Xanthine oxidase-derived reactive oxygen species mediate 4-oxo-2-nonenal-induced hepatocyte cell death.

Satoru Sakuma, Miki Negoro, Takahiro Kitamura, Yohko Fujimoto

Laboratory of Physiological Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. sakuma@gly.oups.ac.jp

Toxicology and applied pharmacology 2010 Dec 1

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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. Copyright © 2010 Elsevier Inc. All rights reserved.

Citation

Satoru Sakuma, Miki Negoro, Takahiro Kitamura, Yohko Fujimoto. Xanthine oxidase-derived reactive oxygen species mediate 4-oxo-2-nonenal-induced hepatocyte cell death. Toxicology and applied pharmacology. 2010 Dec 1;249(2):127-31