N-acetylcysteine attenuates arsenite-induced oxidative injury in dorsal root ganglion explants

P. L. Chao, S. F. Fan, Y. H. Chou, Anya M.Y. Lin*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

21 Scopus citations

Abstract

Chronic exposure to arsenic causes health problems, including peripheral neuropathy. Oxidative stress is one of the mechanisms underlying arsenic-induced neurotoxicity. For this report, we studied the protective effect of N-acetylcysteine (NAC) on arsenic-induced oxidative injury in dorsal root ganglion (DRG) explants. After 24-h incubation, NAC concentration-dependently attenuated arsenite-induced depletion in glutathione (GSH) content and increases in the ratio of oxidized GSH/reduced GSH (GSSG/GSH ratio) in DRG explants. Furthermore, NAC inhibited arsenite-induced elevation in the expression of stress proteins, such as heat shock protein 70 and heme oxygenase 1, as well as arsenite-induced phosphorylation of p38 mitogen-activated protein kinase. Incubation with NAC ameliorated arsenite-induced apoptosis by abolishing both mitochondrial and endoplasmic reticulum (ER) pathways. In the mitochondrial pathway, NAC attenuated arsenite-induced elevation in Bcl-2 level and cytosolic cytochrome c, as well as arsenite-induced reduction in procaspase-3 levels. In the ER pathway, NAC suppressed arsenite-induced increases in activating transcription factor 6 and C/EBP homologous protein in the nuclear fraction. Furthermore, arsenite-induced reductions in procaspase-12 and elevation in BIP and caspase-12, an ER-specific enzyme, were prevented after NAC incubation. Taken together, our results demonstrate that NAC is neuroprotective against arsenite-induced oxidative injury in DRG explants. Furthermore, NAC inhibits arsenite-induced toxicity by inhibiting ER and mitochondrion activation. Our data indicate that NAC is potentially therapeutic for arsenite-induced peripheral neuropathy.

Original languageEnglish
Title of host publicationNeuroprotective Agents
Subtitle of host publicationEighth International Neuroprotection Society Meeting
PublisherBlackwell Publishing Inc.
Pages276-288
Number of pages13
ISBN (Print)9781573316859
DOIs
StatePublished - Dec 2007

Publication series

NameAnnals of the New York Academy of Sciences
Volume1122
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Arsenic
  • DRG explants
  • ER stress
  • Mitochondria
  • NAC
  • Toxicity

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