Disulfiram Neurotoxicity: Decrements in Ethanolamine, Serine, and Inositol Glycerophospholipids

Abstract

Paul L Wood, Ryan S Alexander, Cameron C Felty

Aim: Disulfiram has rare serious neurotoxicities including optic neuropathy, peripheral neuropathy and basal ganglia lesions. Since the mechanism of these toxicities is not understood, we undertook a lipidomics analysis of the effects of disulfiram on human lymphoblasts. Materials and Methods: Human lymphoblasts were incubated with disulfiram, and the cellular lipidome was analyzed by ESI-high resolution mass spectrometry. Results: Disulfiram decreased the levels of a large number of glycerophospholipids, sphingolipids, and diacylglycerols. Conclusion: Disulfiram has dramatic effects on the levels of structural lipids in human lymphoblasts. These actions may explain the neurotoxicities of this drug in humans.