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N ‐Acetylcysteine Attenuates Arsenite‐Induced Oxidative Injury in Dorsal Root Ganglion Explants
Author(s) -
CHAO P.L.,
FAN S.F.,
CHOU Y.H.,
LIN ANYA M.Y.
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1403.020
Subject(s) - arsenite , glutathione , oxidative stress , arsenic toxicity , chemistry , acetylcysteine , mitochondrion , biochemistry , pharmacology , microbiology and biotechnology , biology , toxicity , arsenic , antioxidant , enzyme , organic chemistry
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.