Bis(monoacylglycerol)phosphate as a non-invasive biomarker to monitor the onset and time-course of phospholipidosis with drug-induced toxicities

Expert Opin Drug Metab Toxicol. 2010 May;6(5):555-70. doi: 10.1517/17425251003601961.

Abstract

Importance to the field: Drug-induced phospholipidosis (PL) is a phospholipid storage disorder characterized by the accumulation of multi-lamellar bodies (myeloid bodies) in tissues. A major unanswered question is whether PL represents a benign adaptive response, symptom or early event in drug toxicity. The absence of a non-invasive biomarker to monitor tissue PL has made it difficult to determine the prevalence and implications of PL in the clinic. As a result, the interpretation of PL in risk assessment remains uncertain in preclinical and clinical drug development.

Areas covered in this review: This review describes the rationale for bis(monoacylglycerol)phosphate (BMP) as a biomarker of PL and explores the potential links between PL and the toxicities of drugs.

What the reader will gain: The similarities between the hypothesized roles of BMP in PL and Niemann-Pick type C disease are discussed. The potential implications of PL for cellular function are described in the context of drug-induced QT prolongation, myopathy and renal toxicity.

Take home message: A specific species of BMP, di-docosahexaenoyl-BMP, should be investigated further as a non-invasive biomarker to monitor the onset and time course of PL and to better understand the functional consequences which could contribute to the toxicities of drugs.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Drug Design
  • Drug-Related Side Effects and Adverse Reactions*
  • Humans
  • Lipidoses / chemically induced*
  • Lipidoses / diagnosis
  • Lipidoses / physiopathology
  • Long QT Syndrome / chemically induced
  • Lysophospholipids / metabolism*
  • Monoglycerides / metabolism*
  • Niemann-Pick Disease, Type C / diagnosis
  • Phospholipids / metabolism
  • Risk Assessment / methods
  • Time Factors

Substances

  • Biomarkers
  • Lysophospholipids
  • Monoglycerides
  • Phospholipids
  • bis(monoacylglyceryl)phosphate