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

Drug-induced phospholipidosis is a common side effect of the pharmacological treatment. Although mostly reversible, it can lead to deleterious consequences, including inflammation and fibrosis. While it can be readily detected in tissue biopsies or cell cultures, biomarkers that can be measured noninvasively remain scarce. We used a panel of four compounds known to induce phospholipidosis to investigate three primary target tissues as potential new biomarkers. Using mass spectrometry imaging, followed by analysis with prediction models and feature-wise statistical analysis, we identified over 150 mass/charge features correlated with DIPL in general or in specific tissues, many of which yielded database hits in the LipidMaps DB in molecule classes linked to DIPL before. Our data set provides a foundation for annotating reliable biomarkers in blood and urine.