Screen for Tissue-Specific Markers of Drug-Induced Phospholipidosis Using Mass Spectrometry Imaging

Area of Science:

• Biochemistry
• Pharmacology
• Biomarker Discovery

Background:

• Drug-induced phospholipidosis (DIPL) is a frequent adverse effect of pharmacotherapy.
• While often reversible, DIPL can cause significant tissue damage, including inflammation and fibrosis.
• Current detection methods rely on invasive tissue biopsies or cell cultures, necessitating noninvasive alternatives.

Purpose of the Study:

• To identify novel, noninvasive biomarkers for drug-induced phospholipidosis.
• To investigate specific tissues as potential sources for DIPL biomarkers.
• To establish a foundation for detecting DIPL through blood and urine analysis.

Main Methods:

• Utilized a panel of four known phospholipidosis-inducing compounds.
• Employed mass spectrometry imaging on three primary target tissues.
• Applied prediction models and feature-wise statistical analysis to identify mass/charge features.

Main Results:

• Identified over 150 mass/charge features associated with DIPL.
• Correlated features with DIPL generally and in specific tissues.
• Many identified features matched known lipid classes linked to DIPL in the LipidMaps database.

Conclusions:

• The study provides a dataset foundational for annotating reliable biomarkers for DIPL.
• Identified features represent potential noninvasive biomarkers detectable in blood and urine.
• This research paves the way for improved diagnostics and monitoring of drug-induced phospholipidosis.