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.

Targeted Metabolomics Analysis Identifies Intestinal Microbiota-Derived Urinary Biomarkers of Colonization Resistance in Antibiotic-Treated Mice

“…The biomarkers identified are biologically plausible, and our findings for these compounds are consistent with data from previous studies with germfree mice and antibiotic-treated mice or humans (4,9,(15)(16)(17)(18)(19)(20). Cinnamoylglycine is a glycine conjugate of cinnamic acid that was previously shown to be abundant in the serum of conventional mice but present in minimal concentrations in the serum of germfree mice (4).…”

“…Cinnamoylglycine is a glycine conjugate of cinnamic acid that was previously shown to be abundant in the serum of conventional mice but present in minimal concentrations in the serum of germfree mice (4). Cinnamic acid is present in a variety of foods or can be produced from phenylalanine metabolism, and cinnamoylglycine has been shown to be excreted in the urine of mice and humans (16)(17). Dietary tryptophan is metabolized to indole in the colon by tryptophanase produced by enteric bacteria, with subsequent conversion by other bacterial enzymes to indole-3-propionic acid (4).…”

Влияние Формальдегида На Морфогенез Тимуса Белых Крыс

“…Отсутствие существенных изменений относительного веса вилочковой железы (за исключением 6 группы животных) связано с относительно пропорциональным снижением веса органа и веса тела животных. Эти данные согласуются с результатами ранее проведенных исследований влияния ФА на вес тимуса мышей [26] и крыс [3]. Такие изменения, равно как и уменьшение линейных размеров органа, являются типичным следствием воздействия на организм разного рода химических агентов, тем более обладающих цитотоксическими и/или цитостатическими эффектами.…”

Pyrenyl carbon nanostructures for ultrasensitive measurements of formaldehyde in urine

“…5–8 Many techniques have been developed to detect HCHO, including spectrophotometric, 9 electrochemical, 10,11 optical, 12 electronic, 13 and colorimetric 14 methods. Sensitive detection of urine HCHO by chromatography-mass spectrometry methods is known.…”

“…However, these methods involve expensive instrumentation, and time consuming laborious sample preparation, measurement, and analysis steps. 5 In contrast, electrochemical methods are straightforward and cost effective. 15,16 In particular, electrochemical enzymatic amperometric biosensors offer the advantages of direct and quick detection of analytes with simplicity, and by appropriate design of surface strategies, high sensitivity, robustness, and excellent reproducibility can be attained.…”