Melatonin inhibits arsenite-induced peripheral neurotoxicity

Anya M.Y. Lin, S. F. Feng, P. L. Chao, C. H. Yang

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

In this study, the effect of melatonin on sodium arsenite (arsenite)-induced peripheral neurotoxicity was investigated using dorsal root ganglion (DRG) explants. After 24-hr incubation, arsenite (30 μm) consistently elevated the expression of heat shock protein 70 and haeme oxygenase-1, two well-known stress proteins, in the treated DRG explants. Co-incubation with melatonin (4 and 20 mm) concentration-dependently attenuated arsenite-induced elevation in stress proteins. Furthermore, melatonin inhibited arsenite-induced phosphorylation of p38 and DNA fragmentation. Inhibition by melatonin of arsenite-induced apoptosis was mediated via inactivating both endoplasmic reticulum (ER) and mitochondrial pathways. In the ER pathway, melatonin suppressed arsenite-induced elevation in activating transcription factor-6 and CCAAT/enhancer-binding protein homologous protein in the nuclear fraction of the treated DRG explants. Moreover, melatonin attenuated arsenite-induced activation of caspase 12, an ER-specific enzyme. In the mitochondrial pathway, arsenite-induced increases in Bcl-2 levels and cytosolic cytochrome c were reduced by melatonin. At the same time, melatonin inhibited arsenite-induced activation of caspase 3 in the treated DRG explants. Compared with glutathione and N-acetyl cysteine, melatonin was more potent than either in inhibiting arsenite-induced elevation in stress proteins. Taken together, our study demonstrates that melatonin is protective against arsenite-induced neurotoxicity in DRG explants. In addition, melatonin prevented arsenite-induced apoptosis via suppression of ER and mitochondrial activation. Our data suggest that melatonin is potentially a therapy for arsenite-induced peripheral neuropathy.

Original languageEnglish
Pages (from-to)64-70
Number of pages7
JournalJournal of Pineal Research
Volume46
Issue number1
DOIs
StatePublished - Jan 2009

Keywords

  • Arsenite
  • Dorsal root ganglion explants
  • Endoplasmic reticulum stress
  • Melatonin
  • Mitochondria
  • Neurotoxicity

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