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2-溴苯酚在雄性斯普拉格-道利大鼠体内的代谢命运及影响。

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

作者信息

Adesina-Georgiadis Kyrillos N, Gray Nicola, Plumb Robert S, Thompson David F, Holmes Elaine, Nicholson Jeremy K, Wilson Ian D

机构信息

Department of Surgery and Cancer Faculty of Medicine, Imperial College London, South Kensington Campus, London, United Kingdom.

Institute of Medical and Biomedical Education, St George's University of London, London, United Kingdom.

出版信息

Xenobiotica. 2019 Nov;49(11):1352-1359. doi: 10.1080/00498254.2018.1559376. Epub 2019 Feb 22.

DOI:10.1080/00498254.2018.1559376
PMID:30557119
Abstract
  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 NMR spectroscopy, inductively coupled plasma (ICP)MS, and UPLC-MS.3. H 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.
摘要
  1. 在雄性斯普拉格-道利大鼠中,腹腔注射0、100或200mg/kg的单剂量溴苯酚(溴苯的一种酚类代谢物)后,对其代谢命运和尿排泄情况进行了研究。

  2. 收集尿液7天,并使用核磁共振氢谱(H NMR)光谱、电感耦合等离子体质谱(ICP)和超高效液相色谱-质谱联用仪(UPLC-MS)对样本进行分析。

  3. 尿液样本的核磁共振氢谱显示,在这些剂量下,溴苯酚对内源性代谢物谱影响很小,这与组织病理学和临床化学数据相符,该研究表明,给予溴苯酚未出现相关变化。

  4. 使用电感耦合等离子体质谱提供了一种选择性检测和定量含溴物质的方法,结果显示,在100mg和200mg剂量组中,在研究的7天内,分别有15%至30%的剂量通过尿液排出。

  5. 含溴物质的排泄在给药后8小时内基本完成。尿液的超高效液相色谱-质谱联用仪分析显示了溴苯酚的多种代谢物,其中溴苯酚葡糖醛酸苷和溴苯酚硫酸盐被确定为主要代谢物。还检测到一些少量的羟基化代谢物,它们以葡糖醛酸苷、硫酸盐或O-甲基共轭物的形式存在。没有证据表明产生了活性代谢物。

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The metabolic fate and effects of 2-Bromophenol in male Sprague-Dawley rats.2-溴苯酚在雄性斯普拉格-道利大鼠体内的代谢命运及影响。
Xenobiotica. 2019 Nov;49(11):1352-1359. doi: 10.1080/00498254.2018.1559376. Epub 2019 Feb 22.
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Identification of 2-bromohydroquinone as a metabolite of bromobenzene and o-bromophenol: implications for bromobenzene-induced nephrotoxicity.
J Pharmacol Exp Ther. 1984 Aug;230(2):360-6.
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Dose-dependent metabolic excretion of bromobenzene and its possible relationship to hepatotoxicity in rats.溴苯在大鼠体内的剂量依赖性代谢排泄及其与肝毒性的可能关系。
J Toxicol Environ Health. 1984;14(2-3):379-91. doi: 10.1080/15287398409530587.
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Nephrotoxicity of phenolic bromobenzene metabolites in the mouse.
Toxicology. 1984 Apr 2;30(3):259-72. doi: 10.1016/0300-483x(84)90097-0.
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Bromobenzene and p-bromophenol toxicity and covalent binding in vivo.溴苯和对溴苯酚在体内的毒性及共价结合
Life Sci. 1982 Mar 8;30(10):841-8. doi: 10.1016/0024-3205(82)90598-7.
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HPLC-NMR with severe column overloading: fast-track metabolite identification in urine and bile samples from rat and dog treated with [14C]-ZD6126.高效液相色谱-核磁共振联用技术用于严重柱超载情况:快速鉴定经[14C]-ZD6126处理的大鼠和犬尿液及胆汁样本中的代谢产物
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The role of 4-bromophenol and 4-bromocatechol in bromobenzene covalent binding and toxicity in isolated rat hepatocytes.
Toxicol Appl Pharmacol. 1985 Jun 30;79(2):323-31. doi: 10.1016/0041-008x(85)90354-0.
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Dihydroxylated mercapturic acid metabolites of bromobenzene.溴苯的二羟基化硫醚氨酸代谢物。
Chem Res Toxicol. 1992 Jul-Aug;5(4):561-7. doi: 10.1021/tx00028a016.
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Bromobenzene metabolism in the rat and guinea pig.
Drug Metab Dispos. 1987 Jan-Feb;15(1):1-11.
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The role of ortho-bromophenol in the nephrotoxicity of bromobenzene in rats.
Toxicol Appl Pharmacol. 1984 Mar 15;72(3):539-49. doi: 10.1016/0041-008x(84)90131-5.

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