Journal
TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 249, Issue 2, Pages 127-131Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2010.08.025
Keywords
4-oxo-2-nonenal; 4-Hydroxy-2-nonenal; Cell death; Apoptosis; Hepatocyte
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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 mu M, 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 mu M, 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. (c) 2010 Elsevier Inc. All rights reserved.
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