Arsenite-induced cytotoxicity in dorsal root ganglion explants

Chou, Yueh‐Ching; Chao, Pei-Ling; Tsai, Ming-Tzu; Cheng, Henrich; Chen, K.B.; Yang, D.M.; Yang, Chun-Chuan; Lin, Anya Maan Yuh

doi:10.1016/j.freeradbiomed.2007.12.014

Cited by 16 publications

(14 citation statements)

References 49 publications

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“…Activation of p38 mitogen‐activated protein kinase has been reported in arsenic‐induced apoptosis in cerebellar neuronal culture [11], nigrostriatal dopaminergic system of rat brain [13, 14] and DRG explants [18]. Our data show that melatonin inhibited both arsenite‐induced phosphorylation of p38 and arsenite‐induced DNA fragmentation in DRG explants, suggesting that melatonin is protective against arsenite‐induced apoptosis in the PNS.…”

Section: Discussionsupporting

confidence: 60%

“…In this study, we were the first to employ DRG explants to demonstrate the protective effect of melatonin on arsenite‐induced peripheral neurotoxicity in several aspects. First of all, expression of HO‐1 and HSP 70 proteins was found to be proportional to arsenite exposure [18], and our data demonstrate that melatonin concentration‐dependently reduced arsenite‐induced elevation in stress protein levels, indicating that melatonin is capable of reducing arsenite‐induced oxidative stress in DRG explants.…”

Section: Discussionsupporting

confidence: 53%

“…Three ER membrane proteins, RNA‐dependent protein kinase‐like ER kinase (PERK), ATF‐6 and Ire1α/β, are known to sense ER stress and activate three unfolding protein response pathways [45–47], (i) PERK‐induced upregulation of ATF‐4 targets, including transcriptional activation of genes for CHOP, (ii) ATF‐6‐induced increases in chaperone proteins including CHOP and BiP and (iii) Ire1α/β‐induced activation of procaspase‐12 [43]. The involvement of ER stress had been excluded in arsenite‐induced neurotoxicity in one study [48]; however, our previous studies have shown activation of the ER pathway in arsenite‐induced apoptosis in nigrostriatal dopaminergic system of rat brain [13, 14] and DRG explants [18]. In this study, melatonin inhibited arsenite‐induced elevation of ATF6 and CHOP (i.e.…”

Section: Discussionmentioning

confidence: 99%

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Melatonin inhibits arsenite‐induced peripheral neurotoxicity

Lin

Feng

Chao

et al. 2008

Journal of Pineal Research

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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.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

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Melatonin inhibits arsenite‐induced peripheral neurotoxicity

Lin

Feng

Chao

et al. 2008

Journal of Pineal Research

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“…Previous studies also showed that As-mediated neurotoxicity was involved in apoptosis and demyelination of peripheral neurons including dorsal root ganglion (DRG) neurons 23, 24 . As-mediated neurotoxicity was also shown to be involved in increased levels of oxidative stress markers including heme oxiygenase 1 (HO-1) and decreased levels of procaspases 3 and 12 in DRG explants 25 . Further study is needed to determine whether in vivo exposure to As induces oxidative stress, apoptosis and demyelination in auditory neurons and to elucidate the molecular mechanism by which hair cells were not affected by exposure to As in this study.…”

Section: Discussionmentioning

confidence: 99%

Oral exposure to arsenic causes hearing loss in young people aged 12–29 years and in young mice

Ohgami

Omata

et al. 2017

Sci Rep

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There is no information on the association between oral exposure to arsenic (As) and hearing loss in humans or mice. In this combined epidemiological study and experimental study, the association of oral exposure to As with hearing loss in people aged 12–29 years and young mice was examined. Subjects in the exposure group (n = 48), who were drinking tube well water contaminated with As, showed significantly higher risks of hearing loss at 4 kHz [odds ratio (OR) = 7.60; 95% confidence interval (CI): 1.56, 57.88], 8 kHz (OR = 5.00; 95% CI: 1.48, 18.90) and 12 kHz (OR = 8.72; 95% CI: 2.09, 47.77) than did subjects in the control group (n = 29). We next performed an experiment in which young mice were exposed to As via drinking water at 22.5 mg/L, which is a much greater concentration than that in human studies. The exposure group showed hearing loss and accumulation of As in inner ears. Ex vivo exposure of the organ of Corti from mice exposed to As significantly decreased the number of auditory neurons and fibers. Thus, our combined study showed that oral exposure to As caused hearing loss in young people and young mice.

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“…In the PNS, sodium arsenite (arsenite) has been shown to inhibit axonal growth in the dorsal root ganglion (DRG) explants 10 . Furthermore, apoptosis is reportedly involved in the arsenite‐treated DRG explants 11,12 or DRG of rats receiving oral arsenite (unpublished data). In the CNS, arsenic‐induced deficits include a reduction in locomotor activity, sleep disturbances, auditory–evoked potential, and learning and memory deficits 1,3 .…”

Section: Introductionmentioning

confidence: 94%

Arsenite induces oxidative injury in rat brain

Fan

Chao

Lin

2010

Annals of the New York Academy of Sciences

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Sodium arsenite (arsenite)-induced neurotoxicity and its interaction with ferrous citrate (iron) was investigated in rat brain. In vitro data showed that arsenite (1-10 micromol/L) concentration dependently increased lipid peroxidation and the potency of arsenite was less than that of iron. The oxidative activity of arsenite, sodium arsenate (arsenate), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were evaluated by inducing lipid peroxidation in cortical homogenates, and the potency for this effect was as follows: arsenite > arsenate > MMA and DMA. Several well-known antioxidants, including glutathione, melatonin, and beta-estradiol inhibited arsenite-induced lipid peroxidation in a concentration-dependent manner. Our in vivo study employed intranigral infusion of arsenite (5 nmol) in the substantia nigra (SN) of anesthetized rats. Four hours to 7 days after infusion, lipid peroxidation was elevated while glutathione was depleted in the infused SN. The dopamine content in the striatum ipsilateral to arsenite-infused SN was first elevated 24 h and then decreased 7 days after intranigral infusion of arsenite. Using pretreatment of l-buthionine-[S,R]-sulfoximine (l-BSO, i.c.v.) to reduce glutathione content in rat brain, arsenite-induced oxidative injury was augmented. Low doses of arsenite (1.5 nmol) and iron (3 nmol) alone induced minimal oxidative injury; however, co-infusion of arsenite and iron augmented neurotoxicity, including elevated lipid peroxidation and reduced striatal dopamine content. Moreover, expression of heme oxygenase-1, alpha-synuclein aggregation, and DNA fragmentation were significantly enhanced in SN co-infused with low doses of arsenite and iron. Taken together, our study demonstrates that arsenite was less potent than iron in inducing oxidative stress. Furthermore, concomitant arsenite and iron potentiated oxidative injury in the nigrostriatal dopaminergic system, indicating that interaction of metals plays a more clinically-relevant role in pathophysiology of central nervous system neurodegeneration.

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Arsenite-induced cytotoxicity in dorsal root ganglion explants

Cited by 16 publications

References 49 publications

Melatonin inhibits arsenite‐induced peripheral neurotoxicity

Melatonin inhibits arsenite‐induced peripheral neurotoxicity

Oral exposure to arsenic causes hearing loss in young people aged 12–29 years and in young mice

Arsenite induces oxidative injury in rat brain

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