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

• Published in: Toxicology and applied pharmacology Vol. 249; no. 2; pp. 127 - 131
• Main Authors: Sakuma, Satoru, Negoro, Miki, Kitamura, Takahiro, Fujimoto, Yohko
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.12.2010; Elsevier
• Subjects: 4-Hydroxy-2-nonenal; 4-Oxo-2-nonenal; 60 APPLIED LIFE SCIENCES; Aldehydes; Aldehydes - toxicity; ANIMAL CELLS; ANIMALS; APOPTOSIS; Apoptosis - drug effects; Biological and medical sciences; Cell death; Dose-Response Relationship, Drug; ELEMENTS; ENZYMES; Hepatocyte; Hepatocytes - cytology; Hepatocytes - drug effects; Hepatocytes - metabolism; In Vitro Techniques; LIVER CELLS; MAMMALS; Medical sciences; NONMETALS; ORGANIC COMPOUNDS; OXIDASES; OXIDOREDUCTASES; OXYGEN; PROTEINS; RATS; Reactive Oxygen Species - metabolism; RODENTS; SOMATIC CELLS; TOXICITY; Toxicology; VERTEBRATES; VIABILITY; Xanthine Oxidase - metabolism; 4-Hydroxy-2-nonenal; 4-Oxo-2-nonenal; Hepatocyte; Cell death; Apoptosis; Oxidative stress; Reactive oxygen species; Digestive system; Enzyme; Liver; Nonenal; In vitro; Xanthine oxidase; Oxidoreductases
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2010.08.025

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.