| Xanthine oxidase-derived reactive oxygen species mediate 4-oxo-2-nonenal-induced hepatocyte cell death. | |
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MedLine Citation:
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PMID: 20816884 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Among the aldehydes derived from lipid peroxidation, there have been several reports concerning the toxicity of 4-hydroxy-2-nonenal (4-HNE), whereas little information is available about 4-oxo-2-nonenal (4-ONE). In the present study, we examined the effects of 4-HNE and 4-ONE on the cell viability of primary rat hepatocyte cultures. At concentrations of 5, 10, and 20 μM, 4-HNE had no significant effect on the cell viability of primary rat hepatocytes cultures, whereas 4-ONE potently decreased the cell viability in a dose-dependent manner (5-20 μM, 23-69% inhibition). The TUNEL assay showed that 4-ONE causes apoptosis in the cells. 4-ONE also increased 2',7'-dichlorofluorescein-fluorescence intensity from 2',7'-dichlorodihydrofluorescein, an indicator of reactive oxygen species (ROS) generation. Allopurinol, a xanthine oxidase (XO) inhibitor, diminished the 4-ONE-induced increase in the 2',7'-dichlorofluorescein-fluorescence intensity and the decrease in viability, indicating the role of XO in mediating 4-ONE-induced cell death. These observations suggest that 4-ONE has the potential to induce liver cell death via XO-derived ROS generation. |
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Authors:
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Satoru Sakuma; Miki Negoro; Takahiro Kitamura; Yohko Fujimoto |
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Publication Detail:
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Type: In Vitro; Journal Article Date: 2010-09-15 |
Journal Detail:
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Title: Toxicology and applied pharmacology Volume: 249 ISSN: 1096-0333 ISO Abbreviation: Toxicol. Appl. Pharmacol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-10-26 Completed Date: 2010-11-24 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0416575 Medline TA: Toxicol Appl Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 127-31 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Laboratory of Physiological Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. sakuma@gly.oups.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aldehydes
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toxicity* Animals Apoptosis / drug effects Dose-Response Relationship, Drug Hepatocytes / cytology, drug effects*, metabolism Rats Reactive Oxygen Species / metabolism* Xanthine Oxidase / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/4-oxo-2-nonenal; 0/Aldehydes; 0/Reactive Oxygen Species; 29343-52-0/4-hydroxy-2-nonenal; EC 1.17.3.2/Xanthine Oxidase |
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