Characterisation of a potential biomarker of phospholipidosis from amiodarone-treated rats

被引:53
作者
Mortuza, GB
Neville, WA
Delaney, J
Waterfield, CJ
Camilleri, P
机构
[1] GlaxoSmithKline, Safety Assessment, ToxicoProtem & BioAnal, Harlow CM19 5AW, Essex, England
[2] GlaxoSmithKline, Safety Assessment, Cellular & Biochem Toxicol, Ware SG12 0DP, Herts, England
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS | 2003年 / 1631卷 / 02期
关键词
phospholipidosis (PLD); lyso-bis-phosphatidic acid (LBPA); bis(monoglycero)phosphate (BMP); phosphatidylcholine (PC); amiodarone; high performance liquid chromatography (HPLQ; electrospray ionisation-mass spectrometry (ESI-MS); cationic amphiphilic drug (CAD);
D O I
10.1016/S1388-1981(02)00361-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A novel and relatively simple analytical method for the separation, characterisation and semi-quantitation of phospholipids (PLs) from extracts of complex biological samples has been developed. This methodology allows PL extracts from cells and tissues to be analysed by liquid chromatography (LC) coupled to electrospray ionisation mass spectrometry (ESI-MS). Complex mixtures of PLs were separated on a high-performance liquid chromatography (HPLC) system using 0.5% ammonium hydroxide in methanol/water/hexane/formate mixture with UV detection at 205 nm. Identification and structural characterisation of molecular species were carried out utilising ESI-MS and MS/MS in the negative ion mode. The abnormal accumulation of PLs (phospholipidosis) was induced in male Sprague-Dawley rats by administration of the cationic amphiphilic drug (CAD), amiodarone. Analysis of the PL profile of liver and lung tissues, lymphocytes and serum from treated rats was carried out using this analytical procedure (LC-ESI/MS/MS). Differences in PL profiles between treated and untreated animals were highlighted by principal component analysis (PCA). This led to the selection of a potential metabolic marker of phospholipidosis (PLD) identified as a lyso-bis-phosphatidic acid (LBPA) derivative, also known as bis(monoglycero)phosphate (BMP). This PL was absent in control animals but was present in quantifiable amounts in all samples from amiodarone-treated rats. (C) 2003 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:136 / 146
页数:11
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