Protective effects of resveratrol on ethanol-induced apoptosis in embryonic stem cells and disruption of embryonic development in mouse blastocysts Huang, L -H; Shiao, N -H [Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li 32023, Taiwan (China)]; Hsuuw, Y -D [Department of Life Science, National Pingtung University of Science and Technology, Pingtung, Taiwan (China)]; Chan, W -H [Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li 32023, Taiwan (China)]; R and D Center for Membrane Technology, Chung Yuan Christian University, Taiwan (China)], E-mail: whchan@cycu.edu.tw 60 APPLIED LIFE SCIENCES; ANTIOXIDANTS; APOPTOSIS; CALCIUM IONS; CELL PROLIFERATION; ETHANOL; GRAPES; IN VITRO; IN VIVO; INFLAMMATION; INJURIES; MICE; MITOCHONDRIA; NITRIC OXIDE; ONTOGENESIS; STEM CELLS Previous studies have established that ethanol induces apoptosis, but the precise molecular mechanisms are currently unclear. Here, we show that 0.3-1.0% (w/v) ethanol induces apoptosis in mouse blastocysts and that resveratrol, a grape-derived phytoalexin with known antioxidant and anti-inflammatory properties, prevents ethanol-induced apoptosis and inhibition of cell proliferation. Moreover, ethanol-treated blastocysts show normal levels of implantation on culture dishes in vitro but a reduced ability to reach the later stages of embryonic development. Pretreatment with resveratrol prevented ethanol-induced disruption of embryonic development in vitro and in vivo. In an in vitro cell-based assay, we further found that ethanol increases the production of reactive oxygen species in ESC-B5 embryonic stem cells, leading to an increase in the intracellular concentrations of cytoplasmic free Ca{sup 2+} and NO, loss of mitochondrial membrane potential, mitochondrial release of cytochrome c, activation of caspase-9 and -3, and apoptosis. These changes were blocked by pretreatment with resveratrol. Based on these results, we propose a model for the protective effect of resveratrol on ethanol-induced cell injury in blastocysts and ESC-B5 cells. Available from http://dx.doi.org/10.1016/j.tox.2007.09.015;INIS Ireland 2007-12-05 English Journal Article Journal Name: Toxicology; Journal Volume: 242; Journal Issue: 1-3; Other Information: DOI: 10.1016/j.tox.2007.09.015; PII: S0300-483X(07)00649-X; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA) Medium: X; Size: page(s) 109-122 https://doi.org/10.1016/j.tox.2007.09.015 [] 1-3 242 Journal ID: ISSN 0300-483X; TXCYAC; TRN: IE08R0175061927 INIS 2010-01-01 21042633