Biomarkers to monitor drug-induced phospholipidosis.
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.
Baronas
Elizabeth Tengstrand
ET
Nextcea, Inc., 3 Goffe Road, Lexington, MA 02421, USA.
Lee
Ju-Whei
JW
Alden
Carl
C
Hsieh
Frank Y
FY
D000638:Amiodarone / Q000009:adverse effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D017963:Azithromycin / Q000009:adverse effects; D015415:Biomarkers / Q000652:urine; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D005839:Gentamicins / Q000009:adverse effects; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008064:Lipidoses / Q000139:chemically induced / Q000473:pathology / Q000652:urine*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008246:Lysophospholipids / Q000652:urine*; D008279:Magnetic Resonance Imaging; D008297:Male; D008854:Microscopy, Electron; D010713:Phosphatidylcholines / Q000652:urine; D010714:Phosphatidylethanolamines / Q000652:urine; D010716:Phosphatidylinositols / Q000652:urine; D010743:Phospholipids / Q000652:urine*; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D000900:Anti-Bacterial Agents; D015415:Biomarkers; D005839:Gentamicins; D008246:Lysophospholipids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010716:Phosphatidylinositols; D010743:Phospholipids; C517624:didocosahexaenoyl bis(monoacylglycerol) phosphate; C483858:phosphatidylethanolamine; D017963:Azithromycin; D000638:Amiodarone