Comparison of the Diagnostic Accuracy of Di-22:6-Bis(monoacylglycerol)Phosphate and Other Urinary Phospholipids for Drug-Induced Phospholipidosis or Tissue Injury in the Rat.

Thompson KL, Haskins K, Rosenzweig BA, Stewart S, Zhang J, Peters D, Knapton A, Rouse R, Mans D, Colatsky T.
Journal   Int J Toxicol.
Species  
Analytes Measured   Albumin , HAVCR1 KIM-1 , Osteopontin , Troponin I fast-twitch
Matrix Tested   Serum, Urine
Year   2012
Volume   31
Page Numbers   14-24
Application   Toxicology
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.

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