title: Small molecule metabolite biomarker candidates in urine from mice exposed to formaldehyde.
abstract: Formaldehyde (FA) is a ubiquitous compound used in a wide variety of industries, and is also a major indoor pollutant emitted from building materials, furniture, etc. Because FA is rapidly metabolized and endogenous to many materials, specific biomarkers for exposure have not been identified. In this study, we identified small metabolite biomarkers in urine that might be related FA exposure. Mice were allowed to inhale FA (0, 4, 8 mg/m3) 6 h per day for 7 consecutive days, and urine samples were collected on the 7th day of exposure. Liquid chromatography coupled with time of flight-mass spectrometry and principal component analysis (PCA) was applied to determine alterations of endogenous metabolites in urine. Additionally, immune toxicity studies were conducted to ensure that any resultant toxic effects could be attributed to inhalation of FA. The results showed a significant decrease in the relative rates of T lymphocyte production in the spleen and thymus of mice exposed to FA. Additionally, decreased superoxide dismutase activity and increased reactive oxygen species levels were found in the isolated spleen cells of exposed mice. A total of 12 small molecules were found to be altered in the urine, and PCA analysis showed that urine from the control and FA exposed groups could be distinguished from each other based on the altered molecules. Hippuric acid and cinnamoylglycine were identified in urine using exact mass and fragment ions. Our results suggest that the pattern of metabolites found in urine is significantly changed following FA inhalation, and hippuric acid and cinnamoylglycine might represent potential biomarker candidates for FA exposure.
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China. 101011288@seu.edu.cn.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China. sunrongli5318@gmail.com.
authors.forename: Rongli
authors.initials: R
authors.lastname: Sun
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China. chenyue_0531@126.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China. kehom123@126.com.
authors.forename: Kehong
authors.initials: K
authors.lastname: Tan
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China. why_314614@163.com.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Wei
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China. lhyin@seu.edu.cn.
authors.forename: Lihong
authors.initials: L
authors.lastname: Yin
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China. yppu@seu.edu.cn.
authors.forename: Yuepu
authors.initials: Y
authors.lastname: Pu
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D015415:Biomarkers / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005557:Formaldehyde / Q000009:adverse effects*; D005998:Glycine / Q000031:analogs & derivatives / Q000652:urine; D006626:Hippurates / Q000652:urine; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008807:Mice, Inbred BALB C; D025341:Principal Component Analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D012130:Respiratory Hypersensitivity; D013154:Spleen / Q000201:enzymology / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D015415:Biomarkers; D006626:Hippurates; D017382:Reactive Oxygen Species; C090448:cinnamoylglycine; D005557:Formaldehyde; D013482:Superoxide Dismutase; C030514:hippuric acid; D005998:Glycine