Document Detail

Xanthine oxidase-derived reactive oxygen species mediate 4-oxo-2-nonenal-induced hepatocyte cell death.
MedLine Citation:
PMID:  20816884     Owner:  NLM     Status:  MEDLINE    
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.
Satoru Sakuma; Miki Negoro; Takahiro Kitamura; Yohko Fujimoto
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Publication Detail:
Type:  In Vitro; Journal Article     Date:  2010-09-15
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  249     ISSN:  1096-0333     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-10-26     Completed Date:  2010-11-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  127-31     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Laboratory of Physiological Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
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MeSH Terms
Aldehydes / toxicity*
Apoptosis / drug effects
Dose-Response Relationship, Drug
Hepatocytes / cytology,  drug effects*,  metabolism
Reactive Oxygen Species / metabolism*
Xanthine Oxidase / metabolism*
Reg. No./Substance:
0/4-oxo-2-nonenal; 0/Aldehydes; 0/Reactive Oxygen Species; 29343-52-0/4-hydroxy-2-nonenal; EC Oxidase

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