Biomarkers to monitor drug-induced phospholipidosis
- 关键词：Drug-induced phospholipidosis ; Amiodarone ; Azithromycin ; Gentamicin ; Mass spectrometry ; Biomarker ; Phospholipids ; Cationic amphiphilic drugs
- 刊名：Toxicology and Applied Pharmacology
- 出版年：2007
- 期刊代码：58_0041008x
- 类别：pha
- 出版时间：1 January 2007
- 卷：218
- 期：1
- 页码：72-78
- 文件大小：219 K
摘要
Di-docosahexaenoyl (C22:6)-bis(monoacylglycerol) phosphate (BMP) was identified as a promising phospholipidosis (PL) biomarker in rats treated with either amiodarone, gentamicin, or azithromycin. Sprague–Dawley rats received either amiodarone (150 mg/kg), gentamicin (100 mg/kg) or azithromycin (30 mg/kg) once daily for ten consecutive days. Histopathological examination of tissues by transmission electron microscopy (TEM) indicated different degrees of accumulation of phospholipidosis in liver, lung, mesenteric lymph node, and kidney of drug-treated rats but not controls. Liquid chromatography coupled to mass spectrometry (LC/MS) was used to identify levels of endogenous biochemical profiles in rat urine. Urinary levels of di-docosahexaenoyl (C22:6)-bis(monoacylglycerol) phosphate (BMP) correlated with induction of phospholipidosis for amiodarone, gentamicin and azithromycin. Rats treated with gentamicin also had increased urinary levels of several phosphatidylinositol (PI), phosphatidylcholine (PC), and phosphatidylethanolamine (PE) species.