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Biochem Biophys Res Commun. 2009 Feb 20;379(4):876-81. doi: 10.1016/j.bbrc.2008.12.133. Epub 2009 Jan 6.

A novel small molecule, LAS-0811, inhibits alcohol-induced apoptosis in VL-17A cells.

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Department of Internal Medicine, Transplant Research Program, University of California Davis Medical Center, 4635 2nd Ave. Research Building I, Room 1001, Sacramento, CA 95817, USA.


One of the pathways by which alcohol induces hepatocyte apoptosis is via oxidative stress. We screened several chemically-synthesized small molecules and found LAS-0811, which inhibits oxidative stress. In this study, we elucidated its role in inhibiting alcohol-induced apoptosis in hepatocyte-like VL-17A cells. VL-17A cells were pre-incubated with LAS-0811, followed by ethanol incubation. Ethanol-induced reactive oxygen species and apoptosis were significantly inhibited in LAS-0811 pre-treated cells. VL-17A cells were transfected with a reporter (ARE/TK-GFP) plasmid containing green fluorescent protein (GFP) as a reporter gene and the anti-oxidant response element as the promoter. LAS-0811 pre-treatment significantly induced the GFP expression compared to the cells treated with ethanol alone. LAS-0811 induced the activation of nrf2 and enhanced the expression and activity of glutathione peroxidase, one of the downstream targets of nrf2. The results indicate that LAS-0811 protects VL-17A cells against ethanol-induced oxidative stress and apoptosis at least in part via nrf2 activation.

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