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Melatonin inhibits arsenite‐induced peripheral neurotoxicity
Author(s) -
Lin Anya M. Y.,
Feng S. F.,
Chao P. L.,
Yang C. H.
Publication year - 2009
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2008.00629.x
Subject(s) - melatonin , arsenite , neurotoxicity , apoptosis , biology , chemistry , endocrinology , microbiology and biotechnology , medicine , biochemistry , toxicity , arsenic , organic chemistry
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 μ m ) 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 m m ) 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.