Reactive oxygen species play an important role in iodoacetate-induced neurotoxicity in primary rat neuronal cultures and in differentiated PC12 cells

Oded Sperling, Yael Bromberg, Harrietta Oelsner, Esther Zoref-Shani*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

The role of reactive oxygen species in the pathogenesis of the neurotoxicity associated with ischemia-reperfusion, was investigated in a model of primary rat neuronal cultures and of differentiated PC12 cells, subjected to chemical ischemia by iodoacetic acid (IAA, 2.5 h) followed by a short period of reperfusion (1 h). The injury to the cells was assessed by lactate dehydrogenase (LDH) release into the culture media. The PC12 cells exhibited relative resistance to IAA cytotoxicity. Therefore these cells were studied at a 4-fold higher IAA concentration (400 μM instead of 100 μM for the neurons). The injury to both cell types was significantly greater in the short post-insult reperfusion (PIR) period than during the insult period. The presence, during the combined insult and PIR periods, of α-tocopherol (100 μM), melatonin (1 mM) and LY231617 (5 μM), conferred to both cell types considerable protection against the injury occurring during the insult and during the PIR periods (assessed separately). Superoxide dismutase (SOD; 500 IU/ml) conferred protection to the neurons, but not to the PC12 cells. When exposure to the antioxidants was limited to the short (15 min) pre insult period, only LY231617 conferred protection. In the neurons the protection occurred only during the insult period, whereas in the PC12 cells during both the insult and PIR periods. When the exposure to the antioxidants was limited to the PIR period, only SOD conferred protection and only in the neuronal cultures. These findings suggest that neuronal damage caused during ischemia-reperfusion can be diminished markedly by co-presence of antioxidants during the insult period. Certain antioxidants may protect the neurons even when present only before or after the insult.

Original languageEnglish
Pages (from-to)137-140
Number of pages4
JournalNeuroscience Letters
Volume351
Issue number3
DOIs
StatePublished - 20 Nov 2003

Keywords

  • Cultured neurons
  • Iodoacetic acid
  • LY231617
  • Melatonin
  • PC12 cells
  • Reactive oxygen species (ROS)
  • Superoxide dismutase
  • α-Tocopherol

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