19286452

Source:http://linkedlifedata.com/resource/pubmed/id/19286452

Download in:

Switch to

Custom View

Named Graph Language Inference

Statements in which the resource exists as a subject.
Predicate	Object
rdf:type	pubmed:Citation
lifeskim:mentions	umls-concept:C0007634, umls-concept:C0058903, umls-concept:C0079411, umls-concept:C0439825, umls-concept:C0599946, umls-concept:C0812281, umls-concept:C1417701, umls-concept:C1879547
pubmed:issue	1-2
pubmed:dateCreated	2009-4-20
pubmed:abstractText	Ebselen, an organoselenium compound that acts as a glutathione peroxidase mimetic, has been demonstrated to possess antioxidant and anti-inflammatory activities. However, the molecular mechanism underlying this effect is not fully understood in auditory cells. The purpose of the present study is to investigate the protective effect of ebselen against cisplatin-induced toxicity in HEI-OC1 auditory cells, organotypic cultures of cochlear explants from two-day postnatal rats (P(2)) and adult Balb/C mice. Pretreatment with ebselen ameliorated apoptotic death induced by cisplatin in HEI-OC1 cells and organotypic cultures of Corti's organ. Ebselen pretreatment also significantly suppressed cisplatin-induced increases in intracellular reactive oxygen species (ROS), intracellular reactive nitrogen species (RNS) and lipid peroxidation levels. Ebselen dose-dependently increased the expression level of an antioxidant response element (ARE)-luciferase reporter in HEI-OC1 cells through the translocation of Nrf2 into the nucleus. Furthermore, we found that pretreatment with ebselen significantly restored Nrf2 function, whereas it ameliorated the cytotoxicity of cisplatin in cells transfectants with either a pcDNA3.1 (control) or a DN-Nrf2 (dominant-negative) plasmid. We also observed that Nrf2 activation by ebselen increased the expression of phase II antioxidant genes, including heme oxygenase (HO-1), NAD(P)H:quinine oxidoreductase, and gamma-glutamylcysteine synthetase (gamma-GCS). Treatment with ebselen resulted in an increased expression of HO-1 and intranuclear Nrf2 in hair cells of organotypic cultured cochlea. After intraperitoneal injection with cisplatin, auditory brainstem responses (ABRs) threshold was measured on 8th day in Balb/C mice. ABR threshold shift was marked occurred in mice injected with cisplatin (16 mg/kg, n=5; Click and 8-kHz stimuli, p<0.05; 4, 16 and 32 kHz, p<0.01), whereas that of animal group which was treated with cisplatin and ebselen was not significantly changed. These results suggest that ebselen activates the Nrf2-ARE signaling pathway, which ultimately prevents free radical stresses from cisplatin and further contributes to protect auditory sensory hair cells from free radicals produced by cisplatin.
pubmed:language	eng
pubmed:journal	http://linkedlifedata.com/resource/pubmed/journal/7900445
pubmed:citationSubset	IM
pubmed:chemical	http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Azoles, http://linkedlifedata.com/resource/pubmed/chemical/Cisplatin, http://linkedlifedata.com/resource/pubmed/chemical/Luciferases, http://linkedlifedata.com/resource/pubmed/chemical/NF-E2-Related Factor 2, http://linkedlifedata.com/resource/pubmed/chemical/Neuroprotective Agents, http://linkedlifedata.com/resource/pubmed/chemical/Nfe2l2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Organoselenium Compounds, http://linkedlifedata.com/resource/pubmed/chemical/Phenols, http://linkedlifedata.com/resource/pubmed/chemical/Plant Extracts, http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species, http://linkedlifedata.com/resource/pubmed/chemical/antioxidant biofactor AOB, http://linkedlifedata.com/resource/pubmed/chemical/ebselen
pubmed:status	MEDLINE
pubmed:month	May
pubmed:issn	1878-5891
pubmed:author	pubmed-author:ChungSang-YoungSY, pubmed-author:HanA LumAL, pubmed-author:KimEun-SookES, pubmed-author:KimHyung-JinHJ, pubmed-author:KimJin-KyungJK, pubmed-author:KimSe-JinSJ, pubmed-author:KimYunhaY, pubmed-author:LeeHo-KyunHK, pubmed-author:LeeJeong-HanJH, pubmed-author:ParkChannyC, pubmed-author:ParkRaekilR, pubmed-author:SoHongseobH, pubmed-author:YounMyung-JaMJ
pubmed:issnType	Electronic
pubmed:volume	251
pubmed:owner	NLM
pubmed:authorsComplete	Y
pubmed:pagination	70-82
pubmed:meshHeading	pubmed-meshheading:19286452-Animals, pubmed-meshheading:19286452-Antineoplastic Agents, pubmed-meshheading:19286452-Apoptosis, pubmed-meshheading:19286452-Azoles, pubmed-meshheading:19286452-Cell Line, Transformed, pubmed-meshheading:19286452-Cisplatin, pubmed-meshheading:19286452-Evoked Potentials, Auditory, Brain Stem, pubmed-meshheading:19286452-Gene Expression, pubmed-meshheading:19286452-Genes, Reporter, pubmed-meshheading:19286452-Lipid Peroxidation, pubmed-meshheading:19286452-Luciferases, pubmed-meshheading:19286452-Mice, pubmed-meshheading:19286452-Mice, Inbred BALB C, pubmed-meshheading:19286452-NF-E2-Related Factor 2, pubmed-meshheading:19286452-Neuroprotective Agents, pubmed-meshheading:19286452-Organ Culture Techniques, pubmed-meshheading:19286452-Organ of Corti, pubmed-meshheading:19286452-Organoselenium Compounds, pubmed-meshheading:19286452-Phenols, pubmed-meshheading:19286452-Plant Extracts, pubmed-meshheading:19286452-Reactive Oxygen Species, pubmed-meshheading:19286452-Transfection
pubmed:year	2009
pubmed:articleTitle	Ebselen attenuates cisplatin-induced ROS generation through Nrf2 activation in auditory cells.
pubmed:affiliation	Vestibulocochlear Research Center (VCRC), Department of Microbiology, Wonkwang University College of Medicine, 344-2 Shinyong-dong, Iksan, Jeonbuk 570-749, South Korea.
pubmed:publicationType	Journal Article, Research Support, Non-U.S. Gov't