Abstract
Cationic amphiphilic drugs and aminoglycoside antibiotics can induce phospholipidosis (PLD), an abnormal accumulation of phospholipids in lysosome-derived vesicles, in preclinical studies. The incidence of PLD in patients and its clinical relevance are difficult to assess without noninvasive biomarkers. Di-docosahexaenoyl bis(monoacylglycerol)phosphate (di-22:6-BMP) is a phospholipid that is enriched in lysosomal membranes and a proposed urinary biomarker of drug-induced PLD. The specificity of di-22:6-BMP for PLD was compared to other phospholipid species that can increase in urine with nephrotoxicity. Using liquid chromatography coupled to mass spectrometry, 12 phospholipids were assayed in the urine of rats treated with drugs that induced PLD or caused renal or skeletal muscle injury. In receiver operating curve analyses, urinary di-22:6-BMP was a significantly better predictor of PLD and the least predictive of tissue injury of the phospholipids assayed. The data provide evidence supporting the use of di-22:6-BMP as a urinary biomarker of PLD in rats.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Biomarkers / urine
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Cell Adhesion Molecules / urine
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Cisplatin / adverse effects
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Drug-Related Side Effects and Adverse Reactions*
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Female
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Gentamicins / adverse effects
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Hexestrol / adverse effects
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Hexestrol / analogs & derivatives
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Kidney Diseases / chemically induced*
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Kidney Diseases / pathology
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Kidney Diseases / urine
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Lipocalin-2
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Lipocalins / urine
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Liver / drug effects
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Liver / pathology
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Lung / drug effects
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Lung / pathology
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Lymph Nodes / drug effects
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Lymph Nodes / pathology
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Lysophospholipids / urine*
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Male
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Muscle, Skeletal / drug effects
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Muscle, Skeletal / metabolism
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Muscle, Skeletal / pathology
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Osteopontin / urine
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Phospholipids / urine*
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Rats
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Rats, Inbred F344
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Rats, Sprague-Dawley
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Simvastatin / adverse effects
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Spleen / drug effects
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Spleen / pathology
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Troponin I / blood
Substances
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Biomarkers
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Cell Adhesion Molecules
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Gentamicins
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Havcr1protein, rat
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Lcn2 protein, rat
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Lipocalin-2
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Lipocalins
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Lysophospholipids
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Phospholipids
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Troponin I
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didocosahexaenoyl bis(monoacylglycerol) phosphate
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Osteopontin
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Hexestrol
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Simvastatin
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Cisplatin
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hexestrol bis(diethylaminoethyl ether)