Melatonin inhibits arsenite-induced peripheral neurotoxicity.

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 microm) 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.

• Authors: Anya M Y Lin, S F Feng, P L Chao, C H Yang
• Journal: Journal of pineal research (J Pineal Res) Vol. 46 Issue 1 Pg. 64-70 (Jan 2009) ISSN: 1600-079X [Electronic] England
• PMID: 18715270 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Arsenites
• HSP70 Heat-Shock Proteins
• Heat-Shock Proteins
• Neuroprotective Agents
• Heme Oxygenase-1
• Melatonin
• arsenite

Topics

• Analysis of Variance
• Animals
• Arsenites (antagonists & inhibitors, toxicity)
• Ganglia, Spinal (drug effects, metabolism)
• HSP70 Heat-Shock Proteins (metabolism)
• Heat-Shock Proteins (metabolism)
• Heme Oxygenase-1 (metabolism)
• Male
• Melatonin (metabolism, pharmacology)
• Neuroprotective Agents (metabolism, pharmacology)
• Neurotoxicity Syndromes (metabolism)
• Peripheral Nervous System Diseases (chemically induced, metabolism, prevention & control)
• Rats
• Rats, Sprague-Dawley