Phospholipidosis

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Phospholipidosis is a lysosomal storage disorder characterized by the excess accumulation of phospholipids in tissues. [1] [2] [3] Certain cases may be triggered by medications. [4]

The traditional method to evaluate drug-induced phospholipidosis (DIPL) is visual confirmation of myeloid bodies in tissues by electron microscopy. Electron microscopy has limited utility to monitor DIPL in humans because of the invasive nature of acquiring patient tissue biopsy samples. A qualified biomarker of DIPL in the blood or urine is needed to provide a more routine, non-invasive, and cost effective means to monitor DIPL in the clinic. [5]

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References

  1. Anderson N, Borlak J (October 2006). "Drug-induced phospholipidosis". FEBS Letters. 580 (23): 5533–40. doi:10.1016/j.febslet.2006.08.061. PMID   16979167. S2CID   39498487.
  2. Reasor MJ, Hastings KL, Ulrich RG (July 2006). "Drug-induced phospholipidosis: issues and future directions". Expert Opinion on Drug Safety. 5 (4): 567–83. doi:10.1517/14740338.5.4.567. PMID   16774494. S2CID   28228669.
  3. Nonoyama T, Fukuda R (2008). "Drug induced phospholipidosis pathological aspects and its prediction". J Toxicol Pathol. 21: 9–24. doi: 10.1293/tox.21.9 .
  4. Shayman JA, Abe A (March 2013). "Drug induced phospholipidosis: an acquired lysosomal storage disorder". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1831 (3): 602–11. doi:10.1016/j.bbalip.2012.08.013. PMC   3528828 . PMID   22960355.
  5. Tengstrand EA, Miwa GT, Hsieh FY (May 2010). "Bis(monoacylglycerol)phosphate as a non-invasive biomarker to monitor the onset and time-course of phospholipidosis with drug-induced toxicities". Expert Opinion on Drug Metabolism & Toxicology. 6 (5): 555–70. doi:10.1517/17425251003601961. PMID   20370598. S2CID   207490774.