical_list: D015415:Biomarkers; D006540:Herbicides; D000072317:Polychlorinated Dibenzodioxins; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C445379:1,2,7,8-tetrachlorodibenzo-p-dioxin