Identification and Quantification of in Vivo Metabolites of 9,10-Phenanthrenequinone in Human Urine Associated with Producing Reactive Oxygen Species
| Autor: | Yoshito Kumagai, Takayuki Kameda, Ning Tang, Thanyarat Chuesaard, Akira Toriba, Takashi Toyama, Mio Kawai, Kazuichi Hayakawa, Miki Asahi |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Urinary system Metabolite Polycyclic aromatic hydrocarbon Urine Toxicology Tandem mass spectrometry Rats Sprague-Dawley Young Adult chemistry.chemical_compound Tandem Mass Spectrometry In vivo Animals Humans chemistry.chemical_classification Reactive oxygen species Chromatography Molecular Structure Chemistry General Medicine Phenanthrenes Diesel Exhaust Particulate Rats Female Reactive Oxygen Species Chromatography Liquid |
| Zdroj: | Chemical Research in Toxicology. 27:76-85 |
| ISSN: | 1520-5010 0893-228X |
| DOI: | 10.1021/tx400338t |
| Popis: | Polycyclic aromatic hydrocarbon quinones (PAHQs) are components in airborne particulate matter (PM) and generate reactive oxygen species (ROS) in a redox cycling process. 9,10-Phenanthrenequinone (9,10-PQ) is a PAHQ found in diesel exhaust particulates and PM. When inhaled, it produces much more ROS than other PAHQs. We hypothesized that urinary metabolites of 9,10-PQ could serve as biomarkers of PAHQ exposure. Here, we describe methods for pretreating urine samples and analyzing 9,10-PQ metabolites by liquid chromatography with tandem mass spectrometry (LC-MS/MS). In urine from rats intraperitoneally injected with 9,10-PQ, the monoglucuronide of 9,10-dihydroxyphenanthrene (9,10-PQHG) was found to be a major metabolite of 9,10-PQ. 9,10-PQHG was also identified in the urine of a nonoccupationally exposed human by its retention time and MS/MS spectra. Furthermore, the urine contained hardly any free (unmetabolized) 9,10-PQ, but treating it with hydrolytic enzymes released 9,10-PQ from conjugated metabolites such as 9,10-PQHG. The concentrations of 9,10-PQHG in urine samples from nonoccupationally exposed subjects who lived in a suburban area were 2.04-19.08 nmol/mol creatinine. This study is the first to demonstrate the presence of 9,10-PQHG in human urine. Determination of urinary 9,10-PQHG should be useful for determining 9,10-PQ exposure. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|