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Title: Biomarkers to monitor drug-induced phospholipidosis

Abstract

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.

Authors:
 [1];  [2];  [3];  [4]
  1. Nextcea, Inc., 3 Goffe Road, Lexington, MA 02421 (United States)
  2. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115 (United States)
  3. Drug Safety and Disposition, Millennium Pharmaceuticals, Inc. 75 Sidney Street, Cambridge, MA 02139 (United States)
  4. Nextcea, Inc., 3 Goffe Road, Lexington, MA 02421 (United States). E-mail: frank.hsieh@nextcea.com
Publication Date:
OSTI Identifier:
20976840
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 218; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2006.10.015; PII: S0041-008X(06)00377-2; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BIOLOGICAL MARKERS; DRUGS; KIDNEYS; LECITHINS; LIQUID COLUMN CHROMATOGRAPHY; LIVER; LUNGS; LYMPH NODES; MASS SPECTROSCOPY; PHOSPHATES; RATS; TRANSMISSION ELECTRON MICROSCOPY; URINE

Citation Formats

Baronas, Elizabeth Tengstrand, Lee, Ju-Whei, Alden, Carl, and Hsieh, Frank Y. Biomarkers to monitor drug-induced phospholipidosis. United States: N. p., 2007. Web. doi:10.1016/j.taap.2006.10.015.
Baronas, Elizabeth Tengstrand, Lee, Ju-Whei, Alden, Carl, & Hsieh, Frank Y. Biomarkers to monitor drug-induced phospholipidosis. United States. doi:10.1016/j.taap.2006.10.015.
Baronas, Elizabeth Tengstrand, Lee, Ju-Whei, Alden, Carl, and Hsieh, Frank Y. Mon . "Biomarkers to monitor drug-induced phospholipidosis". United States. doi:10.1016/j.taap.2006.10.015.
@article{osti_20976840,
title = {Biomarkers to monitor drug-induced phospholipidosis},
author = {Baronas, Elizabeth Tengstrand and Lee, Ju-Whei and Alden, Carl and Hsieh, Frank Y.},
abstractNote = {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.},
doi = {10.1016/j.taap.2006.10.015},
journal = {Toxicology and Applied Pharmacology},
number = 1,
volume = 218,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}