The metabolic fate and effects of 2-Bromophenol in male Sprague-Dawley rats

被引:2
|
作者
Adesina-Georgiadis, Kyrillos N. [1 ,2 ,3 ]
Gray, Nicola [1 ,2 ,4 ]
Plumb, Robert S. [1 ,2 ]
Thompson, David F. [5 ]
Holmes, Elaine [1 ,2 ]
Nicholson, Jeremy K. [1 ,2 ]
Wilson, Ian D. [1 ,2 ]
机构
[1] Imperial Coll London, Dept Surg, South Kensington Campus, London SW7 2AZ, England
[2] Imperial Coll London, Canc Fac Med, South Kensington Campus, London SW7 2AZ, England
[3] St Georges Univ London, Inst Med & Biomed Educ, London, England
[4] Univ Reading, Dept Food & Nutr Sci, Reading RG6 6AP, Berks, England
[5] Univ Keele, Chem & Phys Sci, Keele ST5 5BG, Staffs, England
基金
英国生物技术与生命科学研究理事会;
关键词
2-Bromobenzene; metabolism; nephrotoxicity; metabonomics; ORTHO-BROMOPHENOL; NMR-SPECTROSCOPY; 2-BROMOHYDROQUINONE; BROMOBENZENE;
D O I
10.1080/00498254.2018.1559376
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1. The metabolic fate and urinary excretion of 2-bromophenol, a phenolic metabolite of bromobenzene, was investigated in male Sprague-Dawley rats following single intraperitoneal doses at either 0, 100, or 200 mg/kg. 2. Urine was collected for seven days and samples analysed using H-1 NMR spectroscopy, inductively coupled plasma (ICP)MS, and UPLC-MS. 3. H-1 NMR spectroscopy of the urine samples showed that, at these doses, 2-bromophenol had little effect on endogenous metabolite profiles, supporting histopathology and clinical chemistry data, which showed no changes associated with the administration of 2-bromophenol in this study. 4. The use of ICP-MS provided a means for the selective detection and quantification of bromine-containing species and showed that between 15 and 30% of the dose was excreted via the urine over 7 days of the study for both the 100 and 200 mg doses, respectively. 5. The bulk of the excretion of Br-containing material had occurred by 8 h post administration. UPLC-MS of urine revealed a number of metabolites of 2-bromophenol, with 2-bromophenol glucuronide and 2-bromophenol sulphate identified as the major species. A number of minor hydroxylated metabolites were also detected as their glucuronide, sulphate, or O-methyl conjugates. There was no evidence for the production of reactive metabolites.
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页码:1352 / 1359
页数:8
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