Phthalate-induced oxidative stress and association with asthma-related airway inflammation in adolescents |
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Authors: | Carmen Franken Nathalie Lambrechts Eva Govarts Gudrun Koppen Elly Den Hond Daniëlla Ooms Stefan Voorspoels Liesbeth Bruckers Ilse Loots Vera Nelen Isabelle Sioen Tim S Nawrot Willy Baeyens Nicolas Van Larebeke Greet Schoeters |
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Institution: | 1. Flemish Institute for Technological Research (VITO), Mol, Belgium;2. Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium;3. Provincial Institute for Hygiene, Antwerp, Belgium;4. Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt University, Hasselt, Belgium;5. Political and Social Sciences, University of Antwerp, Antwerp, Belgium;6. Department of Public Health, Ghent University, Ghent, Belgium;7. Department of Food Safety and Food Quality, Ghent University, Ghent, Belgium;8. Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium;9. Department of Public Health & Primary Care, Leuven University, Leuven, Belgium;10. Department of Analytical and Environmental Chemistry, Vrije Universiteit Brussel, Brussels, Belgium;11. Department of Radiotherapy and Nuclear Medicine, Ghent University, Ghent, Belgium;12. Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark |
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Abstract: | BackgroundIn Belgium, around 8.5% of the children have asthmatic symptoms. Increased asthma risk in children has been reported in relation to exposure to phthalate plasticizers but the underlying mechanisms are largely unknown.AimThe aim of this study was to identify if oxidative stress, assessed by excision of 8-hydroxydeoxyguanosine (8-OHdG) from damaged DNA, is an intermediate marker for the association between phthalate exposure and doctor-diagnosed asthma.Material and methodsIn 418 14–15-year-old youngsters, recruited as a representative sample of residents of Flanders (Belgium), personal exposure to phthalates was assessed by measuring phthalate metabolites in urine: mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-n-butyl phthalate (MnBP), mono-benzyl phthalate (MBzP), mono-isobutyl phthalate (MiBP) and mono-ethyl phthalate (MEP). Analysis of 8-OHdG in urine was used as a sensitive biomarker of oxidative stress at the level of DNA. The presence of doctor-diagnosed asthma was elicited by a self-administered questionnaire. Associations were assessed using multiple linear and logistic regression models. Mediation was tested using Baron and Kenny's regression approach.ResultsA significant increased risk of a youngster being diagnosed with asthma was found for both urinary MnBP (metabolite of dibutyl phthalate (DBP)) and the sum of the three di(2-ethylhexyl) phthalate metabolites (ΣDEHP = MEHP + MEHHP + MEOHP), with respective odds ratio of 1.84 95% CI: 1.02, 3.32] for MnBP and 1.94 95% CI: 1.07, 3.51] for ΣDEHP. In addition, we observed significant associations between all urinary phthalate metabolites and increased urinary levels of 8-OHdG. The associations were stronger in girls than in boys. We did not found evidence that 8-OHdG was associated with doctor-diagnosed asthma.ConclusionThe results of our study are in line with other findings from epidemiological surveys and raise further concern about DEHP and DBP as risk factors for asthma, however, the underlying mechanisms are not yet well understood. |
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Keywords: | 8-OHdG 8-hydroxydeoxyguanosine BBzP butylbenzyl phthalate BMI Body Mass Index CI confidence interval DBP dibutyl phthalate DEHP di(2-ethylhexyl) phthalate DEP diethyl phthalate DIBP diisobutyl phthalate DIDP diisodecyl phthalate DINP diisononyl phthalate DNOP FLEHS Flemish Environment and Health Study HMW high molecular weight IL-1β interleukin β ISAAC International Study of Asthma and Allergy in Childhood LMW low molecular weight LOQ limit of quantification MBzP mono-benzyl phthalate MCNP mono(carboxynonyl) phthalate MCOP mono(carboxyoctyl) phthalate MEHP mono(2-ethylhexyl) phthalate MEHHP mono(2-ethyl-5-hydroxyhexyl) phthalate MEOHP mono(2-ethyl-5-oxohexyl) phthalate MEP mono-ethyl phthalate MiBP mono-isobutyl phthalate MnBP OR odds ratio PPAR peroxisome proliferator-activated receptor ROS reactive oxygen species SG specific gravity Th2 T helper 2-type TNF-α tumor necrosis factor α Human biomonitoring Oxidative stress Phthalate Doctor-diagnosed asthma 8-hydroxydeoxyguanosine |
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