Prostaglandin release by spinal cord injury mediates production of hydroxyl radical, malondialdehyde and cell death: A site of the neuroprotective action of methylprednisolone

Danxia Liu, Liping Li, Lezel Augustus

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

The present study explores in viva whether and how prostaglandin F (PGF), a membrane phospholipid hydrolysis product, causes neuronal death. The concentration of PGF measured by microdialysis sampling increased three-fold immediately following impact injury to the rat spinal cord. Administration of PGF into the cord through a dialysis fiber caused significant cell loss, increased extracellular levels of hydroxyl radicals and malondialdehyde - an end product of membrane lipid peroxidation - to 3.3 and 2.3 times basal levels, respectively. This suggests that PGF-induced cell death is partly due to hydroxyl radical-triggered peroxidation. Generating hydroxyl radical by administering Fenton's reagents into the cord through the fibers significantly increased malondialdehyde production - the first direct in viva evidence that hydroxyl radical triggers membrane lipid peroxidation. Methylprednisolone significantly reduced the release of PGF upon spinal cord injury and blocked PGF-induced hydroxyl radical and malondialdehyde production, but did not significantly reduce Fenton's reagent-induced malondialdehyde production, despite the production of more malondialdehyde by PGF. This suggests that methylprednisolone may not directly scavenge hydroxyl radical, and that its 'antioxidant' effect is a consequence of blocking the pathways for producing toxic PGF and for PGF-induced hydroxyl radical formation, thereby reducing membrane lipid peroxidation.

Original languageEnglish (US)
Pages (from-to)1036-1047
Number of pages12
JournalJournal of neurochemistry
Volume77
Issue number4
DOIs
StatePublished - 2001

Keywords

  • Hydroxyl radical
  • Malondialdehyde
  • Membrane phospholipid hydrolysis and peroxidation
  • Methylprednisolone
  • PGF
  • Secondary spinal cord injury

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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