Biomarkers of neurotoxic shellfish poisoning

Biomarkers of neurotoxic shellfish poisoning
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DOI:
10.1016/j.toxicon.2008.04.175
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发表时间:
2008-08-01
期刊:
影响因子:
2.8
通讯作者:
Dickey, Robert W.
Dickey, Robert W.
中科院分区:
医学4区
文献类型:
--
作者:
Abraham, Ann;Plakas, Steven M.;Dickey, Robert W.

文献摘要

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从诊断为神经毒性贝类中毒(NSP)患者的尿液标本进行了检查短尾寒螺毒素中毒的生物标志物。采用固相萃取(SPE)富集尿液中的短杆菌毒素,并采用酶联免疫吸附试验(ELISA)和液相色谱-串联质谱(LC-MS/MS)进行分析。通过LC对尿液提取物进行分级,并通过ELISA分析各级分中的短毒素。在随后的LC-MS/MS分析中,鉴定了B型骨架的几种短尾寒毒代谢物,洗脱曲线与ELISA的洗脱曲线一致。尿液中更丰富的短尾轮虫毒素代谢物的结构特征通过LC-MS/MS。除BTX-3外,尿液中的短尾轮虫毒素代谢物与贝类和贝类粉残留物中发现的不同。这些主要尿液代谢物的拟定结构为甲硫基BTX-3、27-环氧BTX-3和还原BTX-B5。BTX-3在所有检查的标本中均被发现。通过LC-MS/MS测定的尿中BTX-3浓度与通过ELISA测定的复合毒素测量值良好相关(r(2)= 0.96)。BTX-3是一个有用的生物标志物,用于确认NSP的临床诊断。爱思唯尔有限公司出版
Urine specimens from patients diagnosed with neurotoxic shellfish poisoning (NSP) were examined for biomarkers of brevetoxin intoxication. Brevetoxins were concentrated from urine by using solid-phase extraction (SPE), and analyzed by enzyme-linked immunosorbent assay (ELISA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Urine extracts were fractionated by LC, and fractions analyzed for brevetoxins by ELISA. In subsequent LC-MS/MS analyses, several brevetoxin metabolites of B-type backbone were identified, with elution profiles consistent with those of ELISA. The more abundant brevetoxin metabolites in urine were characterized structurally by LC-MS/MS. With the exception of BTX-3, brevetoxin metabolites in urine differed from those found in shellfish and in shellfish meal remnants. Proposed structures of these major urinary metabolites are methylsulfoxy BTX-3, 27-epoxy BTX-3, and reduced BTX-B5. BTX-3 was found in all specimens examined. BTX-3 concentrations in urine, as determined by LC-MS/MS, correlated well with composite toxin measurements by ELISA (r(2) = 0.96). BTX-3 is a useful biomarker for confirmation of clinical diagnosis of NSP. Published by Elsevier Ltd.