Phospholipidosis in neurons caused by posaconazole, without evidence for functional neurologic effects

Mark E. Cartwright, Janet Petruska, Joseph C. Arezzo, Doyle Frank, Mona Litwak, Richard E. Morrissey, James MacDonald, Thomas E. Davis

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The azole antifungal drug posaconazole caused phospholipidosis in neurons of the central nervous system, dorsal root ganglia of the spinal cord, and myenteric plexus in chronic toxicity studies in dogs. The time of onset, light and electron microscopic features, neurologic and electrophysiologic effects on the central and peripheral nervous systems, and potential for regression were investigated in a series of studies with a duration of up to one year. Nuclei of the medulla oblongata were the prominently affected areas of the brain. Neurons contained cytoplasmic vacuoles with concentrically whorled plasma membrane-like material (i.e., multilamellar bodies) morphologically identical to that commonly caused in other tissues by cationic amphiphilic drugs. Some axons in the brain and spinal cord were swollen and contained granular eosinophilic, electron-dense lysosomes. There were no features suggesting degeneration or necrosis of neurons or any associated elements of nervous tissue. The earliest and most consistent onset was in neurons of dorsal root ganglia. The observed neural phospholipidosis did not result in any alteration in the amplitude or latency of the auditory, visual, or somatosensory evoked potentials. The histopathologic changes did not progress or regress within the three-month postdose period. The results indicate that phospholipidosis can be induced in central and peripheral neurons of dogs by administration of posaconazole, but this change is not associated with functional effects in the systems evaluated.

Original languageEnglish (US)
Pages (from-to)902-910
Number of pages9
JournalToxicologic Pathology
Volume37
Issue number7
DOIs
StatePublished - Dec 2009

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Nervous System
Neurons
Spinal Ganglia
Neurology
Brain
Spinal Cord
Central Nervous System
Dogs
Electrons
Tissue
Nerve Tissue
Myenteric Plexus
Azoles
Auditory Evoked Potentials
Medulla Oblongata
Somatosensory Evoked Potentials
Visual Evoked Potentials
Bioelectric potentials
Peripheral Nervous System
Cell membranes

Keywords

  • Dog
  • Function.
  • Neurons
  • Phospholipidosis
  • Posaconazole

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Toxicology
  • Cell Biology
  • Molecular Biology

Cite this

Cartwright, M. E., Petruska, J., Arezzo, J. C., Frank, D., Litwak, M., Morrissey, R. E., ... Davis, T. E. (2009). Phospholipidosis in neurons caused by posaconazole, without evidence for functional neurologic effects. Toxicologic Pathology, 37(7), 902-910. https://doi.org/10.1177/0192623309348521

Phospholipidosis in neurons caused by posaconazole, without evidence for functional neurologic effects. / Cartwright, Mark E.; Petruska, Janet; Arezzo, Joseph C.; Frank, Doyle; Litwak, Mona; Morrissey, Richard E.; MacDonald, James; Davis, Thomas E.

In: Toxicologic Pathology, Vol. 37, No. 7, 12.2009, p. 902-910.

Research output: Contribution to journalArticle

Cartwright, ME, Petruska, J, Arezzo, JC, Frank, D, Litwak, M, Morrissey, RE, MacDonald, J & Davis, TE 2009, 'Phospholipidosis in neurons caused by posaconazole, without evidence for functional neurologic effects', Toxicologic Pathology, vol. 37, no. 7, pp. 902-910. https://doi.org/10.1177/0192623309348521
Cartwright, Mark E. ; Petruska, Janet ; Arezzo, Joseph C. ; Frank, Doyle ; Litwak, Mona ; Morrissey, Richard E. ; MacDonald, James ; Davis, Thomas E. / Phospholipidosis in neurons caused by posaconazole, without evidence for functional neurologic effects. In: Toxicologic Pathology. 2009 ; Vol. 37, No. 7. pp. 902-910.
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